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Sample records for extract decreased breast

  1. Decreased contralateral breast volume after mastectomy, adjuvant chemotherapy, and anti-estrogen therapy, in particular in breasts with high density.

    PubMed

    Ishii, Naohiro; Ando, Jiro; Harao, Michiko; Takemae, Masaru; Kishi, Kazuo

    2017-10-01

    Adjuvant chemotherapy and anti-estrogenic therapy can result in decreased volume of the contralateral breast, following mastectomy for the treatment of breast cancer. However, no data on the effect of adjuvant therapy on contralateral breast volume have previously been reported. We aimed to evaluate the extent to which adjuvant therapy and differences in breast density contribute to decreased breast volume. We conducted a prospective cohort study, selecting 40 nonconsecutive patients who underwent immediate breast reconstruction with mastectomy and expander insertion followed by expander replacement. We measured the contralateral breast volume before each procedure. The extent of the change was analyzed with respect to adjuvant therapy and breast density measured by preoperative mammography. The greatest decrease in breast volume was 135.1 cm(3). The decrease in breast volume was significantly larger in the adjuvant therapy (+) group, particularly in patients with high breast density, than in the adjuvant therapy (-) group. Significant differences between the chemotherapy (+), tamoxifen (+) group and the chemotherapy (-), tamoxifen (+) group were not found. Breast density scores had a range of 2.0-3.3 (mean: 2.8). In breast reconstruction, particularly when performed in one stage, preoperative mammography findings are valuable to plastic surgeons, and possible decreases in the contralateral breast volume due to adjuvant therapy, particularly in patients with high breast density, should be considered carefully. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  2. Feature Extraction and Analysis of Breast Cancer Specimen

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, Debnath; Robles, Rosslin John; Kim, Tai-Hoon; Bandyopadhyay, Samir Kumar

    In this paper, we propose a method to identify abnormal growth of cells in breast tissue and suggest further pathological test, if necessary. We compare normal breast tissue with malignant invasive breast tissue by a series of image processing steps. Normal ductal epithelial cells and ductal / lobular invasive carcinogenic cells also consider for comparison here in this paper. In fact, features of cancerous breast tissue (invasive) are extracted and analyses with normal breast tissue. We also suggest the breast cancer recognition technique through image processing and prevention by controlling p53 gene mutation to some greater extent.

  3. Mushroom Extracts Decrease Bone Resorption and Improve Bone Formation.

    PubMed

    Erjavec, Igor; Brkljacic, Jelena; Vukicevic, Slobodan; Jakopovic, Boris; Jakopovich, Ivan

    2016-01-01

    Mushroom extracts have shown promising effects in the treatment of cancer and various chronic diseases. Osteoporosis is considered one of the most widespread chronic diseases, for which currently available therapies show mixed results. In this research we investigated the in vitro effects of water extracts of the culinary-medicinal mushrooms Trametes versicolor, Grifola frondosa, Lentinus edodes, and Pleurotus ostreatus on a MC3T3-E1 mouse osteoblast-like cell line, primary rat osteoblasts, and primary rat osteoclasts. In an animal osteoporosis model, rats were ovariectomized and then fed 2 mushroom blends of G. frondosa and L. edodes for 42 days. Bone loss was monitored using densitometry (dual-energy X-ray absorptiometry) and micro computed tomography. In the concentration test, mushroom extracts showed no toxic effect on MC3T3-E1 cells; a dose of 24 µg/mL showed the most proliferative effect. Mushroom extracts of T. versicolor, G. frondosa, and L. edodes inhibited osteoclast activity, whereas the extract of L. edodes increased osteoblast mineralization and the production of osteocalcin, a specific osteoblastic marker. In animals, mushroom extracts did not prevent trabecular bone loss in the long bones. However, we show for the first time that the treatment with a combination of extracts from L. edodes and G. frondosa significantly reduced trabecular bone loss at the lumbar spine. Inhibitory properties of extracts from L. edodes on osteoclasts and the promotion of osteoblasts in vitro, together with the potential to decrease lumbar spine bone loss in an animal osteoporosis model, indicate that medicinal mushroom extracts can be considered as a preventive treatment and/or a supplement to pharmacotherapy to enhance its effectiveness and ameliorate its harmful side effects.

  4. Hypothesis: smoking decreases breast feeding duration by suppressing prolactin secretion.

    PubMed

    Bahadori, Babak; Riediger, Natalie D; Farrell, Sharla M; Uitz, Elisabeth; Moghadasian, Mohammed F

    2013-10-01

    A number of studies, including new data summarized here, conclude that breast feeding duration is lower in smoking mothers. Although some have suggested that this merely reflects poor health motivation in those prone to smoke, several lines of evidence support the view that chronic smoking does indeed compromise breast feeding by suppressing prolactin secretion and thereby lowering breast milk volume. Moreover, a recent clinical trial shows that an effective smoking cessation program can boost breast feeding duration in smokers. An analysis of pertinent rodents studies suggests that chronic nicotine administration boosts dopaminergic activity in the tuberoinfundibular tract which functions to inhibit prolactin release; this increase in dopaminergic activity, in turn, may reflect a nicotine-mediated suppression of hypothalamic opioid activity.

  5. The effect of decreasing maternity leave on breast-feeding patterns.

    PubMed

    Madlon-Kay, D J; Carr, R J

    1988-01-01

    An Army hospital decreased maternity leave for its female soldiers from 42 days to 30 days. For the 12 months preceding the change, 42% of the soldiers chose to breast feed. For the 12 months after the change in maternity leave, 41% of the soldiers chose to breast feed. The decrease in leave had no effect on the duration of breast feeding. Most soldiers before and after the change weaned by the time their infants were two months old.

  6. Broccoli Sprout Extract in Treating Patients With Breast Cancer

    ClinicalTrials.gov

    2017-02-14

    Ductal Breast Carcinoma; Ductal Breast Carcinoma In Situ; Estrogen Receptor Negative; Estrogen Receptor Positive; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Postmenopausal; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

  7. Biomechanics of milk extraction during breast-feeding

    PubMed Central

    Elad, David; Kozlovsky, Pavel; Blum, Omry; Laine, Andrew F.; Po, Ming Jack; Botzer, Eyal; Dollberg, Shaul; Zelicovich, Mabel; Ben Sira, Liat

    2014-01-01

    How do infants extract milk during breast-feeding? We have resolved a century-long scientific controversy, whether it is sucking of the milk by subatmospheric pressure or mouthing of the nipple–areola complex to induce a peristaltic-like extraction mechanism. Breast-feeding is a dynamic process, which requires coupling between periodic motions of the infant’s jaws, undulation of the tongue, and the breast milk ejection reflex. The physical mechanisms executed by the infant have been intriguing topics. We used an objective and dynamic analysis of ultrasound (US) movie clips acquired during breast-feeding to explore the tongue dynamic characteristics. Then, we developed a new 3D biophysical model of the breast and lactiferous tubes that enables the mimicking of dynamic characteristics observed in US imaging during breast-feeding, and thereby, exploration of the biomechanical aspects of breast-feeding. We have shown, for the first time to our knowledge, that latch-on to draw the nipple–areola complex into the infant mouth, as well as milk extraction during breast-feeding, require development of time-varying subatmospheric pressures within the infant’s oral cavity. Analysis of the US movies clearly demonstrated that tongue motility during breast-feeding was fairly periodic. The anterior tongue, which is wedged between the nipple–areola complex and the lower lips, moves as a rigid body with the cycling motion of the mandible, while the posterior section of the tongue undulates in a pattern similar to a propagating peristaltic wave, which is essential for swallowing. PMID:24706845

  8. Biomechanics of milk extraction during breast-feeding.

    PubMed

    Elad, David; Kozlovsky, Pavel; Blum, Omry; Laine, Andrew F; Po, Ming Jack; Botzer, Eyal; Dollberg, Shaul; Zelicovich, Mabel; Ben Sira, Liat

    2014-04-08

    How do infants extract milk during breast-feeding? We have resolved a century-long scientific controversy, whether it is sucking of the milk by subatmospheric pressure or mouthing of the nipple-areola complex to induce a peristaltic-like extraction mechanism. Breast-feeding is a dynamic process, which requires coupling between periodic motions of the infant's jaws, undulation of the tongue, and the breast milk ejection reflex. The physical mechanisms executed by the infant have been intriguing topics. We used an objective and dynamic analysis of ultrasound (US) movie clips acquired during breast-feeding to explore the tongue dynamic characteristics. Then, we developed a new 3D biophysical model of the breast and lactiferous tubes that enables the mimicking of dynamic characteristics observed in US imaging during breast-feeding, and thereby, exploration of the biomechanical aspects of breast-feeding. We have shown, for the first time to our knowledge, that latch-on to draw the nipple-areola complex into the infant mouth, as well as milk extraction during breast-feeding, require development of time-varying subatmospheric pressures within the infant's oral cavity. Analysis of the US movies clearly demonstrated that tongue motility during breast-feeding was fairly periodic. The anterior tongue, which is wedged between the nipple-areola complex and the lower lips, moves as a rigid body with the cycling motion of the mandible, while the posterior section of the tongue undulates in a pattern similar to a propagating peristaltic wave, which is essential for swallowing.

  9. Do statins increase and Mediterranean diet decrease the risk of breast cancer?

    PubMed Central

    2014-01-01

    Background Physical exercise and healthy dietary habits are recommended to prevent breast cancer. Discussion Increased intake of omega-3 fatty acids associated with decreased omega-6 - resulting in higher omega-3 to omega-6 ratio compared with Western-type diet - is inversely associated with breast cancer risk. The modernized Mediterranean diet with high omega-3 to omega-6 ratio, high fiber and polyphenol intake, and consumption of low-glycemic index foods reduces overall cancer risk and specifically breast cancer risk. It has been suggested that consuming no more than one alcoholic drink per day, preferably wine, is preferable. Eliminating environmental contaminants, including endocrine disruptors, and favoring organic foods to increase polyphenol intake and the omega-3 to omega-6 ratios were also shown to be beneficial. Cholesterol-lowering statins may decrease antitumor defenses; are toxic for the mitochondria; decrease the omega-3 to omega-6 ratio; increase body mass index, insulin resistance and diabetic risk; and have been associated with an increased breast cancer risk. Summary Therefore, as well as making lifestyle changes to decrease breast cancer risk, we argue that physicians should carefully consider (and often avoid) therapies that may increase breast cancer or diabetes risk in high-risk women and women who wish to decrease their breast cancer risk. PMID:24903828

  10. The effect of decreased caffeine consumption on benign proliferative breast disease: a randomized clinical trial.

    PubMed

    Allen, S S; Froberg, D G

    1987-06-01

    A single-blind, randomized clinical trial of 56 female subjects was conducted to determine whether decreased consumption of caffeine decreases breast pain/tenderness or nodularity in patients with suspected benign proliferative breast disease. The subjects were randomly assigned to one of three groups--a control group (no dietary restrictions), a placebo group (cholesterol-free diet), and an experimental group (caffeine-free diet). At the initial examination, the subjects reported on the presence of breast pain, the degree to which pain affects daily activities, the frequency of pain, the degree of pain associated with breast examinations, and the degree of pain associated with close-fitting clothing. Subjects were then examined and the four quadrants of each breast were rated on a scale of 0 to 3 (0 = normal, fatty tissue, 1 = little seedy bumps or fine nodularity, 2 = discrete nodules or ropy tissue, 3 = confluent areas, hard or soft masses). Subjects in all three groups returned for 2- and 4-month follow-up examinations. Total nodularity scores, degree of pain/tenderness, and compliance with dietary restrictions were analyzed. The data showed that decreased caffeine consumption did not result in a significant reduction of palpable breast nodules or in a lessening of breast pain/tenderness.

  11. Feature extraction via composite scoring and voting in breast cancer.

    PubMed

    Koch, Martin; Hanl, Markus; Wiese, Michael

    2012-08-01

    Identification and characterization of tumor subtypes using gene expression profiles of triple negative breast cancer patients. Microarray data of four breast cancer studies were pooled and evaluated. Molecular subtype classification was performed using random forest and a novel algorithm for feature extraction via composite scoring and voting. Biological and clinical properties were evaluated via GSEA, functional annotation clustering and clinical endpoint analysis. The subtype signatures are highly predictive for distant metastasis free survival of tamoxifen-treated patients. Consensus clustering and the novel algorithm proposed three triple negative subtypes. One subtype shows low E2F4 gene expression and is predictive for survival of ER negative breast cancer patients. The other two subtypes share commonalities with luminal B tumors. Classification of breast cancer expression profiles may reveal novel tumor subtypes, possessing clinical impact. Furthermore, subtype characterizing gene signatures might hold potential for novel strategies in cancer therapy.

  12. Mechanism of cytotoxicity by Psoralea corylifolia extract in human breast carcinoma cells.

    PubMed

    Rajan, Vasumathy; Tripathi, Jyoti; Variyar, Prasad; Pandey, Badri Narain

    2014-01-01

    Psoralea corylifolia has been widely used in herbal medicine, and a few studies show its anticancer activity. However, the detailed mechanism of the anticancer activity of P. corylifolia seed extract (PC extract) was not studied. This study evaluates the anticancer activity and underlying mechanism of PC extract in a human breast cancer cell line (MCF7). PC extract caused a concentration-dependent decrease in the proliferation of MCF7 cells and an increase in apoptotic death as measured by annexin-V-FITC and TUNEL assays. Increased cleavage of poly(ADP-ribose) polymerase in cells treated with PC extract further confirmed the apoptotic mode of cell death. There was a decrease (~2-fold) of mitochondrial membrane potential in cells treated with PC extract. In cells treated with PC extract, an increase in intracellular reactive oxygen species (ROS) and a decrease in mitochondrial ROS was observed. A significant decrease in ATP (~1.8-fold) was observed in extract-treated cells. Moreover, MCF7 cells treated with extract showed cleavage of caspase-9 and caspase-7, upregulation of Bax, release of cytochrome-c, and loss of mitochondrial integrity. Taken together, these results suggest the involvement of the mitochondrial pathway in PC extract-induced apoptosis in MCF7 cells.

  13. Fiber purified extracts of carob fruit decrease carbohydrate absorption.

    PubMed

    Macho-González, A; Garcimartín, A; López-Oliva, M E; Bertocco, G; Naes, F; Bastida, S; Sánchez-Muniz, F J; Benedí, J

    2017-06-21

    The postprandial state plays a central role in the development and setting of chronic diseases. Condensed tannins (CT) are polyphenols with a known ability to modify carbohydrate digestion and absorption. The high concentration of CT in the pulp of carob fruit suggests a potential antidiabetic effect. The aim of this work was to analyze the in vitro and in vivo effects of carob fruit extract (CFE) on the digestion and absorption of carbohydrates. α-Glucosidase activity and glucose diffusion were tested in vitro using 0.5, 1, 2 and 5 mg mL(-1) CFE concentrations. Two in vivo absorption studies, acute and subchronic, were carried out in four groups of 6 two-month-old male Wistar rats (control and CFE 25, 50 and 150 mg per kg b.w.), administering 1 mL of olive oil and 0.5 g per kg b.w. of glucose solution by oral gavage. CFE significantly inhibited α-glucosidase activity, through a competitive mechanism, from 1 mg mL(-1), and also reduced glucose diffusion in a dose-dependent manner. In the acute study, CFE (50 and 150 mg per kg b.w.) significantly reduced the area under the curve (AUC) of blood glucose. Subchronic CFE administration induced further AUC decreases; and CFE at 150 mg per kg b.w. reduced sodium-glucose-linked transporter-1 (SGLT1) levels in the duodenum. This study demonstrates the hypoglycemic properties of CFE, highlighting its potential role as a suitable nutritional strategy in diabetic patients.

  14. Apoptosis-mediated inhibition of human breast cancer cell proliferation by lemon citrus extract.

    PubMed

    Alshatwi, Ali A; Shafi, Gowhar; Hasan, Tarique N; Al-Hazzani, Amal A; Alsaif, Mohammed A; Alfawaz, Mohammed A; Lei, K Y; Munshi, Anjana

    2011-01-01

    Dietary phytochemicals have a variety of antitumor properties. In the present study, the antitumor activity of methanolic extract of lemon fruit (lemon extract; LE) (LE) on the MCF-7 breast cancer cell line was investigated in vitro. Apoptotic cell death was analyzed using the TUNEL assay. In addition, the apoptosis mediated by LE extract in the MCF-7 cells was associated with the increased expression of the tumor suppressor p53 and caspase-3. Additionally, the expression of a pro-apoptotic gene, bax, was increased, and the expression of an anti-apoptotic gene, bcl-2, was decreased by LE extract treatment, resulting in a shift in the Bax:Bcl-2 ratio to one that favored apoptosis. The expression of a major apoptotic gene, caspase-3, was increased by LE extract treatment. In light of the above results, we concluded that LE extract can induce the apoptosis of MCF-7 breast cancer cells via Bax-related caspase-3 activation. This study provides experimental data that are relevant to the possible future clinical use of LE to treat breast cancer.

  15. Decreased expression of ADAMTS-1 in human breast tumors stimulates migration and invasion

    PubMed Central

    2013-01-01

    Background ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin motifs) is a member of the ADAMTS family of metalloproteases. Here, we investigated mRNA and protein levels of ADAMTS-1 in normal and neoplastic tissues using qPCR, immunohistochemistry and immunoblot analyses, and we addressed the role of ADAMTS-1 in regulating migration, invasion and invadopodia formation in breast tumor cell lines. Results In a series of primary breast tumors, we observed variable levels of ADAMTS-1 mRNA expression but lower levels of ADAMTS-1 protein expression in human breast cancers as compared to normal tissue, with a striking decrease observed in high-malignancy cases (triple-negative for estrogen, progesterone and Her-2). This result prompted us to analyze the effect of ADAMTS-1 knockdown in breast cancer cells in vitro. MDA-MB-231 cells with depleted ADAMTS-1 expression demonstrated increased migration, invasion and invadopodia formation. The regulatory mechanisms underlying the effects of ADAMTS-1 may be related to VEGF, a growth factor involved in migration and invasion. MDA-MB-231 cells with depleted ADAMTS-1 showed increased VEGF concentrations in conditioned medium capable of inducing human endothelial cells (HUVEC) tubulogenesis. Furthermore, expression of the VEGF receptor (VEGFR2) was increased in MDA-MB-231 cells as compared to MCF7 cells. To further determine the relationship between ADAMTS-1 and VEGF regulating breast cancer cells, MDA-MB-231 cells with reduced expression of ADAMTS-1 were pretreated with a function-blocking antibody against VEGF and then tested in migration and invasion assays; both were partially rescued to control levels. Conclusions ADAMTS-1 expression was decreased in human breast tumors, and ADAMTS-1 knockdown stimulated migration, invasion and invadopodia formation in breast cancer cells in vitro. Therefore, this series of experiments suggests that VEGF is involved in the effects mediated by ADAMTS-1 in breast cancer cells. PMID

  16. Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine.

    PubMed

    Huang, Jianbo; Jin, Liangbin; Ji, Guangyan; Xing, Lei; Xu, Chaobo; Xiong, Xiong; Li, Hongyuan; Wu, Kainan; Ren, Guosheng; Kong, Lingquan

    2013-07-06

    Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using higher dose of T3 together

  17. Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

    PubMed Central

    2013-01-01

    Background Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. Methods Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. Results In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using

  18. Antiproliferatory Effects of Crab Shell Extract on Breast Cancer Cell Line (MCF7)

    PubMed Central

    Rezakhani, Leila; Rashidi, Zahra; Mirzapur, Pegah

    2014-01-01

    Purpose Breast cancer is the most common type of cancer in women. Despite various pharmacological developments, the identification of new therapies is still required for treating breast cancer. Crab is often recommended as a traditional medicine for cancer. This study aimed to determine the in vitro effect of a hydroalcoholic crab shell extract on a breast cancer cell line. Methods In this experimental study, MCF7 breast cancer cell line was used. Crab shell was powdered and a hydroalcoholic (70° ethanol) extract was prepared. Five concentrations (100, 200, 400, 800, and 1,000 µg/mL) were added to the cells for three periods, 24, 48, and 72 hours. The viability of the cells were evaluated using trypan blue and 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. Cell apoptosis was determined using the terminal deoxynucleotidyl transferase dUTP nick end labeling method. Nitric oxide (NO) level was assessed using the Griess method. Data were analyzed using analysis of variance, and p<0.05 was considered significant. Results Cell viability decreased depending on dose and time, and was significantly different in the groups that were treated with 400, 800, and 1,000 µg/mL doses compared to that in the control group (p<0.001). Increasing the dose significantly increased apoptosis (p<0.001). NO secretion from MCF7 cells significantly decreased in response to different concentrations of the extract in a dose- and time-dependent manner (p<0.050). Conclusion The crab shell extract inhibited the proliferation of MCF7 cells by increasing apoptosis and decreasing NO production. PMID:25320619

  19. Satellite cell-mediated breast muscle regeneration decreases with broiler size.

    PubMed

    Daughtry, M R; Berio, E; Shen, Z; Suess, E J R; Shah, N; Geiger, A E; Berguson, E R; Dalloul, R A; Persia, M E; Shi, H; Gerrard, D E

    2017-09-01

    Satellite cells (SCs) reside between the sarcolemma and basal lamina of muscle fibers and are the primary contributor of DNA for post-hatch muscle growth and repair. Alterations in SC content or properties by intrinsic and extrinsic factors can have detrimental effects on muscle health and function, and ultimately meat quality. We hypothesized that disrupted SC homeostasis may account in part for the increased breast myopathies observed in growing broilers. To test this hypothesis, we selected broilers with different body weights at comparable ages and studied SC characteristics in vitro and in vivo. Data shows that SC numbers in the breast muscles decrease (P < 0.001) and their inherent abilities to proliferate and differentiate diminish (P < 0.001) with age and size. Further, when breast muscle is presented with an insult, muscle of larger broilers regenerates more slowly than their smaller, age-matched counterparts arguing that SC quality changes with size and age. Together, our studies show that birds with greater muscle hypertrophy have less SCs with diminished ability to function, and suggest that aggressive selection for breast growth in broilers may exhaust SC pools when birds are grown to heavier processing weights. These findings provide new insights into a possible mechanism leading to breast myopathies in the poultry industry and provide targets for mitigating adverse fresh breast quality. © 2017 Poultry Science Association Inc.

  20. Adherence to Needed Adjuvant Therapy Could Decrease Recurrence Rates for Rural Patients With Early Breast Cancer.

    PubMed

    Xuan, Qijia; Gao, Kun; Song, Ying; Zhao, Shu; Dong, Lina; Zhang, Zhongbai; Zhang, Qingyuan; Wang, Jingxuan

    2016-12-01

    The purpose of this study was to evaluate the differences in stage upon diagnosis, adherence to adjuvant treatment, and recurrence between rural and urban patients with early breast cancer. This retrospective study included 3640 patients with primary breast cancer recruited from 2000 to 2009. Patients who developed recurrence or metastasis were verified by adequate diagnostic imaging modalities and pathology. The χ(2) test was used to compare groups with respect to variables (recurrence and clinicopathologic features). A multivariable Cox proportional hazard regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for breast cancer recurrence risk. Compared with tumors in urban patients, those in rural patients showed higher histologic grade, larger size, more lymphatic metastasis, and higher Ki-67 index; therapy adherence was strongly associated with recurrence in both. Compared with urban patients, the female rural patients had a higher recurrence rate. However, no significant difference in recurrence rates was observed between urban and rural patients following guideline adherence. The results of our study suggest that the later stage upon diagnosis and nonadherence to treatment contribute toward worse breast cancer outcomes among rural patients with breast cancer. Adherence to needed adjuvant therapy could decrease recurrence rates for rural patients with early breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Decreased expression of SOX17 is associated with tumor progression and poor prognosis in breast cancer.

    PubMed

    Fu, De-Yuan; Tan, Hao-Sheng; Wei, Jin-Li; Zhu, Chang-Ren; Jiang, Ji-Xin; Zhu, Yu-Xiang; Cai, Feng-Lin; Chong, Mei-Hong; Ren, Chuan-Li

    2015-09-01

    The SOX17 (SRY-related HMG-box) transcription factor is involved in a variety of biological processes and is related to the tumorigenesis and progression of multiple tumors. However, the clinical application of SOX17 for breast cancer prognosis is currently limited. The aim of this study was to investigate the clinicopathologic and prognostic significance of SOX17 expression in human breast cancer. qPCR and western blot assays were performed to measure the expression of SOX17 in breast cancer cell lines and 30 matched pairs of breast cancer and corresponding noncancerous tissues. A SOX17 overexpression cell model was used to examine changes in cell growth in vitro. Immunohistochemical analyses were performed to retrospectively examine the prognostic impact of SOX17 expression in 187 additional breast cancer patients. Our results showed that SOX17 expression was decreased at both the messenger RNA (mRNA) and protein levels in the breast cancer cell lines and tissues, and that SOX17 overexpression could strongly suppress cell growth in vitro. Furthermore, the lack of SOX17 protein expression was strongly correlated with higher tumor grade (P = 0.002), lymph node metastasis (P < 0.001), and tumor node metastasis (TNM) stage (P = 0.001) and had poorer disease-free survival (DFS) and overall survival (OS) compared to normal SOX17 expression (P = 0.002 and 0.001, respectively). Univariate and multivariate analyses indicated that lower SOX17 expression was an independent prognostic factor for DFS (P = 0.007; HR = 2.854; 95 % CI 1.326-6.147) and OS (P = 0.005; HR = 5.035; 95 % CI 1.648-15.385) for breast cancer. Our findings indicate that SOX17 expression is a useful prognostic biomarker for breast cancer.

  2. MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer.

    PubMed

    Huo, Lei; Wang, Yan; Gong, Yun; Krishnamurthy, Savitri; Wang, Jing; Diao, Lixia; Liu, Chang-Gong; Liu, Xiuping; Lin, Feng; Symmans, William F; Wei, Wei; Zhang, Xinna; Sun, Li; Alvarez, Ricardo H; Ueno, Naoto T; Fouad, Tamer M; Harano, Kenichi; Debeb, Bisrat G; Wu, Yun; Reuben, James; Cristofanilli, Massimo; Zuo, Zhuang

    2016-04-01

    Inflammatory breast cancer is the most aggressive form of breast cancer. Identifying new biomarkers to be used as therapeutic targets is in urgent need. Messenger RNA expression profiling studies have indicated that inflammatory breast cancer is a transcriptionally heterogeneous disease, and specific molecular targets for inflammatory breast cancer have not been well established. We performed microRNA expression profiling in inflammatory breast cancer in comparison with locally advanced noninflammatory breast cancer in this study. Although many microRNAs were differentially expressed between normal breast tissue and tumor tissue, most of them did not show differential expression between inflammatory and noninflammatory tumor samples. However, by microarray analysis, quantitative reverse transcription PCR, and in situ hybridization, we showed that microRNA-205 expression was decreased not only in tumor compared with normal breast tissue, but also in inflammatory breast cancer compared with noninflammatory breast cancer. Lower expression of microRNA-205 correlated with worse distant metastasis-free survival and overall survival in our cohort. A small-scale immunohistochemistry analysis showed coexistence of decreased microRNA-205 expression and decreased E-cadherin expression in some ductal tumors. MicroRNA-205 may serve as a therapeutic target in advanced breast cancer including inflammatory breast cancer.

  3. Huaier extract suppresses breast cancer via regulating tumor-associated macrophages

    PubMed Central

    Li, Yaming; Qi, Wenwen; Song, Xiaojin; Lv, Shangge; Zhang, Hanwen; Yang, Qifeng

    2016-01-01

    Macrophages in tumor microenvironment are mostly M2-polarized - and have been reported to promote tumorigenesis, which are also defined as tumor-associated macrophages (TAMs). Here, we examined the regulatory effects of Huaier extract on TAMs using RAW264.7 murine macrophage cell line. Our data demonstrated that Huaier extract could inhibit the infiltration of macrophages into tumor microenvironment in a dose-dependent manner. By performing RT-PCR, immunofluorescence and phagocytosis assay, we were able to find that Huaier extract could regulate the polarization of macrophages, with decreased M2-polarization and increased phagocytosis of RAW264.7 cells. Moreover, we identified that Huaier extract could suppress macrophages-induced angiogenesis by using HUVEC migration assay, tube formation and chorioallantoic membrane assay. Additionally, western blotting showed decreased expression of MMP2, MMP9 and VEGF with the use of Huaier extract. Finally, we found that Huaier extract could inhibit M2-macrophages infiltration and angiogenesis through treating 4T1 tumor bearing mice with Huaier extract. Our study revealed a novel mechanism of the anti-tumor effect of Huaier extract which inhibited angiogenesis by targeting TAMs. These findings provided that Huaier was a promising drug for clinical treatment of breast cancer. PMID:26831282

  4. DHEA increases epithelial markers and decreases mesenchymal proteins in breast cancer cells and reduces xenograft growth.

    PubMed

    Colín-Val, Zaira; González-Puertos, Viridiana Yazmín; Mendoza-Milla, Criselda; Gómez, Erika Olivia; Huesca-Gómez, Claudia; López-Marure, Rebeca

    2017-10-15

    Breast cancer is one of the most common neoplasias and the leading cause of cancer death in women worldwide. Its high mortality rate is linked to a great metastatic capacity associated with the epithelial-mesenchymal transition (EMT). During this process, a decrease in epithelial proteins expression and an increase of mesenchymal proteins are observed. On the other hand, it has been shown that dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, inhibits migration of breast cancer cells; however, the underlying mechanisms have not been elucidated. In this study, the in vitro effect of DHEA on the expression pattern of some EMT-related proteins, such as E-cadherin (epithelial), N-cadherin, vimentin and Snail (mesenchymal) was measured by Western blot and immunofluorescence in MDA-MB-231 breast cancer cells with invasive, metastatic and mesenchymal phenotype. Also, the in vivo effect of DHEA on xenograft tumor growth in nude mice (nu(-)/nu(-)) and on expression of the same epithelial and mesenchymal proteins in generated tumors was evaluated. We found that DHEA increased expression of E-cadherin and decreased N-cadherin, vimentin and Snail expression both in MD-MB-231 cells and in the formed tumors, possibly by DHEA-induced reversion of mesenchymal phenotype. These results were correlated with a tumor size reduction in mouse xenografts following DHEA administration either a week earlier or concurrent with breast cancer cells inoculation. In conclusion, DHEA could be useful in the treatment of breast cancer with mesenchymal phenotype. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.

    PubMed

    Erin, Nuray; Duymuş, Ozlem; Oztürk, Saffet; Demir, Necdet

    2012-11-10

    Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod.

  6. Human chorionic gonadotropin decreases human breast cancer cell proliferation and promotes differentiation.

    PubMed

    Liao, Xing-Hua; Wang, Yue; Wang, Nan; Yan, Ting-Bao; Xing, Wen-Jing; Zheng, Li; Zhao, Dong-Wei; Li, Yan-Qi; Liu, Long-Yue; Sun, Xue-Guang; Hu, Peng; Zhang, Tong-Cun

    2014-05-01

    Human chorionic gonadotropin (hCG) is a glycoprotein produced by placental trophoblasts. Previous studies indicated that hCG could be responsible for the pregnancy-induced protection against breast cancer in women. It is reported that hCG decreases proliferation and invasion of breast cancer MCF-7 cells. Our research also demonstrates that hCG can reduce the proliferation of MCF-7 cells by downregulating the expression of proliferation markers, proliferating cell nuclear antigen (PCNA), and proliferation-related Ki-67 antigen (Ki-67). Interestingly, we find here that hCG elevates the state of cellular differentiation, as characterized by the upregulation of differentiation markers, β-casein, cytokeratin-18 (CK-18), and E-cadherin. Inhibition of hCG secretion or luteinizing hormone/hCG receptors (LH/hCGRs) synthesis can weaken the effect of hCG on the induction of cell differentiation. Furthermore, hCG can suppress the expression of estrogen receptor alpha. hCG activated receptor-mediated cyclic adenosine monophosphate/protein kinase A signaling pathway. These findings indicated that a protective effect of hCG against breast cancer may be associated with its growth inhibitory and differentiation induction function in breast cancer cells.

  7. Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer.

    PubMed

    Simone, Brittany A; Dan, Tu; Palagani, Ajay; Jin, Lianjin; Han, Sunny Y; Wright, Christopher; Savage, Jason E; Gitman, Robert; Lim, Meng Kieng; Palazzo, Juan; Mehta, Minesh P; Simone, Nicole L

    2016-09-01

    Metastatic breast cancer is devastating and triple negative breast cancers (TNBC) have a higher propensity for metastasis. Improved local control upfront in this aggressive cancer could potentially decrease its propensity toward metastasis. We sought to determine if using caloric restriction (CR) as a systemic therapy, combined with radiation therapy (IR) to the primary tumor, may impact metastatic disease. An orthotopic mouse model using a highly metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable tumors. Mice were then treated with CR, IR, and a combination of the two. In vivo imaging was performed for metastatic evaluation. Molecular evaluation of the tumors was performed, generating a mechanistic hypothesis for CR, which was then tested with pertinent pathway inhibition in the model. CR significantly increased the time to developing metastases, decreased the overall number and volume of lung metastases, and increased survival. CR decreased proliferation, increased apoptosis and globally downregulated the IGF-1R signaling pathway. Adding an IGF-1R/INSR inhibitor to local IR in vivo accomplished a decrease in metastases similar to CR plus IR, demonstrating the importance of the IGF-1R signaling pathway, and underscoring it as a possible mechanism for CR. CR decreased metastatic burden and therefore may complement cytotoxic therapies being used in the clinical setting for metastatic disease. Downregulation of the IGF-1R pathway, is in part responsible for this response and modulating IGF-1R directly resulted in similar improved progression-free survival. The novel use of CR has the potential to enhance clinical outcomes for patients with metastatic breast cancer.

  8. Caloric restriction coupled with radiation decreases metastatic burden in triple negative breast cancer

    PubMed Central

    Simone, Brittany A.; Dan, Tu; Palagani, Ajay; Jin, Lianjin; Han, Sunny Y.; Wright, Christopher; Savage, Jason E.; Gitman, Robert; Lim, Meng Kieng; Palazzo, Juan; Mehta, Minesh P.; Simone, Nicole L.

    2016-01-01

    ABSTRACT Purpose: Metastatic breast cancer is devastating and triple negative breast cancers (TNBC) have a higher propensity for metastasis. Improved local control upfront in this aggressive cancer could potentially decrease its propensity toward metastasis. We sought to determine if using caloric restriction (CR) as a systemic therapy, combined with radiation therapy (IR) to the primary tumor, may impact metastatic disease. Methods: An orthotopic mouse model using a highly metastatic, luciferase-tagged TNBC cell line (4T1), was used to generate palpable tumors. Mice were then treated with CR, IR, and a combination of the two. In vivo imaging was performed for metastatic evaluation. Molecular evaluation of the tumors was performed, generating a mechanistic hypothesis for CR, which was then tested with pertinent pathway inhibition in the model. Results: CR significantly increased the time to developing metastases, decreased the overall number and volume of lung metastases, and increased survival. CR decreased proliferation, increased apoptosis and globally downregulated the IGF-1R signaling pathway. Adding an IGF-1R/INSR inhibitor to local IR in vivo accomplished a decrease in metastases similar to CR plus IR, demonstrating the importance of the IGF-1R signaling pathway, and underscoring it as a possible mechanism for CR. Conclusions: CR decreased metastatic burden and therefore may complement cytotoxic therapies being used in the clinical setting for metastatic disease. Downregulation of the IGF-1R pathway, is in part responsible for this response and modulating IGF-1R directly resulted in similar improved progression-free survival. The novel use of CR has the potential to enhance clinical outcomes for patients with metastatic breast cancer. PMID:27027731

  9. Poly-lactic-glycolic-acid surface nanotopographies selectively decrease breast adenocarcinoma cell functions

    NASA Astrophysics Data System (ADS)

    Zhang, Lijuan; Webster, Thomas J.

    2012-04-01

    The ability of poly(lactic-co-glycolic acid) (PLGA, 50:50 PLG/PGA, wt%) nanotopographies to decrease lung epithelial carcinoma cell functions (including adhesion, proliferation, apoptosis and vascular endothelial growth factor (VEGF) secretion) has been previously reported. Specifically, results demonstrated decreased lung epithelial carcinoma cell VEGF synthesis on 23 nm surface-featured PLGA compared to traditional nanosmooth PLGA. However, clearly, different cell lines could have different behaviors on similar biomaterials. Thus, to investigate the universality of nanopatterned PLGA substrates to inhibit numerous cancer cell functions, here, breast epithelial adenocarcinoma cell (MCF-7) adhesion, proliferation, apoptosis and VEGF secretion were determined on different PLGA nanometer surface topographies. To isolate surface nanotopographical effects from all other surface properties, PLGA surfaces with various nanotopographies but similar chemistry and hydrophobicity were fabricated here. Atomic force microscopy (AFM) verified the varied nanotopographies on the PLGA surfaces prepared in this study. Importantly, results demonstrated for the first time significantly decreased breast adenocarcinoma cell functions (including decreased proliferation rate, increased apoptosis and decreased VEGF synthesis) on 23 nm featured PLGA surfaces compared to all other PLGA surface topographies fabricated (specifically, nanosmooth, 300 and 400 nm surface-featured PLGA surfaces). In contrast, healthy breast epithelial cells proliferated more (24%) on the 23 nm featured PLGA surfaces compared to all other PLGA samples. In summary, these results provided further insights into understanding the role PLGA surface nanotopographies can have on cancer cell functions and, more importantly, open the possibility of using polymer nanotopographies for a wide range of anticancer regenerative medicine applications (without resorting to the use of chemotherapeutics).

  10. Pomegranate fruit extract impairs invasion and motility in human breast cancer.

    PubMed

    Khan, Gazala N; Gorin, Michael A; Rosenthal, Devin; Pan, Quintin; Bao, Li Wei; Wu, Zhi Fen; Newman, Robert A; Pawlus, Alison D; Yang, Peiying; Lansky, Ephraim P; Merajver, Sofia D

    2009-09-01

    Pomegranate fruit extracts (PFEs) possess polyphenolic and other compounds with antiproliferative, pro-apoptotic and anti-inflammatory effects in prostate, lung, and other cancers. Because nuclear transcription factor-kB (NF-kB) is known to regulate cell survival, proliferation, tumorigenesis, and inflammation, it was postulated that PFEs may exert anticancer effects at least in part by modulating NF-kB activity. The authors investigated the effect of a novel, defined PFE consisting of both fermented juice and seed oil on the NF-kB pathway, which is constitutively active in aggressive breast cancer cell lines. The effects of the PFE on NF-kB-regulated cellular processes such as cell survival, proliferation, and invasion were also examined. Analytical characterization of the bioactive components of the PFE revealed active constituents, mainly ellagitannins and phenolic acids in the aqueous PFE and conjugated octadecatrienoic acids in the lipid PFE derived from seeds.The aqueous PFE dose-dependently inhibited NF-kB-dependent reporter gene expression associated with proliferation, invasion, and motility in aggressive breast cancer phenotypes while decreasing RhoC and RhoA protein expression. Inhibition of motility and invasion by PFEs, coincident with suppressed RhoC and RhoA protein expression, suggests a role for these defined extracts in lowering the metastatic potential of aggressive breast cancer species.

  11. Decreased Expression of the Early Mitotic Gene CHFR Contributes to the Acquisition of Breast Cancer Phenotypes

    DTIC Science & Technology

    2007-03-01

    human model system. To characterize the role of CHFR in breast cancer , we used both cultured breast cell lines... epithelial cells became elongated and showed more variability in cell size, which is suggestive of the epithelial -to- mesenchymal transition that is...was to characterize the role of CHFR in breast cancer tumorigenesis using both cultured breast cancer cell lines and primary breast cancers

  12. Anticancer Effects of Extracts from the Fruit of Morinda Citrifolia (Noni) in Breast Cancer Cell Lines.

    PubMed

    Sharma, K; Pachauri, S D; Khandelwal, K; Ahmad, H; Arya, A; Biala, P; Agrawal, S; Pandey, R R; Srivastava, A; Srivastav, A; Saxena, J K; Dwivedi, A K

    2016-03-01

    Morinda citrifolia L. (NONI) fruits have been used for thousands of years for the treatment of many health problems including cancer, cold, diabetes, flu, hypertension, and pain. Plant extracts have reported several therapeutic benefits, but extraction of individual compound from the extract often exhibits limited clinical utility as the synergistic effect of various natural ingredients gets lost. They generally constitute polyphenols and flavonoids. Studies have suggested that these phytochemicals, especially polyphenols, display high antioxidant properties, which help to reduce the risk of degenerative diseases, such as cancer and cardiovascular diseases. Several in-vitro and in-vivo studies have shown that Noni fruits have antioxidant, anti-inflammatory, anti-dementia, liver-protective, anticancer, analgesic, and immunomodulatory effects. Till date about 7 in vitro cancer studies have been done, but a detailed in vitro study including cell cycle and caspase activation assay on breast cancer cell line has not been done. In the present study different Noni fruit fractions have tested on cancer cell lines MCF-7, MDA-MB-231 (breast adenocarcinoma) and one non-cancer cell line HEK-293 (Human embryonic kidney). Out of which ethylacetate extract showed a higher order of in vitro anticancer activity profile. The ethylacetate extract strongly inhibited the proliferation of MCF-7, MDA-MB-231 and HEK-293 cell lines with IC50 values of 25, 35, 60 µg/ml respectively. The extract showed increase in apoptotic cells in MCF-7 and MDA-MB-231 cells and arrested the cell cycle in the G1/S phase in MCF-7 and G0/G1 phase in MDA-MB-231 cells. Noni extract also decreases the intracellular ROS generation and mitochondrial membrane potential. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Anticancer effect of ethanol Lycium barbarum (Goji berry) extract on human breast cancer T47D cell line.

    PubMed

    Wawruszak, Anna; Czerwonka, Arkadiusz; Okła, Karolina; Rzeski, Wojciech

    2016-09-01

    The anticancer activity of ethanol extract isolated from Goji berry (EEGB) on T47D human breast cancer cell line has been reported. Cell viability and cell proliferation were examined with the use of BrdU, MTT and NR methods. Induction of apoptosis was assessed by propidium iodide and Hoechst 33342 staining. Expression of genes involved in cell proliferation, apoptosis, cell cycle control and regulation of transcription was estimated using Western blotting analysis. EEGB inhibited the proliferation of breast cancer cells in a time-, and dose-dependent manner. The study confirmed the lack of EEGB cytotoxic activity to normal human skin fibroblasts. Western blot analysis demonstrated an increase in pro-apoptotic and a decrease in anti-apoptotic proteins' expression in cells treated with the extract. Anticancer activity and lack of toxicity against normal cells indicate a chemopreventive potential of Goji berries in breast cancer treatment.

  14. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer

    PubMed Central

    Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A.; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T.; Aguilera, Renato J.; Dickerson, Erin B.; Torabi, Alireza; Dwivedi, Alok K.; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A.; Nahleh, Zeina

    2017-01-01

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation. PMID:28031536

  15. Use of non-selective β-blockers is associated with decreased tumor proliferative indices in early stage breast cancer.

    PubMed

    Montoya, Alexa; Amaya, Clarissa N; Belmont, Andres; Diab, Nabih; Trevino, Richard; Villanueva, Geri; Rains, Steven; Sanchez, Luis A; Badri, Nabeel; Otoukesh, Salman; Khammanivong, Ali; Liss, Danielle; Baca, Sarah T; Aguilera, Renato J; Dickerson, Erin B; Torabi, Alireza; Dwivedi, Alok K; Abbas, Aamer; Chambers, Karinn; Bryan, Brad A; Nahleh, Zeina

    2017-01-24

    Previous studies suggest beta-adrenergic receptor (β-AR) antagonists (β-blockers) decrease breast cancer progression, tumor metastasis, and patient mortality; however the mechanism for this is unknown. Immunohistochemical analysis of normal and malignant breast tissue revealed overexpression of β1-AR and β3-AR in breast cancer. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor proliferation. Our analysis revealed that non-selective β-blockers, but not selective β-blockers, reduced tumor proliferation by 66% (p < 0.0001) in early stage breast cancer compared to non-users. We tested the efficacy of propranolol on an early stage breast cancer patient, and quantified the tumor proliferative index before and after treatment, revealing a propranolol-mediated 23% reduction (p = 0.02) in Ki67 positive tumor cells over a three-week period. The anti-proliferative effects of β-blockers were measured in a panel of breast cancer lines, demonstrating that mammary epithelial cells were resistant to propranolol, and that most breast cancer cell lines displayed dose dependent viability decreases following treatment. Selective β-blockers alone or in combination were not as effective as propranolol at reducing breast cancer cell proliferation. Molecular analysis revealed that propranolol treatment of the SK-BR-3 breast cancer line, which showed high sensitivity to beta blockade, led to a reduction in Ki67 protein expression, decreased phosphorylation of the mitogenic signaling regulators p44/42 MAPK, p38 MAPK, JNK, and CREB, increased phosphorylation of the cell survival/apoptosis regulators AKT, p53, and GSK3β. In conclusion, use of non-selective β-blockers in patients with early stage breast cancer may lead to decreased tumor proliferation.

  16. Breast-feeding decreases the risk of sporadic salmonellosis among infants in FoodNet sites.

    PubMed

    Rowe, Samantha Y; Rocourt, Jocelyne R; Shiferaw, Beletshachew; Kassenborg, Heidi D; Segler, Suzanne D; Marcus, Ruthanne; Daily, Pamala J; Hardnett, Felicia P; Slutsker, Laurence

    2004-04-15

    Among the population of the Foodborne Diseases Active Surveillance Network (FoodNet) surveillance areas ("FoodNet sites") in 1996, children under 12 months of age had the highest incidence of sporadic salmonellosis. We conducted a case-control study in 5 FoodNet sites to identify risk factors for sporadic infant salmonellosis. A case patient was a child under 12 months of age with a laboratory-confirmed, nontyphoidal serogroup B or D Salmonella infection. Twenty-two case patients were matched with 39 control subjects by age and either telephone exchange or vital record birth list. In a multivariate analysis, case patients were more likely to have a liquid diet containing no breast milk than a liquid diet containing only breast milk (matched odds ratio, 44.5; P=.04). Case-patients were more likely to reside in a household where a member had diarrhea (matched odds ratio, 13.2; P=.01). To decrease their infants' risk of salmonellosis, mothers should be encouraged to breast-feed their infants. Caretakers of infants should learn about salmonellosis, hand washing, and safe preparation of formula and solid food.

  17. Antiatherosclerotic effects of licorice extract supplementation on hypercholesterolemic patients: decreased CIMT, reduced plasma lipid levels, and decreased blood pressure.

    PubMed

    Fogelman, Yacov; Gaitini, Diana; Carmeli, Eli

    2016-01-01

    Ethanolic extract of licorice root has been shown to reduce low-density lipoprotein (LDL) oxidation in atherosclerotic mice and in both hypercholesterolemic and normal lipidemic humans. This study examined the effect of licorice-root extract on carotid intima-media thickness (CIMT) in individuals with hypercholesterolemia. Individuals with hypercholesterolemia (total cholesterol ≥6.18 mmol/L [240 mg/dL]) and without significant stenosis were randomly allocated to two groups: an experimental group that consumed 0.2 g/day of ethanolic extract of licorice root for 12 months, and a control group that received a placebo. Of 110 eligible participants, 94 (41-80 years old) completed the study. A significant CIMT decrease from 0.92±0.25 mm to 0.84±0.21 mm was observed in the experimental group compared with an increase from 0.85±0.17 mm to 0.88±0.19 mm in the control group. Mean plasma total cholesterol levels and LDL cholesterol decreased, at the range baseline to 1 year, from 284±32 mg/dl to 262±25 mg/dl and from 183±8.5 mg/dl to 174±9.1 mg/dl, respectively, for the experimental group (p<0.001) and from 291±35 to 289±31 mg/dl and from 177.6±10.7 to 179.3±9.6 (p=0.08), respectively, for the control group. Mean high-density lipoprotein (HDL) did not change significantly in either group. In the experimental group, systolic blood pressure decreased from 138±12 mmHg to 125±13 mmHg after 1 year (p=0.01) and increased from 136±15 mmHg to 137±13 mmHg in the control group. Diastolic blood pressure decreased from 92±9 mmHg to 84±10 mmHg (p=0.01) in the experimental group and increased from 89±11 mmHg to 90±8 mmHg in the control group. Following 1 year of licorice consumption, mean CIMT, total cholesterol, LDL levels, and blood pressure were decreased. This suggests that licorice may attenuate the development of atherosclerosis and of related cardiovascular diseases.

  18. Lymphaticovenous bypass decreases pathologic skin changes in upper extremity breast cancer-related lymphedema.

    PubMed

    Torrisi, Jeremy S; Joseph, Walter J; Ghanta, Swapna; Cuzzone, Daniel A; Albano, Nicholas J; Savetsky, Ira L; Gardenier, Jason C; Skoracki, Roman; Chang, David; Mehrara, Babak J

    2015-03-01

    Recent advances in microsurgery such as lymphaticovenous bypass (LVB) have been shown to decrease limb volumes and improve subjective symptoms in patients with lymphedema. However, to date, it remains unknown if these procedures can reverse the pathological tissue changes associated with lymphedema. Therefore, the purpose of this study was to analyze skin tissue changes in patients before and after LVB. Matched skin biopsy samples were collected from normal and lymphedematous limbs of 6 patients with unilateral breast cancer-related upper extremity lymphedema before and 6 months after LVB. Biopsy specimens were fixed and analyzed for inflammation, fibrosis, hyperkeratosis, and lymphangiogenesis. Six months following LVB, 83% of patients had symptomatic improvement in their lymphedema. Histological analysis at this time demonstrated a significant decrease in tissue CD4(+) cell inflammation in lymphedematous limb (but not normal limb) biopsies (p<0.01). These changes were associated with significantly decreased tissue fibrosis as demonstrated by decreased collagen type I deposition and TGF-β1 expression (all p<0.01). In addition, we found a significant decrease in epidermal thickness, decreased numbers of proliferating basal keratinocytes, and decreased number of LYVE-1(+) lymphatic vessels in lymphedematous limbs after LVB. We have shown, for the first time, that microsurgical LVB not only improves symptomatology of lymphedema but also helps to improve pathologic changes in the skin. These findings suggest that the some of the pathologic changes of lymphedema are reversible and may be related to lymphatic fluid stasis.

  19. Urtica dioica extract suppresses miR-21 and metastasis-related genes in breast cancer.

    PubMed

    Mansoori, Behzad; Mohammadi, Ali; Hashemzadeh, Shahriar; Shirjang, Solmaz; Baradaran, Ali; Asadi, Milad; Doustvandi, Mohammad Amin; Baradaran, Behzad

    2017-09-01

    Breast cancer has a high prevalence among women worldwide. Tumor invasion and metastasis still remains an open issue that causes most of the therapeutic failures and remains the prime cause of patient mortality. Hence, there is an unmet need to develop the most effective therapeutic approach with the lowest side effects and highest cytotoxicity that will effectively arrest or eradicate metastasis. An MTT assay and scratch test were used to assess the cytotoxicity and migration effects of Urtica dioica on the breast cancer cells. The QRT-PCR was used to study the expression levels of miR-21, MMP1, MMP9, MMP13, CXCR4, vimentin, and E-cadherin. The results of gene expression in tumoral groups confirmed the overexpression of miR-21, MMP1, MMP9, MMP13, vimentin, and CXCR4, and the lower expression of E-cadherin compared to control groups (P<0.05). Moreover, the results of the MTT assay show that Urtica dioica significantly inhibited breast cancer cell proliferation. Moreover, findings from the scratch assay exhibited the inhibitory effects of Urtica dioica on the migration of breast cancer cell lines. Urtica dioica extract could inhibit cancer cell migration by regulating miR-21, MMP1, MMP9, MMP13, vimentin, CXCR4, and E-Cadherin. Moreover, our findings demonstrated that the extract could decrease miR-21 expression, which substantially lessens the overexpressed MMP1, MMP9, MMP13, vimentin, and CXCR4 and increases E-cadherin in the tumoral group. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  20. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

    PubMed

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-02-28

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

  1. Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment

    PubMed Central

    Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

    2017-01-01

    Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer. PMID:28264501

  2. Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression.

    PubMed

    Borin, Thaiz Ferraz; Arbab, Ali Syed; Gelaleti, Gabriela Bottaro; Ferreira, Lívia Carvalho; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Iskander, A S M; Varma, Nadimpalli Ravi S; Shankar, Adarsh; Coimbra, Verena Benedick; Fabri, Vanessa Alves; de Oliveira, Juliana Garcia; Zuccari, Debora Aparecida Pires de Campos

    2016-01-01

    The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of 'hot' spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment.

  3. Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression

    PubMed Central

    Borin, Thaiz Ferraz; Arbab, Ali Syed; Gelaleti, Gabriela Bottaro; Ferreira, Lívia Carvalho; Moschetta, Marina Gobbe; Jardim-Perassi, Bruna Victorasso; Iskander, ASM; Varma, Nadimpalli Ravi S.; Shankar, Adarsh; Coimbra, Verena Benedick; Fabri, Vanessa Alves; de Oliveira, Juliana Garcia; de Campos Zuccari, Debora Aparecida Pires

    2016-01-01

    The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of ‘hot’ spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment. PMID:26292662

  4. Decreased ovarian hormones during a soya diet: implications for breast cancer prevention.

    PubMed

    Lu, L J; Anderson, K E; Grady, J J; Kohen, F; Nagamani, M

    2000-08-01

    Ovarian hormones are biomarkers for breast cancer risk. Soybean consumption may be responsible in part for lower levels of ovarian hormones and decreased rates of breast cancer in women in Asia compared with Western populations. Soybeans contain a significant amount of the isoflavones daidzein and genistein, which are weak estrogens. The purpose of this study was to determine whether soya feeding decreases circulating levels of ovarian hormones and gonadotropins. Ten healthy, regularly cycling women consumed a constant soya-containing diet on a metabolic unit, starting on day 2 of a menstrual cycle until day 2 of the next cycle. Blood and urine samples were obtained daily for one menstrual cycle before and during soy feeding. The diet was calculated to maintain constant body weight, included 400 kilocalories from a 36-ounce portion of soymilk, and provided 113-207 mg/day (154.0+/-8.4 mg/day, mean +/- SE) of total isoflavones. For the group, the soya diet provided more carbohydrate and less protein than the home diets. Daily consumption of the soya diet reduced circulating levels of 17beta-estradiol by 25% (P<0.01, Wilcoxon signed rank test, two-tailed) and of progesterone by 45% (P<0.0001) compared with levels during the home diet period but had no effect on luteinizing hormone or follicle-stimulating hormone. Mean menstrual cycle length did not change during the soya diet; a slight decrease in mean luteal cycle length was marginally statistically significant (P = 0.06). Urinary excretion of isoflavones was 33.8+/-5.3 mg/day (mean +/- SE) and when expressed as percentage of intake, varied substantially (21.9+/-3.3% of intake; range, 9.1-36.7%) among the subjects. Mean daily serum levels of daidzein and genistein (free and conjugated forms) 15 h after soymilk were 2.89+/-0.53 microg/ml and 0.85+/-0.22 microg/ml, respectively, indicating systemic bioavailability of these substances. Secondary analyses by multiple regression showed that decreases in follicular and

  5. [Effect of decreased GSH on sensitivity of breast cancer cells to ADM].

    PubMed

    Han, Xiao-qun; Li, Zhu-hua; Zhang, Jing-ge; Jiang, Yi-deng; Peng, Ke-jun; Wang, Li-zhen; Wang, Shu-ren

    2007-09-01

    Glutathione(GSH) maintains an optimum cellular redox potential. Elevated levels of GSH render some types of cancer cells resistant against anti-cancer drugs. The aim of this study was to determine the effect of a thiol-depleting agent, diethylmaleate (DEM), on the sensitivity of human breast cancer cells to ADM. The ADM-resistant human breast cancer MCF-7/ADM cell lines and ADM-sensitive MCF-7/S cell lines were treated by thiol-depleting agent DEM for 3 h respectively. The changes of sensitivity to ADM were then measured by MTT assay. The intracellular GSH contents were examined by fluorescent-spectrophotometry and the correlation between the changes of sensitivity to ADM and the intracellular GSH content was analyzed. Treatment of MCF-7/ADM and MCF-7/S cells by 0.1 micromol/L DEM for 3 h decreased 37.4% and 29.7% of the intracellular GSH content respectively (P < 0.01). ADM also decreased intracellular GSH content in a ADM-concentration-dependent manner. The combined use of DEM and ADM depleted the intracellular GSH content in both cells significantly more than the sum of single use of ADM and DEM alone. The sensitivity of both cells to ADM increased with the decline of intracellular GSH content. The depletion effect of DEM on the intracellular GSH could be enhanced by ADM and such depletion may be involved in the changes of the sensitivity of MCF/7 cells to ADM.

  6. Grape seed extract suppresses MDA-MB231 breast cancer cell migration and invasion.

    PubMed

    Dinicola, Simona; Pasqualato, Alessia; Cucina, Alessandra; Coluccia, Pierpaolo; Ferranti, Francesca; Canipari, Rita; Catizone, Angela; Proietti, Sara; D'Anselmi, Fabrizio; Ricci, Giulia; Palombo, Alessandro; Bizzarri, Mariano

    2014-01-01

    Breast cancer remains a leading cause of mortality among women. In metastasis, cascade migration of cancer cells and invasion of extracellular matrix (ECM) represent critical steps. Urokinase-type plasminogen activator (uPA), as well as metalloproteinases MMP-2 and MMP-9, strongly contribute to ECM remodelling, thus becoming associated with tumour migration and invasion. In addition, the high expression of cytoskeletal (CSK) proteins, as fascin, has been correlated with clinically aggressive metastatic tumours, and CSK proteins are thought to affect the migration of cancer cells. Consumption of fruits and vegetables, characterized by high procyanidin content, has been associated to a reduced mortality for breast cancer. Therefore, we investigated the biological effect of grape seed extract (GSE) on the highly metastatic MDA-MB231 breast cancer cell line, focusing on studying GSE ability in inhibiting two main metastatic processes, i.e., cell migration and invasion. After MDA-MB231 breast cancer cells stimulated with GSE migration and invasion were evaluated by means of trans-well assays and uPA as well as MMPs activity was detected by gelatin zymography. Fascin, β-catenin and nuclear factor-κB (NF-κB) expression were determined using western blot technique. β-Catenin localization was observed by confocal microscopy. We observed that high concentrations of GSE inhibited cell proliferation and apoptosis. Conversely, low GSE concentration decreased cell migration and invasion, likely by hampering β-catenin expression and localization, fascin and NF-κB expression, as well as by decreasing the activity of uPA, MMP-2 and MMP-9. These results make GSE a powerful candidate for developing preventive agents against cancer metastasis.

  7. Colocynth Extracts Prevent Epithelial to Mesenchymal Transition and Stemness of Breast Cancer Cells.

    PubMed

    Chowdhury, Kaushik; Sharma, Ankit; Kumar, Suresh; Gunjan, Gyanesh K; Nag, Alo; Mandal, Chandi C

    2017-01-01

    Modern treatment strategies provide better overall survival in cancer patients, primarily by controlling tumor growth. However, off-target and systemic toxicity, tumor recurrence, and resistance to therapy are still inadvertent hurdles in current treatment regimens. Similarly, metastasis is another deadly threat to patients suffering from cancer. This has created an urgent demand to come up with new drugs having anti-metastatic potential and minimum side effects. Thus, this study was aimed at exploring the anti-proliferative and anti-metastatic potential of colocynth medicinal plant. Results from MTT assay, morphological visualization of cells and scratch assay indicated a role of ethanol and acetone extracts of fruit pulp of the colocynth plant in inhibiting cell viability, enhancing cell cytotoxicity and preventing cell migration in various cancer cell types, including breast cancer cell lines MCF-7 and MDA-MB-231, and cervical cancer cell line SiHa, subsequently having a low cytotoxic effect on mononuclear PBMC and macrophage J774A cells. Our study in metastatic MDA-MB-231 cells showed that both ethanol and acetone pulp extracts decreased transcript levels of the anti-apoptotic genes BCL2 and BCLXL, and a reverse effect was observed for the pro-apoptotic genes BAX and caspase 3. Additionally, enhanced caspase 3 activity and downregulated BCL2 protein were seen, indicating a role of these extracts in inducing apoptotic activity. Moreover, MDA-MB-231 cells treated with both these extracts demonstrated up-regulation of the epithelial gene keratin 19 and down-regulation of the mesenchymal genes, vimentin, N-cadherin, Zeb1 and Zeb2 compared to control, suggesting a suppressive impact of these extracts in epithelial to mesenchymal transition (EMT). In addition, these extracts inhibited colony and sphere formation with simultaneous reduction in the transcript level of the stemness associated genes, BMI-1 and CD44. It was also found that both the plant extracts

  8. Anticarcinogenic Activity of Strawberry, Blueberry, and Raspberry Extracts to Breast and Cervical Cancer Cells.

    PubMed

    Wedge, David E.; Meepagala, Kumudini M.; Magee, James B.; Smith, S. Hope; Huang, George; Larcom, Lyndon L.

    2001-01-01

    Freeze-dried fruits of two strawberry cultivars, Sweet Charlie and Carlsbad, and two blueberry cultivars, Tifblue and Premier were sequentially extracted with hexane, 50% hexane/ethyl acetate, ethyl acetate, ethanol, and 70% acetone/water at ambient temperature. Each extract was tested separately for in vitro anticancer activity on cervical and breast cancer cell lines. Ethanol extracts from all four fruits strongly inhibited CaSki and SiHa cervical cancer cell lines and MCF-7 and T47-D breast cancer cell lines. An unfractionated aqueous extract of raspberry and the ethanol extract of Premier blueberry significantly inhibited mutagenesis by both direct-acting and metabolically activated carcinogens.

  9. Increased Flap Weight and Decreased Perforator Number Predict Fat Necrosis in DIEP Breast Reconstruction.

    PubMed

    Mulvey, Carolyn L; Cooney, Carisa M; Daily, Francis F; Colantuoni, Elizabeth; Ogbuago, Onyebuchi U; Cooney, Damon S; Rad, Ariel N; Manahan, Michele A; Rosson, Gedge D; Sacks, Justin M

    2013-05-01

    Compromised perfusion in autologous breast reconstruction results in fat necrosis and flap loss. Increased flap weight with fewer perforator vessels may exacerbate imbalances in flap perfusion. We studied deep inferior epigastric perforator (DIEP) and muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps to assess this concept. Data from patients who underwent reconstruction with DIEP and/or MS-TRAM flaps between January 1, 2010 and December 31, 2011 (n = 123) were retrospectively reviewed. Patient demographics, comorbidities, intraoperative parameters, and postoperative outcomes were collected, including flap fat necrosis and donor/recipient site complications. Logistic regression analysis was used to examine effects of flap weight and perforator number on breast flap fat necrosis. One hundred twenty-three patients who underwent 179 total flap reconstructions (166 DIEP, 13 MS-TRAM) were included. Mean flap weight was 658 ± 289 g; 132 (73.7%) were single perforator flaps. Thirteen flaps (7.5%) developed fat necrosis. African American patients had increased odds of fat necrosis (odds ratio, 11.58; P < 0.001). Odds of developing fat necrosis significantly increased with flap weight (odds ratio, 1.5 per 100 g increase; P < 0.001). In single perforator flaps weighing more than 1000 g, six (42.9%) developed fat necrosis, compared to 14.3% of large multiple perforator flaps. Flaps with increasing weight have increased risk of fat necrosis. These data suggest that inclusion of more than 1 perforator may decrease odds of fat necrosis in large flaps. Perforator flap breast reconstruction can be performed safely; however, considerations concerning race, body mass index, staging with tissue expanders, perforator number, and flap weight may optimize outcomes.

  10. Increased Flap Weight and Decreased Perforator Number Predict Fat Necrosis in DIEP Breast Reconstruction

    PubMed Central

    Mulvey, Carolyn L.; Cooney, Carisa M.; Daily, Francis F.; Colantuoni, Elizabeth; Ogbuago, Onyebuchi U.; Cooney, Damon S.; Rad, Ariel N.; Manahan, Michele A.; Rosson, Gedge D.

    2013-01-01

    Background: Compromised perfusion in autologous breast reconstruction results in fat necrosis and flap loss. Increased flap weight with fewer perforator vessels may exacerbate imbalances in flap perfusion. We studied deep inferior epigastric perforator (DIEP) and muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps to assess this concept. Methods: Data from patients who underwent reconstruction with DIEP and/or MS-TRAM flaps between January 1, 2010 and December 31, 2011 (n = 123) were retrospectively reviewed. Patient demographics, comorbidities, intraoperative parameters, and postoperative outcomes were collected, including flap fat necrosis and donor/recipient site complications. Logistic regression analysis was used to examine effects of flap weight and perforator number on breast flap fat necrosis. Results: One hundred twenty-three patients who underwent 179 total flap reconstructions (166 DIEP, 13 MS-TRAM) were included. Mean flap weight was 658 ± 289 g; 132 (73.7%) were single perforator flaps. Thirteen flaps (7.5%) developed fat necrosis. African American patients had increased odds of fat necrosis (odds ratio, 11.58; P < 0.001). Odds of developing fat necrosis significantly increased with flap weight (odds ratio, 1.5 per 100 g increase; P < 0.001). In single perforator flaps weighing more than 1000 g, six (42.9%) developed fat necrosis, compared to 14.3% of large multiple perforator flaps. Conclusions: Flaps with increasing weight have increased risk of fat necrosis. These data suggest that inclusion of more than 1 perforator may decrease odds of fat necrosis in large flaps. Perforator flap breast reconstruction can be performed safely; however, considerations concerning race, body mass index, staging with tissue expanders, perforator number, and flap weight may optimize outcomes. PMID:25289212

  11. Apocynin Derivatives Interrupt Intracellular Signaling Resulting in Decreased Migration in Breast Cancer Cells

    PubMed Central

    Klees, Robert F.; De Marco, Paul C.; Salasznyk, Roman M.; Ahuja, Disha; Hogg, Michael; Antoniotti, Sylvain; Kamath, Lakshmi; Dordick, Jonathan S.; Plopper, George E.

    2006-01-01

    Cancer cells are defined by their ability to divide uncontrollably and metastasize to secondary sites in the body. Consequently, tumor cell migration represents a promising target for anticancer drug development. Using our high-throughput cell migration assay, we have screened several classes of compounds for noncytotoxic tumor cell migration inhibiting activity. One such compound, apocynin (4-acetovanillone), is oxidized by peroxidases to yield a variety of oligophenolic and quinone-type compounds that are recognized inhibitors of NADPH oxidase and may be inhibitors of the small G protein Rac1 that controls cell migration. We report here that while apocynin itself is not effective, apocynin derivatives inhibit migration of the breast cancer cell line MDA-MB-435 at subtoxic concentrations; the migration of nonmalignant MCF10A breast cells is unaffected. These compounds also cause a significant rearrangement of the actin cytoskeleton, cell rounding, and decreased levels of active Rac1 and its related G protein Cdc42. These results may suggest a promising new route to the development of novel anticancer therapeutics. PMID:16883056

  12. Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells.

    PubMed

    González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; Sánchez-Martínez, Ruth; Vargas, Teodoro; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

    2014-06-01

    Breast cancer is the leading cause of cancer-related mortality among females worldwide, and therefore the development of new therapeutic approaches is still needed. Rosemary (Rosmarinus officinalis L.) extract possesses antitumor properties against tumor cells from several organs, including breast. However, in order to apply it as a complementary therapeutic agent in breast cancer, more information is needed regarding the sensitivity of the different breast tumor subtypes and its effect in combination with the currently used chemotherapy. Here, we analyzed the antitumor activities of a supercritical fluid rosemary extract (SFRE) in different breast cancer cells, and used a genomic approach to explore its effect on the modulation of ER-α and HER2 signaling pathways, the most important mitogen pathways related to breast cancer progression. We found that SFRE exerts antitumor activity against breast cancer cells from different tumor subtypes and the downregulation of ER-α and HER2 receptors by SFRE might be involved in its antitumor effect against estrogen-dependent (ER+) and HER2 overexpressing (HER2+) breast cancer subtypes. Moreover, SFRE significantly enhanced the effect of breast cancer chemotherapy (tamoxifen, trastuzumab, and paclitaxel). Overall, our results support the potential utility of SFRE as a complementary approach in breast cancer therapy.

  13. 17β-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level

    SciTech Connect

    Zhao, Ziyi; Chen, Changjin; Liu, Yu; Wu, Chuanfang

    2014-03-07

    Highlights: • E2 affects not only estrogen-receptor α positive breast cells but also negative ones. • 100 nM E2 treatment affects breast cells proliferation, migration. • 100 nM E2 treatment functions in an estrogen-receptor α-independent way. • E2 treatment decreases MALAT-1 RNA level by post-transcriptional regulation. - Abstract: Breast cancer cells, which express estrogen receptor α (ERα), respond to estrogen in a concentration dependent fashion, resulting in proliferation or apoptosis. But breast cancer cells without ERα show no effect on low concentration of estrogen treatment. Proliferation, migration and invasion of MCF10a, MCF7 and MB231 cells treated with low (1 nM) or high (100 nM) dose of 17β-Estradiol (E2) was performed. We identified the effects of E2 on these breast cell lines, and looked for the difference in the presence and absence of ERα. Specifically, we looked for the changes of long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT-1), which is found extensively and highly expressed in several kinds of tumor cells, including breast carcinoma. It was observed that proliferation, migration and invasion of breast cells were greatly affected by high concentration E2 treatment and were not affected by low concentration E2 treatment in an ERα independent way. We found that the high concentration E2 treatment largely decreased MALAT-1 RNA level. Interestingly, MALAT-1 decreasing by knocking down showed similar effects on proliferation, migration and invasion. E2 treatment affects breast tumor or non-tumor cells proliferation, migration and invasion in an ERα -independent, but a dose-dependent way by decreasing the MALAT-1 RNA level.

  14. Phenylboronic acid selectively inhibits human prostate and breast cancer cell migration and decreases viability.

    PubMed

    Bradke, Tiffany M; Hall, Casey; Carper, Stephen W; Plopper, George E

    2008-01-01

    We compared the in vitro effect of boric acid (BA) versus phenylboronic acid (PBA) on the migration of prostate and breast cancer cell lines and non-tumorigenic cells from the same tissues. Treatment at 24 hours with BA (< or =500 microM) did not inhibit chemotaxis on fibronectin in any cell line. However, treatment over the same time course with concentrations of PBA as low as 1 muM significantly inhibited cancer cell migration without effecting non-tumorigenic cell lines. The compounds did not affect cell adhesion or viability at 24 hours but did alter morphology; both decreased cancer cell viability at eight days. These results suggest that PBA is more potent than BA in targeting the metastatic and proliferative properties of cancer cells.

  15. Toad skin extract cinobufatini inhibits migration of human breast carcinoma MDA-MB-231 cells into a model stromal tissue.

    PubMed

    Nakata, Munehiro; Mori, Shuya; Kamoshida, Yo; Kawaguchi, Shota; Fujita-Yamaguchi, Yoko; Gao, Bo; Tang, Wei

    2015-08-01

    Toad skin extract cinobufatini study has been focused on anticancer activity, especially apoptosis-inducing activity by bufosteroids. The present study examined effect of the toad skin extract on cancer cell migration into model stromal tissues. Human breast carcinoma cell line MDA-MB-231 was incubated in the presence or absence of toad skin extract on a surface of reconstituted type I collagen gel as a model stromal tissue allowing the cells to migrate into the gel. Frozen sections were microscopically observed after azan staining. Data showed a decrease of cell number in a microscopic field and shortening of cell migration into the model stromal tissue in a dose dependent manner. This suggests that toad skin extract may possess migration-preventing activity in addition to cell toxicity such as apoptosis-inducing activity. The multifaceted effects including apoptosis-inducing and cancer cell migration-preventing activities would improve usefulness of toad skin extract cinobufatini as an anticancer medicine.

  16. An aqueous extract of guaraná (Paullinia cupana) decreases platelet thromboxane synthesis.

    PubMed

    Bydlowski, S P; D'Amico, E A; Chamone, D A

    1991-01-01

    The effects of an aqueous extract of guaraná (Paullinia cupana) on rabbit platelet aggregation and thromboxane synthesis were examined. The guaraná extract (100 mg/ml) and fractions separated by TLC (origin and xanthines) decreased platelet aggregation (37, 27 and 31% of control values, respectively) and platelet thromboxane formation from [14C]-arachidonic acid (78, 70 and 50% of control values, respectively). The decreased thromboxane synthesis could be responsible, at least in part, for the antiaggregatory action of guaraná.

  17. Declining incidence of breast cancer after decreased use of hormone-replacement therapy: magnitude and time lags in different countries.

    PubMed

    Zbuk, Kevin; Anand, Sonia S

    2012-01-01

    Throughout the latter half of the 20th century, hormone-replacement therapy (HRT) use steadily increased in the Western world. In 2002, the early termination of the Women's Health Initiative trial due to an excess of adverse events attributable to HRT, led to a precipitous decline in its use. Breast cancer incidence began to decline soon thereafter in the USA and several other countries. However, the magnitude of the decline in breast cancer incidence, and its timing with respect to HRT cessation, shows considerable variability between nations. The impact of HRT cessation appears most significant and immediate in countries with the largest absolute decline in HRT use. In countries in which peak prevalence of HRT use was high, several studies have convincingly excluded decreasing rates of mammographic screening as an explanation for the decline in breast cancer incidence. Conversely, in some countries, no decline in breast cancer incidence is apparent that can be readily attributed to declining trends in HRT use. In such cases, declines in breast cancer incidence may be related instead to saturation or decreased utilisation of mammographic screening programmes. In other cases, it is difficult to disentangle the respective influence of trends in HRT use, and the influence of changes relating to mammographic screening. However, irrespective of time lags and varying magnitudes of effect, the data convincingly support a direct association between decreasing HRT use and declining breast cancer incidence.

  18. Effect of Ginger Extract and Citric Acid on the Tenderness of Duck Breast Muscles

    PubMed Central

    2015-01-01

    The objective of this study was to examine the effect of ginger extract (GE) combined with citric acid on the tenderness of duck breast muscles. Total six marinades were prepared with the combination of citric acid (0 and 0.3 M citric acid) and GE (0, 15, and 30%). Each marinade was sprayed on the surface of duck breasts (15 mL/100 g), and the samples were marinated for 72 h at 4℃. The pH and proteolytic activity of marinades were determined. After 72 h of marination, Warner Bratzler shear force (WBSF), myofibrillar fragmentation index (MFI), pH, cooking loss, moisture content, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and protein solubility were evaluated. There was no significant (p>0.05) difference in moisture content or cooking loss among all samples. However, GE marination resulted in a significant (p<0.05) decrease in WBSF but a significant (p<0.05) increase in pH and MFI. In addition, total protein and myofibrillar protein solubility of GE-marinated duck breast muscles in both WOC (without citric acid) and WC (with citric acid) conditions were significantly (p<0.05) increased compared to non-GE-marinated duck breast muscles. SDS-PAGE showed an increase of protein degradation (MHC and actin) in WC condition compared to WOC condition. There was a marked actin reduction in GE-treated samples in WC. The tenderization effect of GE combined with citric acid may be attributed to various mechanisms such as increased MFI and myofibrillar protein solubility. PMID:26877631

  19. The Urtica dioica extract enhances sensitivity of paclitaxel drug to MDA-MB-468 breast cancer cells.

    PubMed

    Mohammadi, Ali; Mansoori, Behzad; Aghapour, Mahyar; Shirjang, Solmaz; Nami, Sanam; Baradaran, Behzad

    2016-10-01

    Due to the chemo resistant nature of cancer cells and adverse effects of current therapies, researchers are looking for the most efficient therapeutic approach which has the lowest side effects and the highest toxicity on cancer cells. The aim of the present study was to investigate the synergic effect of Urtica dioica extract in combination with paclitaxel on cell death and invasion of human breast cancer MDA-MB-468 cell line. To determine the cytotoxic effects of Urtica dioica extract with paclitaxel, MTT assay was performed. The scratch test was exploited to assess the effects of Urtica dioica, Paclitaxel alone and combination on migration of cancer cells. The expression levels of snail-1, ZEB1, ZEB2, twist, Cdc2, cyclin B1 and Wee1 genes were quantified using qRT-PCR and western blot performed for snail-1expression. The effects of plant extract, Paclitaxel alone and combination on different phases of cell cycle was analyzed using flow cytometry. Results of MTT assay showed that Urtica dioica significantly destroyed cancer cells. Interestingly, Concurrent use of Urtica dioica extract with paclitaxel resulted in decreased IC50 dose of paclitaxel. Moreover, findings of scratch assay exhibited the inhibitory effects of Urtica dioica, Paclitaxel alone and combination on migration of MDA-MB-468 cell line. Our findings also demonstrated that the extract substantially decreased the Snail-1 and related gene expression. Ultimately, Cell cycle arrest occurred at G2/M phase post-treatment by deregulating Cdc2 and wee1. Our results demonstrated that the dichloromethane extract of Urtica dioica inhibit cell growth and migration. Also, Urtica dioica extract substantially increased sensitivity of breast cancer cells to paclitaxel. Therefore, it can be used as a potential candidate for treatment of breast cancer with paclitaxel. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Inhibition of the Rho GTPase, Rac1, decreases estrogen receptor levels and is a novel therapeutic strategy in breast cancer.

    PubMed

    Rosenblatt, Adena E; Garcia, Maria Ines; Lyons, Leah; Xie, Yingqiu; Maiorino, Carol; Désiré, Laurent; Slingerland, Joyce; Burnstein, Kerry L

    2011-04-01

    Rac1, a Rho GTPase, modulates diverse cellular processes and is hyperactive in some cancers. Estrogen receptor-alpha (ERα) in concert with intracellular signaling pathways regulates genes associated with cell proliferation, tumor development, and breast cancer cell survival. Therefore, we examined the possibility of Rac1 and ERα crosstalk in breast cancer cells. We found that Rac1 enhanced ERα transcriptional activity in breast cancer cells. Vav3, a Rho guanine nucleotide exchange factor that activates Rac1, was an upstream mediator, and P21/Cdc42/Rac1 activating kinase-1 (Pak-1) was a downstream effector of Rac1 enhancement of ERα activity. These results suggest that Rac1 may prove to be a therapeutic target. To test this hypothesis, we used a small molecule Rac inhibitor, EHT 1864, and found that EHT 1864 inhibited ERα transcriptional activity. Furthermore, EHT 1864 inhibited estrogen-induced cell proliferation in breast cancer cells and decreased tamoxifen-resistant breast cancer cell growth. EHT 1864 decreased activity of the promoter of the ERα gene resulting in down-regulation of ERα mRNA and protein levels. Therefore, ERα down-regulation by EHT 1864 is the likely mechanism of EHT 1864-mediated inhibition of ERα activity and estrogen-stimulated breast cancer cell proliferation. Since ERα plays a critical role in the pathogenesis of breast cancer and the Rac inhibitor EHT 1864 down-regulates ERα expression and breast cancer cell proliferation, further investigation of the therapeutic potential of Rac1 targeting in the treatment of breast cancer is warranted.

  1. Feature extraction using convolutional neural network for classifying breast density in mammographic images

    NASA Astrophysics Data System (ADS)

    Thomaz, Ricardo L.; Carneiro, Pedro C.; Patrocinio, Ana C.

    2017-03-01

    Breast cancer is the leading cause of death for women in most countries. The high levels of mortality relate mostly to late diagnosis and to the direct proportionally relationship between breast density and breast cancer development. Therefore, the correct assessment of breast density is important to provide better screening for higher risk patients. However, in modern digital mammography the discrimination among breast densities is highly complex due to increased contrast and visual information for all densities. Thus, a computational system for classifying breast density might be a useful tool for aiding medical staff. Several machine-learning algorithms are already capable of classifying small number of classes with good accuracy. However, machinelearning algorithms main constraint relates to the set of features extracted and used for classification. Although well-known feature extraction techniques might provide a good set of features, it is a complex task to select an initial set during design of a classifier. Thus, we propose feature extraction using a Convolutional Neural Network (CNN) for classifying breast density by a usual machine-learning classifier. We used 307 mammographic images downsampled to 260x200 pixels to train a CNN and extract features from a deep layer. After training, the activation of 8 neurons from a deep fully connected layer are extracted and used as features. Then, these features are feedforward to a single hidden layer neural network that is cross-validated using 10-folds to classify among four classes of breast density. The global accuracy of this method is 98.4%, presenting only 1.6% of misclassification. However, the small set of samples and memory constraints required the reuse of data in both CNN and MLP-NN, therefore overfitting might have influenced the results even though we cross-validated the network. Thus, although we presented a promising method for extracting features and classifying breast density, a greater database is

  2. Ocimum basilicum ethanolic extract decreases cholesterol synthesis and lipid accumulation in human macrophages.

    PubMed

    Bravo, Elena; Amrani, Souliman; Aziz, Mohammed; Harnafi, Hicham; Napolitano, Mariarosaria

    2008-12-01

    Macrophage lipid accumulation induced by low density lipoproteins (LDL) plays a pivotal role in atherosclerotic plaque development. Previous work showed that Ocimum basilicum extract, used as hypocholesterolemic agent by traditional medicine in Morocco, has hypolipidemic activity in rat acute hyperlipimidemia. This study investigated the effects of ethanolic extract of O. basilicum on lipid accumulation in human macrophages. As modification of LDL increase atherogenicity of the particles we evaluated the effects of the extract on LDL oxidation. The extract caused a dose-related increase of LDL-resistance to Cu(2+)-induced oxidation. Furthermore, at the dose of 60 microg/ml, significantly decreases the accumulation of macrophage lipid droplets induced by modified LDL evaluated as by red-oil staining. Cholesterol esterification and triacylglycerol synthesis in the cells were not affected. Macrophage treatment with 60 microg/ml, but not 20 microg/ml, of the extract reduced newly synthesized unesterified cholesterol by about 60% and decreased scavenger receptors activity by about 20-30%, evaluated by the internalization of cholesterol carried by [(3)H]CE-aggregated-LDL. The results suggest that O. basilicum ethanolic extract has the capability to reduce foam cell formation through the reduction of cholesterol synthesis and the modulation of the activity of surface scavenger receptors.

  3. Oxidative stress-mediated apoptosis induced by ethanolic mango seed extract in cultured estrogen receptor positive breast cancer MCF-7 cells.

    PubMed

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Rasedee, Abdullah; Mirghani, Mohamed Elwathig Saeed

    2015-02-05

    Breast cancer has become a global health issue requiring huge expenditures for care and treatment of patients. There is a need to discover newer cost-effective alternatives for current therapeutic regimes. Mango kernel is a waste product with potential as a source of anti-cancer phytochemicals, especially since it is non-toxic towards normal breast cell lines at concentrations for which it induces cell death in breast cancer cells. In this study, the anti-cancer effect of mango kernel extract was determined on estrogen receptor-positive human breast carcinoma (MCF-7) cells. The MCF-7 cells were cultured and treated with 5, 10 and 50 μg/mL of mango kernel extract for 12 and 24 h. In response to treatment, there were time- and dose-dependent increases in oxidative stress markers and pro-apoptotic factors; Bcl-2-like protein 4 (BAX), p53, cytochrome c and caspases (7, 8 and 9) in the MCF-7 cells treated with the extract. At the same time, there were decreases in pro-survival markers (Bcl-2 and glutathione) as the result of the treatments. The changes induced in the MCF-7 cells by mango kernel extract treatment suggest that the extract can induce cancer cell apoptosis, likely via the activation of oxidative stress. These findings need to be evaluated further to determine whether mango kernel extract can be developed as an anti-breast cancer agent.

  4. Evaluation of aqueous extracts of Taraxacum officinale on growth and invasion of breast and prostate cancer cells.

    PubMed

    Sigstedt, Sophia C; Hooten, Carla J; Callewaert, Manika C; Jenkins, Aaron R; Romero, Anntherese E; Pullin, Michael J; Kornienko, Alexander; Lowrey, Timothy K; Slambrouck, Severine Van; Steelant, Wim F A

    2008-05-01

    Ethnotraditional use of plant-derived natural products plays a significant role in the discovery and development of potential medicinal agents. Plants of the genus Taraxacum, commonly known as dandelions, have a history of use in Chinese, Arabian and Native American traditional medicine, to treat a variety of diseases including cancer. To date, however, very few studies have been reported on the anti-carcinogenic activity of Taraxacum officinale (TO). In the present study, three aqueous extracts were prepared from the mature leaves, flowers and roots, and investigated on tumor progression related processes such as proliferation and invasion. Our results show that the crude extract of dandelion leaf (DLE) decreased the growth of MCF-7/AZ breast cancer cells in an ERK-dependent manner, whereas the aqueous extracts of dandelion flower (DFE) and root (DRE) had no effect on the growth of either cell line. Furthermore, DRE was found to block invasion of MCF-7/AZ breast cancer cells while DLE blocked the invasion of LNCaP prostate cancer cells, into collagen type I. Inhibition of invasion was further evidenced by decreased phosphorylation levels of FAK and src as well as reduced activities of matrix metalloproteinases, MMP-2 and MMP-9. This study provides new scientific data on TO and suggests that TO extracts or individual components present in the extracts may be of value as novel anti-cancer agents.

  5. Behavioral activation and problem-solving therapy for depressed breast cancer patients: preliminary support for decreased suicidal ideation.

    PubMed

    Hopko, D R; Funderburk, J S; Shorey, R C; McIndoo, C C; Ryba, M M; File, A A; Benson, K; Vitulano, M

    2013-11-01

    Major depressive disorder (MDD) is the most common psychiatric disorder in breast cancer patients. The prevalence of suicidal ideation in breast cancer patients is considerable, and relative to the general population, the prevalence of completed suicide is elevated, particularly in cancer patients with MDD. A major component of suicide prevention is effective treatment of MDD. Although some research has explored the utility of psychotherapy with breast cancer patients, only three trials have explored the benefits of behavior therapy in patients with well-diagnosed MDD and there has been no systematic investigation of the potential benefits of psychotherapy toward reducing suicidal ideation in breast cancer patients. As a follow-up to a recently completed randomized trial, this study examined the efficacy of 8 weeks of behavioral activation treatment for depression (BATD) and problem-solving therapy (PST) in reducing depression and suicidal ideation, as well as increasing hopefulness in breast cancer patients with MDD (n = 80). Across both treatments, GEE analyses revealed decreased depression and suicidal ideation and increased hopefulness at posttreatment, results that were maintained at 12-month follow-up. Moreover, follow-up patient contact at approximately 2 years posttreatment yielded no indication of completed suicide. Although these data are preliminary, BATD and PST may represent practical approaches to decrease suicidal ideation in depressed breast cancer patients.

  6. Macleaya cordata Extract Decreased Diarrhea Score and Enhanced Intestinal Barrier Function in Growing Piglets

    PubMed Central

    Fang, Jun; Martínez, Yordan; Bin, Peng; Duraipandiyan, Veeramuthu; Yin, Yulong

    2016-01-01

    Macleaya cordata extract is of great scientific and practical interest to researchers, due to its antimicrobial and anti-inflammatory responses within experimental animals. This study was designed to determine the diarrhea score and innate immunity of growing piglets after they had received Macleaya cordata extract supplements. A total of 240 growing pigs were randomly assigned to one of three dietary treatments, with 8 replicates per treatment and 10 piglets per replicate. All pigs received a basal diet containing similar amounts of nutrients. The three treatments were a control (no additive), an antibiotic (200 mg/kg colistin), and the Macleaya cordata extract supplement group (40 mg/kg Macleaya cordata extract). The diarrhea score was calculated after D 28. The jejunal samples were obtained from five piglets selected randomly from each treatment on D 28. In comparison with the control group, the dietary Macleaya cordata extract and colistin group demonstrated a substantially decreased diarrhea score. The introduction of Macleaya cordata extract supplements to the diet significantly increased volumes of ZO-1 and claudin-1, particularly in comparison with the pigs in the control group (P < 0.05). The findings indicate that Macleaya cordata extract does enhance intestinal barrier function in growing piglets and that it could be used as a viable substitute for antibiotics. PMID:27525260

  7. Kefir extracts suppress in vitro proliferation of estrogen-dependent human breast cancer cells but not normal mammary epithelial cells.

    PubMed

    Chen, Chujian; Chan, Hing Man; Kubow, Stan

    2007-09-01

    Anti-tumorigenic effects have been demonstrated in animal studies from the intake of kefir, a traditional fermented milk product believed to originate from the Caucasian mountains of Russia. In the present study, the antiproliferative effects of extracts of kefir, yogurt, and pasteurized cow's milk on human mammary cancer cells (MCF-7) and normal human mammary epithelial cells (HMECs) was investigated at doses of 0.31%, 0.63%, 1.25%, 2.5%, 5%, and 10% (vol/vol). After 6 days of culture, extracts of kefir-fermented milk depressed MCF-7 cell growth in a dose-dependent manner, showing 29% inhibition of proliferation at a concentration as low as 0.63%, whereas yogurt extracts began to show dose-dependent antiproliferative effects only at the 2.5% dose. Moreover, at the 2.5% dose, kefir extracts decreased the MCF-7 cell numbers by 56%, while yogurt extracts decreased MCF-7 cell proliferation by only 14%. No antiproliferative effects of kefir extracts were observed in the HMECs, while the yogurt extracts exerted antiproliferative effects on HMECs at the 5% and 10% doses. Unfermented milk extracts stimulated proliferation of MCF-7 cells and HMECs at concentrations above 0.31%. Peptide content and capillary electrophoresis analyses showed that kefir-mediated milk fermentation led to an increase in peptide concentrations and a change in peptide profiles relative to milk or yogurt. The present findings suggest that kefir extracts contain constituents that specifically inhibit the growth of human breast cancer cells, which might eventually be useful in the prevention or treatment of breast cancer.

  8. CDH1 promoter methylation correlates with decreased gene expression and poor prognosis in patients with breast cancer.

    PubMed

    Liu, Jian; Sun, Xin; Qin, Sida; Wang, Huangzhen; DU, Ning; Li, Yanbo; Pang, Yamei; Wang, Cuicui; Xu, Chongwen; Ren, Hong

    2016-04-01

    The E-cadherin gene (CDH1) is associated with poor prognosis and metastasis in patients with breast cancer, and methylation of its promoter is correlated with decreased gene expression. However, there is currently no direct evidence that CDH1 promoter methylation indicates poor prognosis in patients with breast cancer. In the present study, methylation-specific polymerase chain reaction (PCR) was applied to detect the methylation status of the CDH1 promoter in 137 primary breast cancer, 85 matched normal breast tissue and 13 lung metastasis specimens. Reverse transcription-quantitative PCR was used to assess the relative expression levels of CDH1 mRNA, and correlation analysis between CDH1 methylation status, and gene expression, clinicopathological characteristics and patient survival was performed. Methylation of CDH1 was identified in 40.9% (56/137) of primary breast cancer specimens, 61.5% (8/13) of lung metastasis specimens and none of the matched normal breast specimens. The downregulation of CDH1 mRNA and E-cadherin protein expression were identified to be significantly correlated with CDH1 methylation (P<0.05). In addition, CDH1 methylation was significantly associated with lymph node metastasis and estrogen receptor status of patients (P<0.05). In univariate analyses, patients with CDH1 methylation exhibited poor overall survival (OS) and disease-free survival (DFS; P<0.05). Furthermore, multivariate analyses revealed that CDH1 methylation was an independent prognostic factor predicting poor OS (HR, 1.737; 95% CI, 0.957-3.766; P=0.041) and DFS (HR, 2.018; 95% CI, 2.057-3.845; P=0.033) in patients with breast cancer. Therefore, the present study suggests that CDH1 promoter methylation may be correlated with breast carcinogenesis and indicates poor prognosis in patients with breast cancer.

  9. CONJUGATED LINOLEIC ACIDS (CLA) DECREASE THE BREAST CANCER RISK IN DMBA-TREATED RATS.

    PubMed

    Białek, Agnieszka; Tokarz, Andrzej; Zagrodzki, Paweł

    2016-01-01

    The aim of this study was to investigate how supplementation of diet of female Sprague-Dawley rats with different doses of conjugated linoleic acids and for a varied period of time influences breast cancer risk, fatty acids profile and lipids peroxidation in chemically induced mammary tumors. Animals were divided into nine groups with different modifications of diet (vegetable oil, 1.0 or 2.0% of CLA) and period of supplementation, which lasted after (A), before (B) and before and after (BA) carcinogenic agent--7,12-dimethylbenz[a]anthracene administration at 50th day of life. Mammary adenocarcinomas occurred in all groups, but CLA supplementation decreased the cancer morbidity. Two percent CLA seems to be excessive because of the coexisting cachexia. Two CLA isomers (9-cis, 11-trans and 10-trans, 12-cis) were detected in tumors but content of rumenic acid was higher. Dietary supplementation significantly influenced some unsaturated fatty acids content (C18:2 n-6 trans, C20:1, C20:5 n-3, C22:2), but the anti- or prooxidant properties of CLA were not confirmed. CLA can inhibit chemically induced mammary tumors development in female rats, but their cytotoxic action seems not to be connected with lipids peroxidation. CLA isomers differ with their incorporation into cancerous tissues and they influence the content of some other fatty acids.

  10. Decreased NK-cell tumour immunosurveillance consequent to JAK inhibition enhances metastasis in breast cancer models

    PubMed Central

    Bottos, Alessia; Gotthardt, Dagmar; Gill, Jason W.; Gattelli, Albana; Frei, Anna; Tzankov, Alexandar; Sexl, Veronika; Wodnar-Filipowicz, Aleksandra; Hynes, Nancy E.

    2016-01-01

    The JAK/STAT pathway is an attractive target for breast cancer therapy due to its frequent activation, and clinical trials evaluating JAK inhibitors (JAKi) in advanced breast cancer are ongoing. Using patient biopsies and preclinical models of breast cancer, we demonstrate that the JAK/STAT pathway is active in metastasis. Unexpectedly, blocking the pathway with JAKi enhances the metastatic burden in experimental and orthotopic models of breast cancer metastasis. We demonstrate that this prometastatic effect is due to the immunosuppressive activity of JAKi with ensuing impairment of NK-cell-mediated anti-tumour immunity. Furthermore, we show that immunostimulation with IL-15 overcomes the enhancing effect of JAKi on metastasis formation. Our findings highlight the importance of evaluating the effect of targeted therapy on the tumour environment. The impact of JAKi on NK cells and the potential value of immunostimulators to overcome the weakened tumour immunosurveillance, are worthwhile considering in the clinical setting of breast cancer. PMID:27406745

  11. Progression of breast tumors is accompanied by a decrease in expression of the Rho guanine exchange factor Tiam1.

    PubMed

    Stebel, A; Brachetti, C; Kunkel, M; Schmidt, M; Fritz, G

    2009-01-01

    In this study, we investigated the expression level of Ras-homologous (Rho) GTPases and the Rho guanine exchange factor (GEF) T-cell lymphoma invasion and metastasis 1 (Tiam1) in breast tumor specimens (n=106) by immunohistochemistry. Rho and Rho-GEF expression scores were compared to clinically established diagnostic and prognostic parameters. We found that RhoA and RhoB scores slightly increased with tumor grade, whereas the Rac1 score remained unaffected. The most significant effects were observed for the Rac1-specific GEF Tiam1. Tiam1 expression scores significantly decreased with the increase in tumor grade, tumor spreading and proliferation. Furthermore, Tiam1 expression was inversely related to the plasminogen activator inhibitor (PAI-1) and estrogen receptor (ER) expression but not the progesterone receptor (PR) and urokinase plasminogen activator (uPA). A low Tiam1 expression was associated with p53 positivity without being related to HER2/neu status. The data show that Tiam1 expression decreases with the progression of breast carcinomas and is inversely associated with several established breast tumor markers. Therefore, we suggest that Tiam1 counteracts the progression of breast carcinomas and is suitable as a novel breast tumor marker.

  12. Antiproliferative activity and induction of apoptotic by ethanolic extract of Alpinia galanga rhizhome in human breast carcinoma cell line

    PubMed Central

    2014-01-01

    Background We investigated the potential of galangal rhizomes to induce cytotoxic and apoptotic effects in the cultured human breast carcinoma cell line, (MCF-7) in compare with the non-malignant (MRC-5) cells. Methods Both cells were cultured in DMEM medium and treated with galangal rhizomes for three consecutive days. The percentage of apoptotic cells was determined by flow cytometry using Annexin-V fluorescein isothiocyanate. Results The results showed that the ethanolic extract of galangal rhizomes decreased cell viability in the malignant cells as a concentration- and time- dependent manner. The IC50 values against MCF-7 were determined at 400.0 ± 11.7 and 170.0 ± 5.9 μg/ml after 48 and 72 h respectively. The morphology of MCF-7 cells treated with the ethanolic extract confirmed the cell proliferation assay results. Alpinia galanga induced apoptosis in MCF-7 cells, as determined by flow cytometry. Conclusions We concluded that the extract of Alpinia galanga exerts pro-apoptotic effects in a breast cancer-derived cell line and could be considered as a potential chemotherapeutic agent in breast cancer. PMID:24935101

  13. Antiproliferative activity and induction of apoptotic by ethanolic extract of Alpinia galanga rhizhome in human breast carcinoma cell line.

    PubMed

    Samarghandian, Saeed; Hadjzadeh, Mousa-Al-Reza; Afshari, Jalil Tavakkol; Hosseini, Mohadeseh

    2014-06-17

    We investigated the potential of galangal rhizomes to induce cytotoxic and apoptotic effects in the cultured human breast carcinoma cell line, (MCF-7) in compare with the non-malignant (MRC-5) cells. Both cells were cultured in DMEM medium and treated with galangal rhizomes for three consecutive days. The percentage of apoptotic cells was determined by flow cytometry using Annexin-V fluorescein isothiocyanate. The results showed that the ethanolic extract of galangal rhizomes decreased cell viability in the malignant cells as a concentration- and time- dependent manner. The IC50 values against MCF-7 were determined at 400.0 ± 11.7 and 170.0 ± 5.9 μg/ml after 48 and 72 h respectively. The morphology of MCF-7 cells treated with the ethanolic extract confirmed the cell proliferation assay results. Alpinia galanga induced apoptosis in MCF-7 cells, as determined by flow cytometry. We concluded that the extract of Alpinia galanga exerts pro-apoptotic effects in a breast cancer-derived cell line and could be considered as a potential chemotherapeutic agent in breast cancer.

  14. Does Breast Magnetic Resonance Imaging Combined With Conventional Imaging Modalities Decrease the Rates of Surgical Margin Involvement and Reoperation?

    PubMed Central

    Lai, Hung-Wen; Chen, Chih-Jung; Lin, Ying-Jen; Chen, Shu-Ling; Wu, Hwa-Koon; Wu, Yu-Ting; Kuo, Shou-Jen; Chen, Shou-Tung; Chen, Dar-Ren

    2016-01-01

    Abstract The objective of this study was to assess whether preoperative breast magnetic resonance imaging (MRI) combined with conventional breast imaging techniques decreases the rates of margin involvement and reexcision. Data on patients who underwent surgery for primary operable breast cancer were obtained from the Changhua Christian Hospital (CCH) breast cancer database. The rate of surgical margin involvement and the rate of reoperation were compared between patients who underwent conventional breast imaging modalities (Group A: mammography and sonography) and those who received breast MRI in addition to conventional imaging (Group B: mammography, sonography, and MRI). A total of 1468 patients were enrolled in this study. Among the 733 patients in Group A, 377 (51.4%) received breast-conserving surgery (BCS) and 356 (48.6%) received mastectomy. Among the 735 patients in Group B, 348 (47.3%) received BCS and 387 (52.7%) received mastectomy. There were no significant differences in operative method between patients who received conventional imaging alone and those that received MRI and conventional imaging (P = 0.13). The rate of detection of pathological multifocal/multicentric breast cancer was markedly higher in patients who received preoperative MRI than in those who underwent conventional imaging alone (14.3% vs 8.6%, P < 0.01). The overall rate of surgical margin involvement was significantly lower in patients who received MRI (5.0%) than in those who received conventional imaging alone (9.0%) (P < 0.01). However, a significant reduction in rate of surgical margin positivity was only observed in patients who received BCS (Group A, 14.6%; Group B, 6.6%, P < 0.01). The overall BCS reoperation rates were 11.7% in the conventional imaging group and 3.2% in the combined MRI group (P < 0.01). There were no significant differences in rate of residual cancer in specimens obtained during reoperation between the 2 preoperative imaging groups

  15. ST6GALNAC5 Expression Decreases the Interactions between Breast Cancer Cells and the Human Blood-Brain Barrier.

    PubMed

    Drolez, Aurore; Vandenhaute, Elodie; Delannoy, Clément Philippe; Dewald, Justine Hélène; Gosselet, Fabien; Cecchelli, Romeo; Julien, Sylvain; Dehouck, Marie-Pierre; Delannoy, Philippe; Mysiorek, Caroline

    2016-08-11

    The ST6GALNAC5 gene that encodes an α2,6-sialyltransferase involved in the biosynthesis of α-series gangliosides, was previously identified as one of the genes that mediate breast cancer metastasis to the brain. We have shown that the expression of ST6GALNAC5 in MDA-MB-231 breast cancer cells resulted in the expression of GD1α ganglioside at the cell surface. By using a human blood-brain barrier in vitro model recently developed, consisting in CD34⁺ derived endothelial cells co-cultivated with pericytes, we show that ST6GALNAC5 expression decreased the interactions between the breast cancer cells and the human blood-brain barrier.

  16. ST6GALNAC5 Expression Decreases the Interactions between Breast Cancer Cells and the Human Blood-Brain Barrier

    PubMed Central

    Drolez, Aurore; Vandenhaute, Elodie; Delannoy, Clément Philippe; Dewald, Justine Hélène; Gosselet, Fabien; Cecchelli, Romeo; Julien, Sylvain; Dehouck, Marie-Pierre; Delannoy, Philippe; Mysiorek, Caroline

    2016-01-01

    The ST6GALNAC5 gene that encodes an α2,6-sialyltransferase involved in the biosynthesis of α-series gangliosides, was previously identified as one of the genes that mediate breast cancer metastasis to the brain. We have shown that the expression of ST6GALNAC5 in MDA-MB-231 breast cancer cells resulted in the expression of GD1α ganglioside at the cell surface. By using a human blood-brain barrier in vitro model recently developed, consisting in CD34+ derived endothelial cells co-cultivated with pericytes, we show that ST6GALNAC5 expression decreased the interactions between the breast cancer cells and the human blood-brain barrier. PMID:27529215

  17. Intensity-Modulated Radiotherapy Results in Significant Decrease in Clinical Toxicities Compared With Conventional Wedge-Based Breast Radiotherapy

    SciTech Connect

    Harsolia, Asif; Kestin, Larry; Grills, Inga; Wallace, Michelle; Jolly, Shruti; Jones, Cortney; Lala, Moinaktar; Martinez, Alvaro; Schell, Scott; Vicini, Frank A. . E-mail: fvicini@beaumont.edu

    2007-08-01

    Purpose: We have previously demonstrated that intensity-modulated radiotherapy (IMRT) with a static multileaf collimator process results in a more homogenous dose distribution compared with conventional wedge-based whole breast irradiation (WBI). In the present analysis, we reviewed the acute and chronic toxicity of this IMRT approach compared with conventional wedge-based treatment. Methods and Materials: A total of 172 patients with Stage 0-IIB breast cancer were treated with lumpectomy followed by WBI. All patients underwent treatment planning computed tomography and received WBI (median dose, 45 Gy) followed by a boost to 61 Gy. Of the 172 patients, 93 (54%) were treated with IMRT, and the 79 patients (46%) treated with wedge-based RT in a consecutive fashion immediately before this cohort served as the control group. The median follow-up was 4.7 years. Results: A significant reduction in acute Grade 2 or worse dermatitis, edema, and hyperpigmentation was seen with IMRT compared with wedges. A trend was found toward reduced acute Grade 3 or greater dermatitis (6% vs. 1%, p = 0.09) in favor of IMRT. Chronic Grade 2 or worse breast edema was significantly reduced with IMRT compared with conventional wedges. No difference was found in cosmesis scores between the two groups. In patients with larger breasts ({>=}1,600 cm{sup 3}, n = 64), IMRT resulted in reduced acute (Grade 2 or greater) breast edema (0% vs. 36%, p <0.001) and hyperpigmentation (3% vs. 41%, p 0.001) and chronic (Grade 2 or greater) long-term edema (3% vs. 30%, p 0.007). Conclusion: The use of IMRT in the treatment of the whole breast results in a significant decrease in acute dermatitis, edema, and hyperpigmentation and a reduction in the development of chronic breast edema compared with conventional wedge-based RT.

  18. Vitamin D Decreases Risk of Breast Cancer in Premenopausal Women of Normal Weight in Subtropical Taiwan

    PubMed Central

    Lee, Meei-Shyuan; Huang, Yi-Chen; Wahlqvist, Mark L; Wu, Tsai-Yi; Chou, Yu-Ching; Wu, Mei-Hsuan; Yu, Jyh-Cherng; Sun, Chien-An

    2011-01-01

    Background Evidence for an association between vitamin D status and breast cancer is now more convincing, but is uncertain in subtropical areas like Taiwan. This hospital-based case-control study examined the relationship of breast cancer with vitamin D intake and sunlight exposure. Methods A total of 200 incident breast cancer cases in a Taipei hospital were matched with 200 controls by date of interview and menopausal status. Information on risk factors for breast cancer was collected in face-to-face interviews and assessed with reference to vitamin D intake (foods and nutrients) and sunlight exposure. Vitamin D intake was divided into quartiles, and threshold effect was evaluated by comparing Q2–Q4 with Q1. Results After controlling for age, education, parity, hormone replacement therapy, body mass index (BMI), energy intake, menopausal status, and daily sunlight exposure, the risk of breast cancer in participants with a dietary vitamin D intake greater than 5 µg per day was significantly lower (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.24–0.97) than that of participants with an intake less than 2 µg per day. In analysis stratified by menopausal status and BMI, both dietary vitamin D and total vitamin D intakes were associated with a protective effect among premenopausal women. There was a significant linear trend for breast cancer risk and dietary vitamin D intake in premenopausal women (P = 0.02). In participants with a BMI lower than 24 kg/m2 (ie, normal weight), dietary vitamin D intake was inversely related to breast cancer risk (P for trend = 0.002), and a threshold effect was apparent (Q2–Q4 vs Q1: OR, 0.46; 95% CI, 0.23–0.90). Conclusions Vitamin D had a protective effect against breast cancer in premenopausal women of normal weight in subtropical Taiwan, especially an intake greater than 5 µg per day. PMID:21160130

  19. Vitamin D decreases risk of breast cancer in premenopausal women of normal weight in subtropical taiwan.

    PubMed

    Lee, Meei-Shyuan; Huang, Yi-Chen; Wahlqvist, Mark L; Wu, Tsai-Yi; Chou, Yu-Ching; Wu, Mei-Hsuan; Yu, Jyh-Cherng; Sun, Chien-An

    2011-01-01

    Evidence for an association between vitamin D status and breast cancer is now more convincing, but is uncertain in subtropical areas like Taiwan. This hospital-based case-control study examined the relationship of breast cancer with vitamin D intake and sunlight exposure. A total of 200 incident breast cancer cases in a Taipei hospital were matched with 200 controls by date of interview and menopausal status. Information on risk factors for breast cancer was collected in face-to-face interviews and assessed with reference to vitamin D intake (foods and nutrients) and sunlight exposure. Vitamin D intake was divided into quartiles, and threshold effect was evaluated by comparing Q2-Q4 with Q1. After controlling for age, education, parity, hormone replacement therapy, body mass index (BMI), energy intake, menopausal status, and daily sunlight exposure, the risk of breast cancer in participants with a dietary vitamin D intake greater than 5 µg per day was significantly lower (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.24-0.97) than that of participants with an intake less than 2 µg per day. In analysis stratified by menopausal status and BMI, both dietary vitamin D and total vitamin D intakes were associated with a protective effect among premenopausal women. There was a significant linear trend for breast cancer risk and dietary vitamin D intake in premenopausal women (P = 0.02). In participants with a BMI lower than 24 kg/m(2) (ie, normal weight), dietary vitamin D intake was inversely related to breast cancer risk (P for trend = 0.002), and a threshold effect was apparent (Q2-Q4 vs Q1: OR, 0.46; 95% CI, 0.23-0.90). Vitamin D had a protective effect against breast cancer in premenopausal women of normal weight in subtropical Taiwan, especially an intake greater than 5 µg per day.

  20. Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells.

    PubMed

    Liu, Jing; He, Chengwei; Zhou, Keyuan; Wang, Jingdong; Kang, Jing X

    2009-01-09

    Estrogen receptor (ER) antagonists have been widely used for breast cancer treatment, but the efficacy and drug resistance remain to be clinical concerns. The purpose of this study was to determine whether the extracts of coptis, an anti-inflammatory herb, improve the anticancer efficacy of ER antagonists. The results showed that the combined treatment of ER antagonists and the crude extract of coptis or its purified compound berberine conferred synergistic growth inhibitory effect on MCF-7 cells (ER+), but not on MDA-MB-231 cells (ER-). Similar results were observed in the combined treatment of fulvestrant, a specific aromatase antagonist. Analysis of the expression of breast cancer related genes indicated that EGFR, HER2, bcl-2, and COX-2 were significantly downregulated, while IFN-beta and p21 were remarkably upregulated by berberine. Our results suggest that coptis extracts could be promising adjuvant to ER antagonists in ER positive breast cancer treatment through regulating expression of multiple genes.

  1. An extract from berries of Aronia melanocarpa modulates the generation of superoxide anion radicals in blood platelets from breast cancer patients.

    PubMed

    Kedzierska, Magdalena; Olas, Beata; Wachowicz, Barbara; Stochmal, Anna; Oleszek, Wieslaw; Jeziorski, Arkadiusz; Piekarski, Janusz; Glowacki, Rafal

    2009-10-01

    Plant antioxidants protect cells against oxidative stress. Because oxidative stress (measured by different biomarkers) is observed in breast cancer patients, the aim of this study was to establish the effects of a polyphenol-rich extract of Aronia melanocarpa (final concentration of 50 microg/mL, 5 min, 37 degrees C) on superoxide anion radicals (O(2)(-*)) and glutathione (GSH) in platelets from patients with breast cancer and in a healthy group in vitro. Generation of O(2)(-*) in platelets before and after incubation with the extract was measured by cytochrome C reduction. Using HPLC, we determined the level of glutathione in blood platelets. We observed a statistically significant increase of biomarkers of oxidative stress such as O(2)(-*) and a decrease in GSH in platelets from patients with breast cancer compared with the healthy group. We showed that the extract from A. melanocarpa added to blood platelets significantly reduced the production of O(2)(-*) in platelets not only from the healthy group but also from patients with breast cancer. Considering the data presented in this study, we have demonstrated the protective role of the extract from A. melanocarpa in patients with breast cancer in vitro. Georg Thieme Verlag KG Stuttgart-New York.

  2. Decreased LRIG1 in fulvestrant-treated luminal breast cancer cells permits ErbB3 upregulation and increased growth.

    PubMed

    Morrison, M M; Williams, M M; Vaught, D B; Hicks, D; Lim, J; McKernan, C; Aurisicchio, L; Ciliberto, G; Simion, C; Sweeney, C; Cook, R S

    2016-03-03

    ErbB3, a member of the ErbB family of receptor tyrosine kinases, is a potent activator of phosphatidyl inositol-3 kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling, driving tumor cell survival and therapeutic resistance in breast cancers. In luminal breast cancers, ErbB3 upregulation following treatment with the antiestrogen fulvestrant enhances PI3K/mTOR-mediated cell survival. However, the mechanism by which ErbB3 is upregulated in fulvestrant-treated cells is unknown. We found that ErbB3 protein levels and cell surface presentation were increased following fulvestrant treatment, focusing our attention on proteins that regulate ErbB3 at the cell surface, including Nrdp1, NEDD4 and LRIG1. Among these, only LRIG1 correlated positively with ERα, but inversely with ErbB3 in clinical breast cancer data sets. LRIG1, an estrogen-inducible ErbB downregulator, was decreased in a panel of fulvestrant-treated luminal breast cancer cells. Ectopic LRIG1 expression from an estrogen-independent promoter uncoupled LRIG1 from estrogen regulation, thus sustaining LRIG1 and maintaining low ErbB3 levels in fulvestrant-treated cells. An LRIG1 mutant lacking the ErbB3 interaction motif was insufficient to downregulate ErbB3. Importantly, LRIG1 overexpression improved fulvestrant-mediated growth inhibition, whereas cells expressing the LRIG1 mutant were poorly sensitive to fulvestrant, despite effective ERα downregulation. Consistent with these results, LRIG1 expression correlated positively with increased disease-free survival in antiestrogen-treated breast cancer patients. These data suggest that ERα-dependent expression of LRIG1 dampens ErbB3 signaling in luminal breast cancer cells, and by blocking ERα activity with fulvestrant, LRIG1 is decreased thus permitting ErbB3 accumulation, enhanced ErbB3 signaling to cell survival pathways and blunting therapeutic response to fulvestrant.

  3. Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice*

    PubMed Central

    Song, Kai; Herzog, Brett H.; Fu, Jianxin; Sheng, Minjia; Bergstrom, Kirk; McDaniel, J. Michael; Kondo, Yuji; McGee, Samuel; Cai, Xiaofeng; Li, Ping; Chen, Hong; Xia, Lijun

    2015-01-01

    Mucin-type core 1-derived O-glycans, one of the major types of O-glycans, are highly expressed in mammary gland epithelium. Abnormal O-glycans such as Tn antigen are found in over 90% of breast cancers; however, the in vivo role of these aberrant O-glycans in the etiology of breast cancer is unclear. We generated mice with mammary epithelial specific deletion of core 1-derived O-glycans. By crossing with two spontaneous mouse breast cancer models, we determined that loss of core 1-derived O-glycans delays the onset and progression of breast cancer development. Deficiency of core 1 O-glycosylation impaired the localization of Muc1, a major O-glycoprotein, on the apical surfaces of mammary epithelium. Signaling mediated by Muc1, which is critical for breast cancer development, was also defective in the absence of core 1 O-glycans. This study reveals an unexpected role of core 1-derived O-glycans in breast cancer development in mice. PMID:26124270

  4. Histologic Grade and Decrease in Tumor Dimensions Affect Axillary Lymph Node Status after Neoadjuvant Chemotherapy in Breast Cancer Patients.

    PubMed

    Kim, Tae Hee; Kang, Doo Kyoung; Kim, Ji Young; Han, Sehwan; Jung, Yongsik

    2015-12-01

    The purposes our study was to find out any histologic factors associated with negative conversion of axillary lymph node (ALN) after neoadjuvant chemotherapy (NAC). We also evaluated the association between the decrease in size of primary breast tumor and negative conversion of ALN. From January 2012 to November 2014, we included 133 breast cancer patients who underwent NAC and who had ALN metastases which were confirmed on fine-needle aspiration or core needle biopsy at initial diagnosis. All 133 patients underwent initial magnetic resonance imaging (MRI) at the time of diagnosis and preoperative MRI after completion of NAC. We measured the longest dimension of primary breast cancer on MRI. Of 133 patients, 39 patients (29%) showed negative conversion of ALN and of these 39 patients, 25 patients (64%) showed pathologic complete remission of primary breast. On univariate analysis, mean percent decrease in longest dimension, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status and histologic grade were significantly associated with the ALN status after NAC (p<0.001, p=0.001, p< 0.001, p=0.001, p=0.002, respectively). On multivariate logistic regression analysis, percent decrease in longest dimension (odds ratio, 1.026; 95% confidence interval [CI], 1.009-1.044) and histologic grade (odds ratio, 3.964; 95% CI, 1.151-13.657) were identified as being independently associated with the ALN status after NAC. The area under the receiver operating characteristic curve was 0.835 with the best cutoff value of 80% decrease in longest dimension. Combination of high histologic grade and more than 80% decrease in longest dimension showed 64% sensitivity and 92% specificity. High histologic grade and more than 80% decrease in primary tumor dimension were associated with negative conversion of ALN after NAC.

  5. Dichloromethane and Methanol Extracts of Scrophularia oxysepala Induces Apoptosis in MCF-7 Human Breast Cancer Cells

    PubMed Central

    Valiyari, Samira; baradaran, behzad; Delazar, Abbas; Pasdaran, Ardalan; Zare, Fateme

    2012-01-01

    Purpose: Breast cancer is the most common cause of cancer-related death in women worldwide. Therefore, there is an urgent need to identify and develop therapeutic strategies against this deadly disease. This study is the first to investigate the cytotoxic effects and the mechanism of cell death of Scrophularia oxysepala extracts in MCF-7 human breast cancer cells. Methods: Three extracts of Scrophularia oxysepala including the n-hexane, dichloromethane and methanol extracts were examined. MTT (3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Trypan-blue assays were performed in MCF-7 cells as well as Human umbilical vein endothelial cells (HUVEC) to analyze the cytotoxic activity of the extracts of Scrophularia oxysepala. Further, the apoptosis inducing action of the extracts was determined by TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) test and cell death assay. Results: The results showed that the n-hexane extract had no cytotoxic effects but dichloromethane and methanol extracts significantly inhibited cell growth and viability in a dose and time dependent manner without inducing damage to non-cancerous cell line HUVEC. In addition, Cell death assay and DNA fragmentation analysis using TUNEL indicated induction of apoptosis by dichloromethane and methanol extracts of Scrophularia oxysepala in MCF-7 cells. Conclusion: Our studies suggest that this plant may contain potential bioactive compound(s) for the treatment of breast cancer. PMID:24312797

  6. Anti-cancer effect of Annona Muricata Linn Leaves Crude Extract (AMCE) on breast cancer cell line.

    PubMed

    Syed Najmuddin, Syed Umar Faruq; Romli, Muhammad Firdaus; Hamid, Muhajir; Alitheen, Noorjahan Banu; Nik Abd Rahman, Nik Mohd Afizan

    2016-08-24

    Annona muricata Linn which comes from Annonaceae family possesses many therapeutic benefits as reported in previous studies and to no surprise, it has been used in many cultures to treat various ailments including headaches, insomnia, and rheumatism to even treating cancer. However, Annona muricata Linn obtained from different cultivation area does not necessarily offer the same therapeutic effects towards breast cancer (in regards to its bioactive compound production). In this study, anti-proliferative and anti-cancer effects of Annona muricata crude extract (AMCE) on breast cancer cell lines were evaluated. A screening of nineteen samples of Annona muricata from different location was determined by MTT assay on breast cancer cell lines (MCF-7, MDA-MB-231, and 4 T1) which revealed a varied potency (IC50) amongst them. Then, based on the IC50 profile from the anti-proliferative assay, further downward assays such as cell cycle analysis, Annexin V/FITC, AO/PI, migration, invasion, and wound healing assay were performed only with the most potent leaf aqueous extract (B1 AMCE) on 4 T1 breast cancer cell line to investigate its anti-cancer effect. Then, the in vivo anti-cancer study was conducted where mice were fed with extract after inducing the tumor. At the end of the experiment, histopathology of tumor section, tumor nitric oxide level, tumor malondialdehyde level, clonogenic assay, T cell immunophenotyping, and proteome profiler analysis were performed. Annona muricata crude extract samples exhibited different level of cytotoxicity toward breast cancer cell lines. The selected B1 AMCE reduced the tumor's size and weight, showed anti-metastatic features, and induced apoptosis in vitro and in vivo of the 4 T1 cells. Furthermore, it decreased the level of nitric oxide and malondialdehyde in tumor while also increased the level of white blood cell, T-cell, and natural killer cell population. The results suggest that, B1 AMCE is a promising candidate for cancer

  7. Cytotoxic effects of Mangifera indica L. kernel extract on human breast cancer (MCF-7 and MDA-MB-231 cell lines) and bioactive constituents in the crude extract.

    PubMed

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Abdullah, Rasedee; Mirghani, Mohamed Elwathig Saeed; Al-Qubaisi, Mothanna

    2014-06-25

    Waterlily Mango (Mangifera indica L.) is thought to be antioxidant-rich, conferred by its functional phytochemicals. The potential anticancer effects of the ethanolic kernel extract on breast cancer cells (MDA-MB-231 and MCF-7) using MTT, anti-proliferation, neutral red (NR) uptake and lactate dehydrogenase (LDH) release assays were evaluated. Cytological studies on the breast cancer cells were also conducted, and phytochemical analyses of the extract were carried out to determine the likely bioactive compounds responsible for such effects. Results showed the extract induced cytotoxicity in MDA-MB-231 cells and MCF-7 cells with IC50 values of 30 and 15 μg/mL, respectively. The extract showed significant toxicity towards both cell lines, with low toxicity to normal breast cells (MCF-10A). The cytotoxic effects on the cells were further confirmed by the NR uptake, antiproliferative and LDH release assays. Bioactive analyses revealed that many bioactives were present in the extract although butylated hydroxytoluene, a potent antioxidant, was the most abundant with 44.65%. M. indica extract appears to be more cytoxic to both estrogen positive and negative breast cancer cell lines than to normal breast cells. Synergistic effects of its antioxidant bioactives could have contributed to the cytotoxic effects of the extract. The extract of M. indica, therefore, has potential anticancer activity against breast cancer cells. This potential is worth studying further, and could have implications on future studies and eventually management of human breast cancers.

  8. Cytotoxic effects of Mangifera indica L. kernel extract on human breast cancer (MCF-7 and MDA-MB-231 cell lines) and bioactive constituents in the crude extract

    PubMed Central

    2014-01-01

    Background Waterlily Mango (Mangifera indica L.) is thought to be antioxidant-rich, conferred by its functional phytochemicals. Methods The potential anticancer effects of the ethanolic kernel extract on breast cancer cells (MDA-MB-231 and MCF-7) using MTT, anti-proliferation, neutral red (NR) uptake and lactate dehydrogenase (LDH) release assays were evaluated. Cytological studies on the breast cancer cells were also conducted, and phytochemical analyses of the extract were carried out to determine the likely bioactive compounds responsible for such effects. Results Results showed the extract induced cytotoxicity in MDA-MB-231 cells and MCF-7 cells with IC50 values of 30 and 15 μg/mL, respectively. The extract showed significant toxicity towards both cell lines, with low toxicity to normal breast cells (MCF-10A). The cytotoxic effects on the cells were further confirmed by the NR uptake, antiproliferative and LDH release assays. Bioactive analyses revealed that many bioactives were present in the extract although butylated hydroxytoluene, a potent antioxidant, was the most abundant with 44.65%. Conclusions M. indica extract appears to be more cytoxic to both estrogen positive and negative breast cancer cell lines than to normal breast cells. Synergistic effects of its antioxidant bioactives could have contributed to the cytotoxic effects of the extract. The extract of M. indica, therefore, has potential anticancer activity against breast cancer cells. This potential is worth studying further, and could have implications on future studies and eventually management of human breast cancers. PMID:24962691

  9. Murraya koenigii leaf extract inhibits proteasome activity and induces cell death in breast cancer cells

    PubMed Central

    2013-01-01

    Background Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine. Here we show that Murraya koenigii leaves (curry leaves), a rich source of polyphenols, inhibit the proteolytic activity of the cancer cell proteasome, and cause cell death. Methods Hydro-methanolic extract of curry leaves (CLE) was prepared and its total phenolic content [TPC] determined by, the Folin-Ciocalteau’s method. Two human breast carcinoma cell lines: MCF-7 and MDA-MB-231 and a normal human lung fibroblast cell line, WI-38 were used for the studies. Cytotoxicity of the CLE was assessed by the MTT assay. We studied the effect of CLE on growth kinetics using colony formation assay. Growth arrest was assessed by cell cycle analysis and apoptosis by Annexin-V binding using flow cytometry. Inhibition of the endogenous 26S proteasome was studied in intact cells and cell extracts using substrates specific to 20S proteasomal enzymes. Results CLE decreased cell viability and altered the growth kinetics in both the breast cancer cell lines in a dose-dependent manner. It showed a significant arrest of cells in the S phase albeit in cancer cells only. Annexin V binding data suggests that cell death was via the apoptotic pathway in both the cancer cell lines. CLE treatment significantly decreased the activity of the 26S proteasome in the cancer but not normal cells. Conclusions Our study suggests M. koenigii leaves to be a potent source of proteasome inhibitors that lead to cancer cell death. Therefore, identification

  10. Momordica cochinchinensis Spreng. seed extract suppresses breast cancer growth by inducing cell cycle arrest and apoptosis.

    PubMed

    Zheng, Lei; Zhang, Yanmin; Liu, Yanping; Yang, Xiaoyan Ou; Zhan, Yingzhuan

    2015-10-01

    The herb Momordica cochinchinensis has been used for a variety of purposes, and been shown to have anti‑cancer properties. The present study assessed the potency and the underlying mechanisms of action of the ethyl acetate extract of seeds of Momordica cochinchinensis (ESMC2) on breast cancer cells. Therefore, the effects of ESMC2 on the cell viability, cell cycle and apoptosis of MDA‑MB‑231 cells were investigated. The results showed that ESMC2 exerted a marked growth inhibitory effect on the cells. Cell cycle arrest in G2 phase following treatment with ESMC2 was associated with a marked increase in the protein levels of cyclin B1, cyclin E and cyclin-dependent kinase 1 and a decrease in cyclin D1 expression. In addition, ESMC2 dose‑dependently induced cell apoptosis, which was mediated via upregulation of the apoptosis-associated proteins p53, B-cell lymphoma 2 (Bcl‑2)‑associated X protein, Bcl-2 homologous antagonist killer and Bcl-2-associated death promoter expression, as well as downregulation of nuclear factor kappa B, Bcl‑2 and myeloid cell leukemia‑1. Furthermore, the activation of extracellular signal-regulated kinase 1/2, p38, c-Jun N-terminal kinase (JNK) and Akt phosphorylation were decreased by ESMC2 in a dose‑dependent manner, indicating that ESMC2 exerted its effects via the mitogen-activated protein kinase/JNK pathway. Furthermore, nude mouse xenotransplant models were used to evaluate the tumor growth inhibitory effects of ESMC2. The possible chemical components of ESMC2 were analyzed by gas chromatography-mass spectrometry, and 12 compounds were detected from the major peaks based on the similarity index with entries of a compound database. The results of the present study may aid in the development of novel therapies for breast cancer.

  11. Awareness that early cancer lump is painless could decrease breast cancer mortality in developing countries.

    PubMed

    Garg, Pankaj

    2016-06-10

    There are several factors which contribute to patients' reporting late to healthcare facility even after detecting the breast lump (patient delay). Amongst these, one of the important factors in low- and middle-income countries is lack of awareness that early cancer lump is painless (ECLIPs). Pain is often taken as a danger sign and absence of pain is often not taken seriously. The studies have shown that up to 98% of women in low-income countries are unaware that a painless lump could be a warning sign of early breast cancer. This fact is significant because this could be one of the prime reasons for the women having discovered a painless lump in the breast, accidentally or by breast self-examination, presume it to be harmless and don't report early to health care facility. Therefore, creating awareness about ECLIPs could be an effective strategy to reduce mortality due to breast cancer in low- and middle-income countries. Moreover, unlike modifying risk factors which requires long term behavior modification, creating awareness about ECLIPs is easy and cost effective.

  12. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells

    PubMed Central

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-01-01

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the “Alba” variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy. PMID:27498973

  13. Polyphenol-rich strawberry extract (PRSE) shows in vitro and in vivo biological activity against invasive breast cancer cells.

    PubMed

    Amatori, Stefano; Mazzoni, Luca; Alvarez-Suarez, Josè Miguel; Giampieri, Francesca; Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Yuliett; Afrin, Sadia; Errico Provenzano, Alfredo; Persico, Giuseppe; Mezzetti, Bruno; Amici, Augusto; Fanelli, Mirco; Battino, Maurizio

    2016-08-08

    We describe the biological effects of a polyphenol-rich strawberry extract (PRSE), obtained from the "Alba" variety, on the highly aggressive and invasive basal-like breast cancer cell line A17. Dose-response and time-course experiments showed that PRSE is able to decrease the cellular viability of A17 cells in a time- and dose-dependent manner. PRSE effect on cell survival was investigated in other tumor and normal cell lines of both mouse and human origin, demonstrating that PRSE is more active against breast cancer cells. Cytofluorimetric analysis of A17 cells demonstrated that sub-lethal doses of PRSE reduce the number of cells in S phase, inducing the accumulation of cells in G1 phase of cell cycle. In addition, the migration of A17 cells was studied monitoring the ability of PRSE to inhibit cellular mobility. Gene expression analysis revealed the modulation of 12 genes playing different roles in the cellular migration, adhesion and invasion processes. Finally, in vivo experiments showed the growth inhibition of A17 cells orthotopically transplanted into FVB syngeneic mice fed with PRSE. Overall, we demonstrated that PRSE exerts important biological activities against a highly invasive breast cancer cell line both in vitro and in vivo suggesting the strawberry extracts as preventive/curative food strategy.

  14. MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer.

    PubMed

    Wolfe, Adam R; Bambhroliya, Arvind; Reddy, Jay P; Debeb, Bisrat G; Huo, Lei; Larson, Richard; Li, Li; Ueno, Naoto T; Woodward, Wendy A

    2016-06-01

    We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. MiR-33a expression was analyzed by reverse transcriptase-polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a-expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a-expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a-expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a-expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P=.0228, log-rank test). For breast cancer patients

  15. DECREASE IN DYNAMIC VISCOSITY AND AVERAGE MOLECULAR WEIGHT OF ALGINATE FROM LAMINARIA DIGITATA DURING ALKALINE EXTRACTION(1).

    PubMed

    Vauchel, Peggy; Arhaliass, Abdellah; Legrand, Jack; Kaas, Raymond; Baron, Régis

    2008-04-01

    Alginates are natural polysaccharides that are extracted from brown seaweeds and widely used for their rheological properties. The central step in the extraction protocol used in the alginate industry is the alkaline extraction, which requires several hours. In this study, a significant decrease in alginate dynamic viscosity was observed after 2 h of alkaline treatment. Intrinsic viscosity and average molecular weight of alginates from alkaline extractions 1-4 h in duration were determined, indicating depolymerization of alginates: average molecular weight decreased significantly during the extraction, falling by a factor of 5 between 1 and 4 h of extraction. These results suggested that reducing extraction time could enable preserving the rheological properties of the extracted alginates.

  16. Apple phytochemical extracts inhibit proliferation of estrogen-dependent and estrogen-independent human breast cancer cells through cell cycle modulation.

    PubMed

    Sun, Jie; Liu, Rui Hai

    2008-12-24

    Breast cancer is the most commonly diagnosed cancer in women in the United States. Dietary modification, particularly increased intake of fruits and vegetables, has been consistently associated with a reduced risk of various cancers, including breast cancer. Apples are a major source of dietary phytochemicals and flavonoids and possess potent antioxidant activity and antiproliferative activity in vitro. However, the molecular mechanisms of the anticancer properties of apple phytochemical extracts are not completely understood. In this study a possible mechanism by which apple extracts could inhibit cancer cell growth in vitro using estrogen-dependent MCF-7 and estrogen-independent MDA-MB-231 human breast cancer cell lines was analyzed. The data showed that apple phytochemical extracts significantly inhibited human breast cancer MCF-7 and MDA-MB-231 cell proliferation at concentrations of 10-80 mg/mL (p < 0.05). DNA flow cytometric analysis showed that apple extracts significantly induced G1 arrest in MCF-7 cells in a dose-dependent manner at concentrations >20 mg/mL (p < 0.05). At concentrations of 15, 30, and 50 mg/mL, apple extracts caused a greater increase in the G1/S ratio in MDA-MB-231 cells when compared with MCF-7 cells (p < 0.05). Cyclin D1 and Cdk4 proteins, the two major G1/S transit regulators, decreased in a dose-dependent manner after exposure to apple extracts. These results suggest that the antiproliferative activities of apple phytochemical extracts toward human breast cancer cells might be due to the modulation effects on cell cycle machinery.

  17. Breast reconstruction after mastectomy: does it decrease depression at the long-term?

    PubMed Central

    Derks, Eveline Anne-Jet; Torensma, Bart; Honig, Adriaan; Vrouenraets, Bartholomeus Cornelius

    2016-01-01

    Background Depression is associated with breast cancer survivors in 22%. Although breast reconstruction (BR) is intended to provide psychological improvements such as reducing depression, literature is inconclusive and without long-term follow-up. The objective is to evaluate the impact of BR after breast cancer related mastectomy on the long-term depression risk and assess predictive factors for depression. Methods Women who underwent a curative mastectomy between 1999 and 2009 were included. After a mean follow-up of more than 6 years after operation, the Beck Depression Inventory-13 (BDI-13) evaluated depressive symptoms. Multivariable regression analysis provided predictors for depression. Results A total of 139 patients, 34 (24.5%) with and 105 (75.5%) without BR, were analyzed. Seventy-seven patients (48.2%) were at high risk for mild (n=58), moderate (n=5) or severe (n=4) depression. There was a trend for slightly better BDI-13 outcomes for women who underwent BR (2 vs. 4; P=0.06). Living alone [odds ratio (OR): 2.16; P=0.04], low educational level (OR: 3.70; P<0.01) and adjuvant hormonal/endocrine-therapy (OR: 2.36; P=0.02) were associated with an increased depression risk. Conclusions BR has no clear influence on depressive symptoms on the long-term. Predictive factors should alert clinicians to assess depressive symptoms in specific breast cancer patients during follow-up. PMID:27563558

  18. Breast Ultrasound: Computer-Aided Diagnosis Approach to Improving Specificity and Decreasing Observer Variability

    DTIC Science & Technology

    1998-01-01

    requiring alteration of this plan . First, given the hectic pace of an active mammography clinic, radiologists did not consistently record their inputs...Management of solid breast nodules: what is the role of sonography? Radiology. 1995. 196: p. 14-15. 9. Venta , LA., et al, Sonographic evaluation of

  19. Morphine decreases the pro-angiogenic interaction between breast cancer cells and macrophages in vitro

    PubMed Central

    Khabbazi, Samira; Nassar, Zeyad D.; Goumon, Yannick; Parat, Marie-Odile

    2016-01-01

    Interactions between the various cell types that constitute a solid tumour are essential to the biology of the tumour. We evaluated the effect of morphine on the proangiogenic interaction taking place between macrophages and breast cancer cells in vitro. The conditioned medium (CM) from breast cancer cells co-cultured with macrophages elicited endothelial cell proliferation and tube formation. This effect was inhibited if the co-culture occurred in the presence of morphine. The CM from breast cancer cells or macrophages grown individually, whether or not prepared in the presence of morphine, was ineffective in stimulating EC proliferation or tube formation. Using a mouse antibody array, we identified several angiogenesis-regulating factors differentially expressed in the CM of co-cultured cells prepared in the presence or absence of morphine, amongst which interleukin (IL)-6, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)-A. VEGF was induced in both cell types by the co-culture and this was prevented by morphine in a non-naloxone reversible fashion. The effect of CM from co-cultured cells on endothelial tube formation, but not proliferation, was prevented by anti-VEGF neutralizing antibody. Our results indicate that morphine prevents, in part via modulating VEGF-A expression, the pro-angiogenic interaction between macrophages and breast cancer cells. PMID:27514308

  20. Tumour cell invasion into blood vessels is significantly related to breast cancer subtypes and decreased survival.

    PubMed

    Klingen, Tor A; Chen, Ying; Stefansson, Ingunn M; Knutsvik, Gøril; Collett, Karin; Abrahamsen, Anne L; Aase, Hildegunn; Aas, Hans; Aas, Turid; Wik, Elisabeth; Akslen, Lars A

    2017-04-01

    Vascular invasion in breast cancer is associated with increased risk of recurrence, metastases and death from disease. However, there are few studies discriminating between blood vessel invasion (BVI) and lymphatic vessel involvement (LVI). A population-based series of 282 breast cancers was examined (200 screen-detected and 82 interval patients) with respect to BVI and LVI in addition to basic features and molecular subtypes, using CD31 and D2-40 antibodies. This series is part of the prospective Norwegian Breast Cancer Screening Program. The frequency of LVI and BVI was 25% and 15%, respectively. BVI was associated with HER2-positive and basal-like tumours, and several features of aggressive breast cancer, whereas LVI showed weaker associations. BVI was the strongest factor to predict interval cancer presentation. BVI showed significant associations with recurrence-free survival and disease-specific survival in univariate and multivariate analyses, whereas LVI was not significant. Our findings indicate that BVI by tumour cells is strongly associated with aggressive tumour features including a basal-like phenotype, and BVI was an independent prognostic factor in contrast to what was found for LVI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Using Computer-extracted Image Phenotypes from Tumors on Breast MRI to Predict Breast Cancer Pathologic Stage

    PubMed Central

    Burnside, Elizabeth S.; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M.; Sutton, Elizabeth; Brandt, Kathleen R.; Whitman, Gary; Conzen, Suzanne; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl; Huang, Erich; Freymann, John; Kirby, Justin; Morris, Elizabeth; Giger, Maryellen

    2015-01-01

    Background To demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on MRI can accurately predict pathologic stage. Methods We used a dataset of de-identified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. We analyzed 91 biopsy-proven breast cancer cases with pathologic stage (stage I = 22; stage II = 58; stage III = 11) and surgically proven nodal status (negative nodes = 46, ≥ 1 positive node = 44, no nodes examined = 1). We characterized tumors by (a) radiologist measured size, and (b) CEIP. We built models combining two CEIPs to predict tumor pathologic stage and lymph node involvement, evaluated them in leave-one-out cross-validation with area under the ROC curve (AUC) as figure of merit. Results Tumor size was the most powerful predictor of pathologic stage but CEIPs capturing biologic behavior also emerged as predictive (e.g. stage I+II vs. III demonstrated AUC = 0.83). No size measure was successful in the prediction of positive lymph nodes but adding a CEIP describing tumor “homogeneity,” significantly improved this discrimination (AUC = 0.62, p=.003) over chance. Conclusions Our results indicate that MRI phenotypes show promise for predicting breast cancer pathologic stage and lymph node status. PMID:26619259

  2. Decreased Iron in Cancer Cells and Their Microenvironment Improves Cytolysis of Breast Cancer Cells by Natural Killer Cells.

    PubMed

    Jiang, Xian-Peng; Elliott, Robert L

    2017-05-01

    The association of iron with anticancer immunity is unclear. In order to determine the role of iron in anticancer immunity, we manipulated intracellular iron levels of the human MCF-7 and MDA-MB-231 breast cancer cell lines, and measured cytolysis of breast cancer cells by the natural killer cell line NK-92MI, nitric oxide (NO) production, tumor necrosis factor alpha (TNFα) production and gene expression of ferritin heavy chain (FTH1). We found that NK-92MI increased synthesis and release of NO and TNFα into the medium during co-culturing of NK-92MI cells with MCF-7 or MDA-MB-231 cells. Addition of iron inhibited the cytolysis of the breast cancer cell lines. The iron chelator deferoxamine (DFOM) increased NK-92MI cytolysis to MCF-7 or MDA-MB-231 cells. Iron reversed cytotoxicity to breast cancer cells induced by NO, released from S-nitroso-N-acetyl-penicillamine (NO donor). Real time quantitative polymerase chain reaction showed that iron up-regulated the expression of FTH1 and iron chelator DFOM reduced FTH1 expression of MCF-7 and MDA-MB-231 cells. In conclusion, increased iron in cancer cells and their microenvironment protects cancer cells from natural killer cell cytolysis by antagonizing NO- and TNFα-associated cytotoxicity and by up-regulation of ferritin expression in breast cancer cells. Conversely, a decrease in iron concentration caused by DFOM improves natural killer cytolysis of tumor cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Flavone inhibits migration through DLC1/RhoA pathway by decreasing ROS generation in breast cancer cells.

    PubMed

    Zhu, Wenzhen; Ma, Long; Yang, Bingwu; Zheng, Zhaodi; Chai, Rongfei; Liu, Tingting; Liu, Zhaojun; Song, Taiyu; Li, Fenglin; Li, Guorong

    2016-05-01

    Tumor suppressor protein deleted in liver cancer 1 (DLC1) is a RhoGTPase-activating protein (RhoGAP) and inhibits cancer cell migration by inactivating downstream target protein RhoA. A few studies have reported the regulations of reactive oxygen species (ROS) on RhoGAP. In this study, we investigated flavone (the core structure of flavonoids)-induced regulation on ROS generation and DLC1/RhoA pathway in MCF-7 and MDA-MB-231 breast cancer cells and explored whether flavone-induced upregulation of DLC1 is mediated by ROS. Our results showed that flavone decreased ROS production and inhibited cell migration through DLC1/RhoA pathway. To further investigate the role of ROS in flavone-induced regulation on DLC1/RhoA pathway, hydrogen peroxide was added to restore the ROS levels. Flavone-induced upregulation of DLC1 expression, downregulation of RhoA activity, and inhibition of cell migration were all restrained by hydrogen peroxide. We also found that flavone increased DLC1 stability by inhibiting DLC1 protein degradation in breast cancer cells. In summary, our study demonstrated that flavone inhibited cell migration through DLC1/RhoA pathway by decreasing ROS generation and suppressed DLC1 degradation in MCF-7 and MDA-MB-231 breast cancer cells.

  4. Black tea extract supplementation decreases oxidative damage in Jurkat T cells.

    PubMed

    Erba, D; Riso, P; Foti, P; Frigerio, F; Criscuoli, F; Testolin, G

    2003-08-15

    The purpose of this study was to investigate the protective effect of black tea (BT) extract against induced oxidative damage in Jurkat T-cell line. Cells supplemented with 10 or 25 mg/L BT were subjected to oxidation with ferrous ions. Malondialdehyde (MDA) production as marker of lipid peroxidation, DNA single strand breaks as marker of DNA damage, and modification of the antioxidant enzyme activity, glutathione peroxidase (GPX) were measured. Results show the efficacy of BT polyphenols to decrease DNA oxidative damage and to affect GPX activity (P<0.05), while no effect was shown on MDA production. The succeeding investigation of the activity of caffeine and epigallocatechin gallate demonstrated their antioxidant potential with respect to the cellular markers evaluated. In conclusion, this study supports the protective effect of BT against ferrous ions induced oxidative damage to DNA and the ability of BT to affect the enzyme antioxidant system of Jurkat cells.

  5. Ethanolic Extract of Algerian Propolis and Galangin Decreased Murine Melanoma T.

    PubMed

    Benguedouar, Lamia; Lahouel, Mesbah; Gangloff, Sophie C; Durlach, Anne; Grange, Florent; Bernard, Philippe; Antonicelli, Frank

    2016-01-01

    Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated.

  6. Surgeon performed continuous intraoperative ultrasound guidance decreases re-excisions and mastectomy rates in breast cancer.

    PubMed

    Karadeniz Cakmak, Guldeniz; Emre, Ali U; Tascilar, Oge; Bahadir, Burak; Ozkan, Selcuk

    2017-06-01

    Intraoperative ultrasound guided (IUG) breast conserving surgery (BCS) is being increasingly embraced by breast surgeons worldwide. We aimed to compare the efficacy of IUG-BCS for palpable and nonpalpable breast cancer with respect to margin status, re-excision rate, tissue sacrifice and cost-time analysis. Intraoperative localization protocol includes intraoperative ultrasound prior to excision to localize the lesion and guide the initial resection. The excised specimen was then examined visually and by palpation and the specimen and cavity was examined with ultrasound. Frozen sections were obtained routinely from a portion of all six faces of the resected specimen, and shaved cavity margins were sent for permanent histology. Of the 208 patients, 57.2% had nonpalpable tumors. The sensitivity of ultrasound localization was 100%. Negative margins were achieved in 92.43% of nonpalpable and 91.01% of palpable lesions at initial procedure. The involved margins were correctly identified by the surgeon via specimen sonography in 95.4% of cases. Final positive margin rate was 2.4%. Calculated resection ratio and time analysis revealed nothing significant. IUG-BCS is an invaluable and effective modality for obtaining clear surgical margins with optimum resection volumes and reducing re-operations. Furthermore, by means of this algorithm, in case of shaving cavity margins of the tumor bed for permanent analysis, frozen section evaluation might be omitted. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Green tea extracts reduce adipogenesis by decreasing expression of transcription factors C/EBPα and PPARγ

    PubMed Central

    Yang, Xiuling; Yin, Lei; Li, Tang; Chen, Zhihong

    2014-01-01

    Objectives: This study is to determine if green tea (Camellia sinensis) extracts (GTE) affects adipogenesis and further investigate the related molecular mechanisms. Methods: Patients with metabolic syndrome were recruited in this study. Of them, 70 patients received GTE and 64 received water to serve as the control group. The human serum adiponectin, visfatin, and leptin concentrations were determined by enzyme-linked immunosorbent assay. Adipogenesis of 3T3-L1 preadipocytes was induced with reagents and then the cells were treated with GTE. The lipids were stained with Oil Red O for analysis of adipogenesis of 3T3-L1 preadipocytes. The 3T3-L1 preadipocytes were treated with increasing concentrations (0.2-0.5%, w/v) of GTE for 2 days and the cell viability was determined by MTT assay. Reverse transcription real-time PCR and immunoblotting assays were performed to determine RNA and protein levels of relative molecules. Results: GTE increases the serum concentrations of adiponectin but decreases visfatin levels in patients received GTE. The leptin concentrations in serum were not significantly affected. The GTE reduces the adipogenesis-induced lipid accumulation in 3T3-L1 preadipocytes. GTE decreases the mRNA and protein expression of adipogenic transcription factors C/EBPα and PPARγ in 3T3-L1 cells. Expression levels of the adipocyte-specific genes encoding adipocyte protein 2, lipoprotein lipase, and glucose transporter 4 were also decreased by GTE. Furthermore, it was found that GTE reduces phosphorylation of Akt during adipocyte differentiation. Conclusions: GTE reduces adipogenesis by decreasing expression of transcription factors C/EBPα and PPARγ by reduction of phosphorylation of Akt during adipocyte differentiation. PMID:25663987

  8. Effects of the commercial extract of aronia on oxidative stress in blood platelets isolated from breast cancer patients after the surgery and various phases of the chemotherapy.

    PubMed

    Kedzierska, Magdalena; Olas, Beata; Wachowicz, Barbara; Glowacki, Rafal; Bald, Edward; Czernek, Urszula; Szydłowska-Pazera, Katarzyna; Potemski, Piotr; Piekarski, Janusz; Jeziorski, Arkadiusz

    2012-03-01

    Since the extract from berries of Aronia melanocarpa presents antioxidative properties in plasma and in blood platelets, not only from healthy group, but also from patients with benign breast diseases and in patients with invasive breast cancer before surgery, the aim of our present study was to evaluate the oxidative stress by measuring the level of various biomarkers of this process such as the generation of superoxide anion radicals (O(2)(-·)), the amount of carbonyl groups and 3-nitrotyrosine in proteins or the amount of glutathione in blood platelets isolated from breast cancer patients after the surgery and after various phases of the chemotherapy in the presence of A. melanocarpa extract (Aronox) in vitro. We demonstrated in platelet proteins from patients with invasive breast cancer (after the surgery and after various phases of the chemotherapy) higher level of carbonyl groups than in control healthy group. The level of 3-nitrotyrosine in platelet proteins from patients with invasive breast cancer was also significantly higher than in healthy subject group. We observed an increase of other biomarkers of oxidative stress such as O(2)(-·) and a decrease of GSH in platelets from patients with breast cancer (after the surgery and after various phases of the chemotherapy) compared to the healthy group. In model system in vitro our results showed that the commercial extract from berries of A. melanocarpa due to antioxidant action, significantly reduced the oxidative/nitrative stress in platelets from patients with invasive breast cancer caused by the surgery and various phases of the chemotherapy. Published by Elsevier B.V.

  9. Rationale of the BREAst cancer e-healTH [BREATH] multicentre randomised controlled trial: An Internet-based self-management intervention to foster adjustment after curative breast cancer by decreasing distress and increasing empowerment

    PubMed Central

    2012-01-01

    Background After completion of curative breast cancer treatment, patients go through a transition from patient to survivor. During this re-entry phase, patients are faced with a broad range of re-entry topics, concerning physical and emotional recovery, returning to work and fear of recurrence. Standard and easy-accessible care to facilitate this transition is lacking. In order to facilitate adjustment for all breast cancer patients after primary treatment, the BREATH intervention is aimed at 1) decreasing psychological distress, and 2) increasing empowerment, defined as patients’ intra- and interpersonal strengths. Methods/design The non-guided Internet-based self-management intervention is based on cognitive behavioural therapy techniques and covers four phases of recovery after breast cancer (Looking back; Emotional processing; Strengthening; Looking ahead). Each phase of the fully automated intervention has a fixed structure that targets consecutively psychoeducation, problems in everyday life, social environment, and empowerment. Working ingredients include Information (25 scripts), Assignment (48 tasks), Assessment (10 tests) and Video (39 clips extracted from recorded interviews). A non-blinded, multicentre randomised controlled, parallel-group, superiority trial will be conducted to evaluate the effectiveness of the BREATH intervention. In six hospitals in the Netherlands, a consecutive sample of 170 will be recruited of women who completed primary curative treatment for breast cancer within 4 months. Participants will be randomly allocated to receive either usual care or usual care plus access to the online BREATH intervention (1:1). Changes in self-report questionnaires from baseline to 4 (post-intervention), 6 and 10 months will be measured. Discussion The BREATH intervention provides a psychological self-management approach to the disease management of breast cancer survivors. Innovative is the use of patients’ own strengths as an explicit

  10. Estrogens decrease {gamma}-ray-induced senescence and maintain cell cycle progression in breast cancer cells independently of p53

    SciTech Connect

    Toillon, Robert-Alain . E-mail: robert.toillon@univ-lille1.fr; Magne, Nicolas; Laios, Ioanna; Castadot, Pierre; Kinnaert, Eric; Van Houtte, Paul; Desmedt, Christine B.Sc.; Leclercq, Guy; Lacroix, Marc

    2007-03-15

    Purpose: Sequential administration of radiotherapy and endocrine therapy is considered to be a standard adjuvant treatment of breast cancer. Recent clinical reports suggest that radiotherapy could be more efficient in association with endocrine therapy. The aim of this study was to evaluate the estrogen effects on irradiated breast cancer cells (IR-cells). Methods and Materials: Using functional genomic analysis, we examined the effects of 17-{beta}-estradiol (E{sub 2}, a natural estrogen) on MCF-7 breast cancer cells. Results: Our results showed that E{sub 2} sustained the growth of IR-cells. Specifically, estrogens prevented cell cycle blockade induced by {gamma}-rays, and no modification of apoptotic rate was detected. In IR-cells we observed the induction of genes involved in premature senescence and cell cycle progression and investigated the effects of E{sub 2} on the p53/p21{sup waf1/cip1}/Rb pathways. We found that E{sub 2} did not affect p53 activation but it decreased cyclin E binding to p21{sup waf1/cip1} and sustained downstream Rb hyperphosphorylation by functional inactivation of p21{sup waf1/cip1}. We suggest that Rb inactivation could decrease senescence and allow cell cycle progression in IR-cells. Conclusion: These results may help to elucidate the molecular mechanism underlying the maintenance of breast cancer cell growth by E{sub 2} after irradiation-induced damage. They also offer clinicians a rational basis for the sequential administration of ionizing radiation and endocrine therapies.

  11. Decrease in the antioxidant capacity in beverages containing tea extracts during storage.

    PubMed

    Nekvapil, Tomas; Kopriva, Vladimir; Boudny, Vladimir; Hostovsky, Martin; Dvorak, Petr; Malota, Ladislav

    2012-01-01

    The aim of this work was to determine antioxidant capacity of beverages containing black, white, and green tea extracts using the photochemiluminescence method, and to monitor its changes based on the storage temperature and time. Samples were stored at two different temperatures (refrigerated at 4°C and laboratory temperature 22°C), analyzed after opening of the original package, and consequently after 4 and 7 days. Results of the antioxidant capacity are expressed as the standard equivalents, that is, ascorbic acid in mmol/L. The highest mean value of the antioxidant capacity was found after opening of the original package in fruit-juice-enriched samples and totaled 9.793 mmol/L. This group revealed significant dependence (P < 0.05) not only on the storage time, but also temperature. In samples without added fruit juices containing preservatives the value was 0.428 mmol/L. This group showed significant dependence (P < 0.05) on the decrease of antioxidant capacity only when based on the storage time. Samples without fruit juices or preservatives showed significant decrease in the antioxidant capacity (P < 0.05) after 4 days of storage based on the storage time. The dependence on temperature was revealed only after 7 days of storage.

  12. Decrease in the Antioxidant Capacity in Beverages Containing Tea Extracts during Storage

    PubMed Central

    Nekvapil, Tomas; Kopriva, Vladimir; Boudny, Vladimir; Hostovsky, Martin; Dvorak, Petr; Malota, Ladislav

    2012-01-01

    The aim of this work was to determine antioxidant capacity of beverages containing black, white, and green tea extracts using the photochemiluminescence method, and to monitor its changes based on the storage temperature and time. Samples were stored at two different temperatures (refrigerated at 4°C and laboratory temperature 22°C), analyzed after opening of the original package, and consequently after 4 and 7 days. Results of the antioxidant capacity are expressed as the standard equivalents, that is, ascorbic acid in mmol/L. The highest mean value of the antioxidant capacity was found after opening of the original package in fruit-juice-enriched samples and totaled 9.793 mmol/L. This group revealed significant dependence (P < 0.05) not only on the storage time, but also temperature. In samples without added fruit juices containing preservatives the value was 0.428 mmol/L. This group showed significant dependence (P < 0.05) on the decrease of antioxidant capacity only when based on the storage time. Samples without fruit juices or preservatives showed significant decrease in the antioxidant capacity (P < 0.05) after 4 days of storage based on the storage time. The dependence on temperature was revealed only after 7 days of storage. PMID:22997491

  13. Glycone-rich Soy Isoflavone Extracts Promote Estrogen Receptor Positive Breast Cancer Cell Growth.

    PubMed

    Johnson, Kailee A; Vemuri, Sravan; Alsahafi, Sameerh; Castillo, Rudy; Cheriyath, Venugopalan

    2016-01-01

    Due to the association of hormone replacement therapy (HRT) with breast cancer risk, estrogenically active soy isoflavones are considered as an HRT alternative to alleviate menopausal symptoms. However, several recent reports challenged the health benefits of soy isoflavones and associated them with breast cancer promotion. While glyconic isoflavones are the major constituents of soybean seeds, due to their low cell permeability, they are considered to be biologically inactive. The glyconic isoflavones may exert their effects on membrane-bound estrogen receptors or could be converted to aglycones by extracellular β-glucosidases. Therefore, we hypothesized that despite their low cell permeability, soybean cultivars with high glyconic isoflavones may promote breast cancer cell growth. To test this, composition and estrogenic activity of isoflavones from 54 commercial soybean cultivars were determined. Soybean seeds produced in identical climate and growth conditions were used to minimize the effects of extraneous factors on isoflavone profile and concentrations. The glyconic daidzin concentration negatively correlated with genistin and with other aglycones. Relative to control, isoflavone extracts from 51 cultivars were estrogenic and promoted the growth of estrogen receptor positive (ER+) breast cancer cell line MCF-7 from 1.14 to 4.59 folds and other three cultivars slightly reduced the growth. Among these, extracts from three cultivars were highly estrogenic and promoted MCF-7 cell growth by 2.59-4.64 folds (P<0.005). Among six isoflavones, daidzin was positively associated with MCF-7 cell growth (P<0.005, r = 0.13966), whereas the negative correlation between genistin and MCF-7 cell growth was nearly significant (P≤0.0562, r = -0.026141). Furthermore, in drug interaction studies daidzin-rich isoflavone extracts antagonized tamoxifen, an ER inhibitor. Taken together, our results suggest that the glyconic daidzin-rich soy isoflavone extracts may exert estrogenic

  14. Cytotoxicity screening of Melastoma malabathricum extracts on human breast cancer cell lines in vitro

    PubMed Central

    Roslen, Nurfariza Ahmad; Alewi, Nur Aizura Mat; Ahamada, Hadji; Rasad, Mohammad Syaiful Bahari Abdull

    2014-01-01

    Objective To screen the cytotoxic activity of Melastoma malabathricum (M. malabathricum) against human breast cancer cell line (MCF-7) in vitro. Methods A three steps extraction protocol using n-hexane, chloroform and methanol as the solvents systems was carried out on leaves, stems and flowers of M. malabathricum. Dimethyl sulfoxide was used in extracts dilution and serial dilutions were conducted to obtain five different extract concentrations (100 µg/mL, 50 µg/mL, 25 µg/mL, 12.5 µg/mL and 6.25 µg/mL). The evaluation of cell growth was determined using methylene blue assay. Results Methanol extract from the leaves showed significant anticancer activity against MCF-7 cell lines with the IC50 value of 7.14 µg/ml while methanol and chloroform extract from the flowers exhibited a moderate activity towards MCF-7 cell line with the IC50 value of 33.63 µg/mL and 45.76 µg/mL respectively after 72 h of treatment. Conclusions The extracts from leaves and flowers of M. malabathricum showed promising anticancer activity toward human breast cancer cell lines with the lowest IC50 at 7.14 µg/mL while the extracts from stems showed less growth inhibition activity. PMID:25183274

  15. Cytotoxic Activity of Piper cubeba Extract in Breast Cancer Cell Lines

    PubMed Central

    Graidist, Potchanapond; Martla, Mananya; Sukpondma, Yaowapa

    2015-01-01

    This study aimed to evaluate the cytotoxicity of a crude extract of Piper cubeba against normal and breast cancer cell lines. To prepare the extract, P. cubeba seeds were ground, soaked in methanol and dichloromethane and isolated by column chromatography. Fractions were tested for cytotoxicity effects on normal fibroblast (L929), normal breast (MCF-12A) and breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The most effective fraction was selected for DNA fragmentation assay to detect apoptotic activity. The results showed that the methanolic crude extract had a higher cytotoxic activity against MDA-MB-468 and MCF-7 than a dichloromethane crude extract. Then, the methanolic crude extract was separated into six fractions, designated A to F. Fraction C was highly active against breast cancer cell lines with an IC50 value less than 4 μg/mL. Therefore, Fraction C was further separated into seven fractions, CA to CG. The 1H-NMR profile showed that Fraction CE was long chain hydrocarbons. Moreover, Fraction CE demonstrated the highest activity against MCF-7 cells with an IC50 value of 2.69 ± 0.09 μg/mL and lower cytotoxicity against normal fibroblast L929 cells with an IC50 value of 4.17 ± 0.77 μg/mL. Finally, DNA fragmentation with a ladder pattern characteristic of apoptosis was observed in MCF-7, MDA-MB-468, MDA-MB-231 and L929 cells, but not in MCF-12A cells. PMID:25867951

  16. Cytotoxic activity of Piper cubeba extract in breast cancer cell lines.

    PubMed

    Graidist, Potchanapond; Martla, Mananya; Sukpondma, Yaowapa

    2015-04-10

    This study aimed to evaluate the cytotoxicity of a crude extract of Piper cubeba against normal and breast cancer cell lines. To prepare the extract, P. cubeba seeds were ground, soaked in methanol and dichloromethane and isolated by column chromatography. Fractions were tested for cytotoxicity effects on normal fibroblast (L929), normal breast (MCF-12A) and breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The most effective fraction was selected for DNA fragmentation assay to detect apoptotic activity. The results showed that the methanolic crude extract had a higher cytotoxic activity against MDA-MB-468 and MCF-7 than a dichloromethane crude extract. Then, the methanolic crude extract was separated into six fractions, designated A to F. Fraction C was highly active against breast cancer cell lines with an IC50 value less than 4 μg/mL. Therefore, Fraction C was further separated into seven fractions, CA to CG. The 1H-NMR profile showed that Fraction CE was long chain hydrocarbons. Moreover, Fraction CE demonstrated the highest activity against MCF-7 cells with an IC50 value of 2.69 ± 0.09 μg/mL and lower cytotoxicity against normal fibroblast L929 cells with an IC50 value of 4.17 ± 0.77 μg/mL. Finally, DNA fragmentation with a ladder pattern characteristic of apoptosis was observed in MCF-7, MDA-MB-468, MDA-MB-231 and L929 cells, but not in MCF-12A cells.

  17. Phellinus linteus extract induces autophagy and synergizes with 5-fluorouracil to inhibit breast cancer cell growth.

    PubMed

    Lee, Wen-Ying; Hsu, Keng-Fu; Chiang, Tai-An; Chen, Chee-Jen

    2015-01-01

    Phellinus linteus (PL) is a medicinal mushroom due to its several biological properties, including anticancer activity. However, the mechanisms of its anticancer effect remain to be elucidated. We evaluated the inhibitory effects of the ethanolic extract from the PL combined with 5-FU on MDA-MB-231 breast cancer cell line and to determine the mechanism of cell death. Individually, PL extract and 5-FU significantly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner. PL extract (30 mg/mL) in combination with 5-FU (10 μg/mL) synergistically inhibited MDA-MB-231 cells by 1.8-fold. PL did not induce apoptosis, as demonstrated by the DNA fragmentation assay, the sub-G1 population, and staining with annexin V-FITC and propidium iodide. The exposure of MDA-MB-231 cells to PL extracts resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine staining, the formation of acidic vesicular organelles, autophagosome membrane association of microtubule-associated protein light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, and ultrastructural observation of autophagic vacuoles by transmission electron microscopy. We concluded that PL extracts synergized with low doses of 5-FU to inhibit triple-negative breast cancer cell growth and demonstrated that PL extract can induce autophagy-related cell death.

  18. Using computer-extracted image phenotypes from tumors on breast magnetic resonance imaging to predict breast cancer pathologic stage.

    PubMed

    Burnside, Elizabeth S; Drukker, Karen; Li, Hui; Bonaccio, Ermelinda; Zuley, Margarita; Ganott, Marie; Net, Jose M; Sutton, Elizabeth J; Brandt, Kathleen R; Whitman, Gary J; Conzen, Suzanne D; Lan, Li; Ji, Yuan; Zhu, Yitan; Jaffe, Carl C; Huang, Erich P; Freymann, John B; Kirby, Justin S; Morris, Elizabeth A; Giger, Maryellen L

    2016-03-01

    The objective of this study was to demonstrate that computer-extracted image phenotypes (CEIPs) of biopsy-proven breast cancer on magnetic resonance imaging (MRI) can accurately predict pathologic stage. The authors used a data set of deidentified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. In total, 91 biopsy-proven breast cancers were analyzed from patients who had information available on pathologic stage (stage I, n = 22; stage II, n = 58; stage III, n = 11) and surgically verified lymph node status (negative lymph nodes, n = 46; ≥ 1 positive lymph node, n = 44; no lymph nodes examined, n = 1). Tumors were characterized according to 1) radiologist-measured size and 2) CEIP. Then, models were built that combined 2 CEIPs to predict tumor pathologic stage and lymph node involvement, and the models were evaluated in a leave-1-out, cross-validation analysis with the area under the receiver operating characteristic curve (AUC) as the value of interest. Tumor size was the most powerful predictor of pathologic stage, but CEIPs that captured biologic behavior also emerged as predictive (eg, stage I and II vs stage III demonstrated an AUC of 0.83). No size measure was successful in the prediction of positive lymph nodes, but adding a CEIP that described tumor "homogeneity" significantly improved discrimination (AUC = 0.62; P = .003) compared with chance. The current results indicate that MRI phenotypes have promise for predicting breast cancer pathologic stage and lymph node status. Cancer 2016;122:748-757. © 2015 American Cancer Society. © 2015 American Cancer Society.

  19. Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer's disease animal model.

    PubMed

    Dhanasekaran, Muralikrishnan; Holcomb, Leigh A; Hitt, Angie R; Tharakan, Binu; Porter, Jami W; Young, Keith A; Manyam, Bala V

    2009-01-01

    PSAPP mice expressing the 'Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid beta plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) starting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid beta 1-40 and 1-42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid beta pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease. Copyright 2008 John Wiley & Sons, Ltd.

  20. Rice Hull Extract Suppresses Benign Prostate Hyperplasia by Decreasing Inflammation and Regulating Cell Proliferation in Rats.

    PubMed

    Kim, Chae-Yun; Chung, Kyung-Sook; Cheon, Se-Yun; Lee, Jong-Hyun; Park, Youn-Bum; An, Hyo-Jin

    2016-08-01

    Even though rice hull has various physiological functions with high antioxidant potential, the molecular mechanism(s) underlying the effects of rice hull on benign prostatic hyperplasia (BPH) have not been evaluated. The aim of this study was to determine the protective effect of rice hull water extract (RHE) against BPH, which is a common disorder in elderly men and involves inflammation that induces an imbalance between cell proliferation and cell death. In this study, RHE-treated mice exhibited lower prostate weights and ratios of prostate weight to body weight compared to those for the BPH-induced group. In addition, RHE-treated mice had lower serum levels of dihydrotestosterone, mRNA expression of 5α-reductase2, and protein expressions of proliferating cell nuclear antigen (PCNA). Furthermore, RHE treatment significantly decreased cell proliferation by regulating the expression levels of inflammatory-related proteins (iNOS and COX-2) and apoptosis-associated proteins (Fas, FADD, procaspase-8, -3, and Bcl-2 family proteins). These results suggest that RHE could protect against the development of BPH through its anti-inflammatory and apoptotic properties and has good potential as a treatment for BPH.

  1. Abarema cochliacarpos extract decreases the inflammatory process and skeletal muscle injury induced by Bothrops leucurus venom.

    PubMed

    Saturnino-Oliveira, Jeison; Santos, Daiana Do Carmo; Guimarães, Adriana Gibara; Santos Dias, Antônio; Tomaz, Marcelo Amorim; Monteiro-Machado, Marcos; Estevam, Charles Santos; De Lucca Júnior, Waldecy; Maria, Durvanei Augusto; Melo, Paulo A; Araújo, Adriano Antunes de Souza; Santos, Márcio Roberto Viana; Almeida, Jackson Roberto Guedes da Silva; Oliveira, Rita de Cássia Meneses; Pereira de Oliveira, Aldeidia; Quintans Júnior, Lucindo José

    2014-01-01

    Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation.

  2. Abarema cochliacarpos Extract Decreases the Inflammatory Process and Skeletal Muscle Injury Induced by Bothrops leucurus Venom

    PubMed Central

    Saturnino-Oliveira, Jeison; Santos, Daiana Do Carmo; Guimarães, Adriana Gibara; Santos Dias, Antônio; Tomaz, Marcelo Amorim; Monteiro-Machado, Marcos; Estevam, Charles Santos; Lucca Júnior, Waldecy De; Maria, Durvanei Augusto; Melo, Paulo A.; Araújo, Adriano Antunes de Souza; Santos, Márcio Roberto Viana; Almeida, Jackson Roberto Guedes da Silva; Oliveira, Rita de Cássia Meneses; Pereira de Oliveira, Aldeidia; Quintans Júnior, Lucindo José

    2014-01-01

    Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation. PMID:25136627

  3. Effect of pH and postmortem aging on protein extraction from broiler breast muscle.

    PubMed

    Eady, M; Samuel, D; Bowker, B

    2014-07-01

    This study determined the effects of extraction buffer pH and postmortem aging on the extraction of salt-soluble and water-soluble proteins from broiler pectoralis muscle. Deboned broiler breast fillets were collected at 4 h postmortem, packaged, and then stored at 4°C until 1, 5, or 8 d postmortem. After the designated aging period, salt-soluble and water-soluble protein extractions were performed using buffers at 7 different pH levels (pH 5.4, 6.4, 6.9, 7.2, 7.5, 8.0, 9.0). Protein concentrations of the extracts were measured and SDS-PAGE analysis was performed. Salt-soluble protein concentration increased (P < 0.0001) as buffer pH increased from pH 5.4 to 6.9 and then remained unchanged from pH 6.9 to 9.0. Water-soluble protein concentration increased (P < 0.0001) as buffer pH increased from pH 5.4 to 7.2 and then remained unchanged from pH 7.2 to 9.0. There was not a significant extraction buffer pH by aging treatment interaction for the total protein concentration of either the salt-soluble or water-soluble protein extracts. The protein concentrations of salt-soluble extracts were similar at both 1 and 8 d postmortem but lower (P < 0.0001) at 5 d postmortem. The protein concentrations of water-soluble extracts were similar at both 1 and 5 d postmortem, but higher (P < 0.0001) at 8 d. Both extraction buffer pH and postmortem aging influenced the SDS-PAGE protein profiles of salt-soluble and water-soluble protein extracts from breast muscles. Data demonstrate that postmortem aging and extraction buffer pH influence both the total amount and the composition of the myofibrillar and sarcoplasmic proteins that can be extracted from broiler breast fillets. © 2014 Poultry Science Association Inc.

  4. Antitumor evaluation of two selected Pakistani plant extracts on human bone and breast cancer cell lines.

    PubMed

    Engel, Nadja; Ali, Iftikhar; Adamus, Anna; Frank, Marcus; Dad, Akber; Ali, Sajjad; Nebe, Barbara; Atif, Muhammad; Ismail, Muhammad; Langer, Peter; Ahmad, Viqar Uddin

    2016-07-26

    The medicinal plants Vincetoxicum arnottianum (VSM), Berberis orthobotrys (BORM), Onosma hispida (OHRM and OHAM) and Caccinia macranthera (CMM) are used traditionally in Pakistan and around the world for the treatment of various diseases including cancer, dermal infections, uterine tumor, wounds etc. The present study focuses on the investigation of the selected Pakistani plants for their potential as anticancer agents on human bone and breast cancer cell lines in comparison with non-tumorigenic control cells. The antitumor evaluation was carried out on human bone (MG-63, Saos-2) and breast cancer cell lines (MCF-7, BT-20) in contrast to non-tumorigenic control cells (POB, MCF-12A) via cell viability measurements, cell cycle analysis, Annexin V/PI staining, microscopy based methods as well as migration/invasion determination, metabolic live cell monitoring and western blotting. After the first initial screening of the plant extracts, two extracts (BORM, VSM) revealed the highest potential with regard to its antitumor activity. Both extracts caused a significant reduction of cell viability in the breast and bone cancer cells in a concentration dependent manner. The effect of VSM is achieved primarily by inducing a G2/M arrest in the cell cycle and the stabilization of the actin stress fibers leading to reduced cell motility. By contrast BORM's cytotoxic properties were caused through the lysosomal-mediated cell death pathway indicated by an upregulation of Bcl-2 expression. The antitumor evaluation of certain medicinal plants presented in this study identified the methanolic root extract of Berberis orthobotrys and the methanolic extract of Vincetoxicum arnottianum as promising sources for exhibiting the antitumor activity. Therefore, the indigenous use of the herbal remedies for the treatment of cancer and cancer-related diseases has a scientific basis. Moreover, the present study provides a base for phytochemical investigation of the plant extracts.

  5. The Expression of the Zonula Adhaerens Protein PLEKHA7 Is Strongly Decreased in High Grade Ductal and Lobular Breast Carcinomas

    PubMed Central

    Tille, Jean-Christophe; Ho, Liza; Shah, Jimit; Seyde, Olivia; McKee, Thomas A.; Citi, Sandra

    2015-01-01

    PLEKHA7 is a junctional protein, which participates in a complex that stabilizes E-cadherin at the zonula adhaerens. Since E-cadherin is involved in epithelial morphogenesis, signaling, and tumor progression, we explored PLEKHA7 expression in cancer. PLEKHA7 expression was assessed in invasive ductal and lobular carcinomas of the breast by immunohistochemistry, immunofluorescence and quantitative RT-PCR. PLEKHA7 was detected at epithelial junctions of normal mammary ducts and lobules, and of tubular and micropapillary structures within G1 and G2 ductal carcinomas. At these junctions, the localization of PLEKHA7 was along the circumferential belt (zonula adhaerens), and only partially overlapping with that of E-cadherin, p120ctn and ZO-1, as shown previously in rodent tissues. PLEKHA7 immunolabeling was strongly decreased in G3 ductal carcinomas and undetectable in lobular carcinomas. PLEKHA7 mRNA was detected in both ductal and lobular carcinomas, with no observed correlation between mRNA levels and tumor type or grade. In summary, PLEKHA7 is a junctional marker of epithelial cells within tubular structures both in normal breast tissue and ductal carcinomas, and since PLEKHA7 protein but not mRNA expression is strongly decreased or lost in high grade ductal carcinomas and in lobular carcinomas, loss of PLEKHA7 is a newly characterized feature of these carcinomas. PMID:26270346

  6. Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis.

    PubMed

    Shen, Dejun; Nooraie, Farzad; Elshimali, Yahya; Lonsberry, Victor; He, Jianbo; Bose, Shikha; Chia, David; Seligson, David; Chang, Helena R; Goodglick, Lee

    2006-12-01

    Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and a known mediator of glucocorticoid-regulated inflammatory responses. Using a combined multiple high-throughput approach, we recently identified a reduced expression of ANXA1 in human breast cancer. The finding was confirmed at the gene level by quantitative reverse transcription-polymerase chain reaction and at the protein level by immunohistochemical staining of normal, benign, and malignant breast tissues. In this study, we constructed and used a high-density human breast cancer tissue microarray to characterize the expressional pattern of ANXA1 according to histopathologies. The tissue microarray contains 1,158 informative breast tissue cores of different histologies including normal tissues, hyperplasia, in situ and invasive tumors, and lymph node metastases. Our results showed that there was a significant decrease in glandular expression of ANXA1 in ductal carcinoma in situ and invasive ductal carcinoma compared with either normal breast tissue or hyperplasia (P < .0001). Moreover, in benign breast tissue, myoepithelial cells showed strong expression of ANXA1. There was a decrease of ANXA1 expression in myoepithelial cells in ductal carcinoma in situ lesions compared with the same cell population in either normal or hyperplastic lesions. These results suggest that suppressed ANXA1 expression in breast tissue is correlated with breast cancer development and progression.

  7. Vitamin D compounds reduce mammosphere formation and decrease expression of putative stem cell markers in breast cancer.

    PubMed

    Wahler, Joseph; So, Jae Young; Cheng, Larry C; Maehr, Hubert; Uskokovic, Milan; Suh, Nanjoo

    2015-04-01

    Breast cancer stem cells (BCSCs) are a subset of tumor cells that are believed to be the cells responsible for the establishment and maintenance of tumors. Moreover, BCSCs are suggested to be the main cause of progression to metastasis and recurrence of cancer because of their tumor-initiating abilities and resistance to conventional therapies. Ductal carcinoma in situ (DCIS) is an early precursor in breast carcinogenesis which progresses to invasive ductal carcinoma (IDC). We have previously reported that a vitamin D compound, BXL0124, inhibits the progression of DCIS to IDC. In the present study we sought to determine whether this effect was mediated through an influence on BCSCs. In MCF10DCIS cells treated with vitamin D compounds (1α25(OH)2D3 or BXL0124), the breast cancer stem cell-like population, identified by the CD44(+)/CD24(-/low) and CD49f(+)/CD24(-/low) subpopulations, was reduced. To determine the effects of vitamin D compounds on cancer stem cell activity, the MCF10DCIS mammosphere cell culture system, which enriches for mammary progenitor cells and putative BCSCs, was utilized. Untreated MCF10DCIS mammospheres showed a disorganized and irregular shape. When MCF10DCIS cells were treated with 1α25(OH)2D3 or BXL0124, the mammospheres that formed exhibited a more organized, symmetrical and circular shape, similar to the appearance of spheres formed by the non-malignant, normal mammary epithelial cell line, MCF10A. The mammosphere forming efficiency (MFE) was significantly decreased upon treatment with 1α25(OH)2D3 or BXL0124, indicating that these compounds have an inhibitory effect on mammosphere development. Treatment with 1α25(OH)2D3 or BXL0124 repressed markers associated with the stem cell-like phenotype, such as CD44, CD49f, c-Notch1, and pNFκB. Furthermore, 1α25(OH)2D3 and BXL0124 reduced the expression of pluripotency markers, OCT4 and KLF-4 in mammospheres. This study suggests that vitamin D compounds repress the breast cancer stem cell

  8. Ixeris dentata (Thunb. Ex Thunb.) Nakai Extract Inhibits Proliferation and Induces Apoptosis in Breast Cancer Cells through Akt/NF-κB Pathways

    PubMed Central

    Shin, Seong-Ah; Lee, Hae-Nim; Choo, Gang-Sik; Kim, Hyeong-Jin; Che, Jeong-Hwan; Jung, Ji-Youn

    2017-01-01

    Ixeris dentata (Thunb. Ex Thunb.) Nakai (ID) exhibits various physiological activities, and its related plant derived-products are expected to represent promising cancer therapeutic agents. However, the anticancer effects of ID extract on breast cancer cells classified as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are still unknown. In this study, we investigated the anti-cancer effects and analyzed the molecular mechanism of ID extract in T47D, MCF-7 (ER-, PR-positive, HER2-negative), SK-BR-3(ER-, PR-negative, HER2-positive), and MDA-MB-231 (Triple-negative) through in vitro studies. Additionally, we examined its anti-tumor effects through in vivo studies. Our findings indicated that ID extract-induced apoptosis was mediated via various survival pathways on four breast cancer cells by identifying the factors including Bcl-2 family, phospho-Akt and phospho-nuclear factor-κB (NF-κB). Based on in vitro findings that induced apoptosis via Akt-NF-κB signaling, we investigated the effects of ID extract on mice bearing MDA-MB-231 cells. The results showed that ID extract significantly decreased MDA-MB-231 tumor volume and weight via inducing apoptosis by suppressing phospho-Akt. Overall, these results indicate that ID extract induces apoptosis through the Akt-NF-κB signaling pathway in MDA-MB-231 breast cancer cells and tumors, and it may serve as a therapeutic agent for triple-negative human breast cancer. PMID:28134814

  9. Anticancer activity of litchi fruit pericarp extract against human breast cancer in vitro and in vivo

    SciTech Connect

    Wang Xiujie . E-mail: xiujiewang@yahoo.com; Yuan Shulan; Wang Jing; Lin Ping; Liu Guanjian; Lu Yanrong; Zhang Jie; Wang, Wendong; Wei Yuquan . E-mail: yuquanwei@mail.sc.cninfo.net

    2006-09-01

    Litchi fruit pericarp (LFP) extract contains significant amounts of polyphenolic compounds and exhibits powerful antioxidative activity against fat oxidation in vitro. The purpose of this study is to confirm the anticancer activity of LFP extract on human breast cancer in vitro and in vivo, and to elucidate the mechanism of its activity. Human breast cancer cells were tested in vitro for cytotoxicity, colony formation inhibition, BrdU incorporation, and gene expression profiling after treatment with LFP extract. Seven nude mice bearing human breast infiltrating duct carcinoma orthotopically were tested for its anticancer activity and expression of caspase-3 in vivo by oral administration of 0.3% (0.3 mg/ml) of LFP water-soluble crude ethanolic extract (CEE) for 10 weeks. LFP extract demonstrated a dose- and time-dependent inhibitory effect on cell growth (IC{sub 5} = 80 {mu}g/ml), and it significantly inhibited colony formation and BrdU incorporation of human breast cancer cells. Oligonucleotide microarray analysis identified 41(1.22%) up-regulated and 129 (3.84%) down-regulated genes after LFP water-soluble CEE treatment; the predominantly up-regulated genes were involved in various biological functions including cell cycle regulation and cell proliferation, apoptosis, signal transduction and transcriptional regulation, and extracellular matrix/adhesion molecules; and down-regulated genes were mainly associated with adhesion, invasion, and malignancy of cancer cells. A 40.70% tumor mass volume reduction and significant increase of casepase-3 protein expression were observed in vivo experiment. The findings in this study suggested that LFP extract might have potential anticancer activity on both ER positive and negative breast cancers, which could be attributed, in part, to its DNA damage effect, proliferating inhibition and apoptosis induction of cancer cells through up-regulation and down-regulation of multiple genes involved in cell cycle regulation and cell

  10. Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells

    PubMed Central

    Liu, Jing; He, Chengwei; Zhou, Keyuan; Wang, Jingdong; Kang, Jing X.

    2008-01-01

    Estrogen receptor (ER) antagonists have been widely used for breast cancer treatment, but the efficacy and drug resistance remain to be clinical concerns. The purpose of this study was to determine whether the extracts of coptis, an anti-inflammatory herb, improve the anticancer efficacy of ER antagonists. The results showed that the combined treatment of ER antagonists and the crude extract of coptis or its purified compound berberine conferred synergistic growth inhibitory effect on MCF-7 cells (ER+), but not on MDA-MB-231 cells (ER-). The similar results were observed in the combined treatment of fulvestrant, a specific aromatase antagonist. Analysis of the expression of breast cancer related genes indicated that EGFR, HER2, bcl-2 and COX-2 were significantly downregulated, while IFN-β and p21 were remarkably upregulated by berberine. Our results suggest that coptis extracts could be promising adjuvant to ER antagonists in ER positive breast cancer treatment through regulating expression of multiple genes. PMID:19000652

  11. Inhibitory effects of herbal extracts on breast cancer resistance protein (BCRP) and structure-inhibitory potency relationship of isoflavonoids.

    PubMed

    Tamaki, Hirofumi; Satoh, Hiroki; Hori, Satoko; Ohtani, Hisakazu; Sawada, Yasufumi

    2010-01-01

    The inhibition of intestinal breast cancer resistance protein (BCRP), which restricts the absorption of xenobiotics, may increase the systemic availability of its substrates. The aim of this study was to evaluate the inhibitory effects of herbal extracts and their constituents on BCRP-mediated transport. The inhibitory effects of 9 herbal extracts and 23 isoflavonoids, including soybean-derived isoflavones, on BCRP-mediated methotrexate (MTX) transport were evaluated using BCRP-expressing membrane vesicles. The structure-inhibitory potency relationship was investigated by multiple factor analysis. Extracts of soybean, Gymnema sylvestre, black cohosh and passion flower and rutin strongly inhibited BCRP-mediated transport of MTX at 1 mg/ml, while inhibition by chlorella, milk thistle and Siberian ginseng extracts was weak. Among the 23 isoflavonoids examined, all of which inhibited BCRP-mediated transport, coumestrol showed the most potent inhibition (IC(50)=63 nM). The inhibitory potencies of 6 isoflavonoid glucosides were 10- to 100-fold lower than those of the corresponding aglycones. The addition of a 5-hydroxyl or 6-methoxyl moiety tended to potentiate the inhibition. The inhibitory potency of daidzein was decreased 100-fold by 7-glucuronidation, but was virtually unaffected by 4'-sulfation. Thus, some herbal and dietary supplements and isoflavonoids may increase the systemic availability of BCRP substrates when concomitantly given orally.

  12. Hydroxytyrosol rich extract from olive leaves modulates cell cycle progression in MCF-7 human breast cancer cells.

    PubMed

    Bouallagui, Zouhaier; Han, Junkuy; Isoda, Hiroko; Sayadi, Sami

    2011-01-01

    Throughout the history, olive (Olea europea L.) leaves have been heavily exploited for the prevention or the treatment of hypertension, carcinogenesis, diabetes, atherosclerosis and so many other traditional therapeutic uses. These activities are thought to be the output of olive micronutrients especially polyphenols. Hydroxytyrosol and oleuropein are considered as major polyphenolic compounds in olive leaf. In this work, a hydroxytyrosol rich olive leaves extract was investigated for potential anti-tumoral activities. In vitro cytotoxic effects against MCF-7 breast cancer cells were examined using MTT and neutral red tests. The anti-tumor activities were further investigated by flow cytometry and western blotting. Cytotoxicity assays resulted in a dose dependent growth inhibition of MCF-7 cells. This inhibition was due to the cell cycle arrest in the G0/G1 phase. The understanding of the molecular mechanism by which olive leaves extract arrested cell growth showed a down-expression of the peptidyl-prolyl cis-trans isomerase Pin1 which in turn decreased the level of a G1 key protein; Cyclin D1. Additionally, olive leaves extract treatment up-regulated the AP1 transcription factor member, c-jun. Therefore, olive leaves extract will necessitate further deep investigation for a probable use as a cancer preventive food additive.

  13. Radiation for Hodgkin's Lymphoma in Young Female Patients: A New Technique to Avoid the Breasts and Decrease the Dose to the Heart

    SciTech Connect

    Dabaja, Bouthaina S.; Rebueno, Neal C.S.; Mazloom, Ali; Thorne, Scott; Perrin, Kelly J.; Tolani, Naresh; Das, Pragnan; Delclos, Marc E.; Iyengar, Puneeth; Reed, Valerie K.; Horace, Patrecia; Salehpour, Mohammad R.

    2011-02-01

    Purpose: To demonstrate how, in young female patients with Hodgkin's lymphoma, using an inclined board technique can further decrease the volume of breasts and heart in the treatment field. Methods and Materials: An inclined board was constructed with the ability to mount an Aquaplast face mask, a Vacu-Lock, and a hip stopper. Eight female patients with early-stage Hodgkin's lymphoma were planned and compared using the conventional flat position and the inclined board position. All patients on the inclined board were planned with 90{sup o} degree table position and 15{sup o} gantry angle rotation to compensate for the beam divergence resulting from the patient's position on the inclined board. Dose-volume histograms were generated, as well as the mean V30 and V5 of both breasts and heart using both treatment positions. Results: The mean value of V30 of the right breast, left breast, and heart decreased from 3%, 3%, and 13%, respectively, using the flat position to 0, 0.4%, and 5%, respectively, using the inclined board. The mean value of V5 of the right breast, left breast, and heart decreased from 6%, 13%, and 36%, respectively, using the flat position to 2%, 8%, and 29%, respectively, using the inclined board. Conclusions: Compared with conventional flat positioning, this simple device and technique allows better sparing of the breasts and the heart while maintaining comparable target coverage and total lung dose.

  14. Radiation for Hodgkin's lymphoma in young female patients: a new technique to avoid the breasts and decrease the dose to the heart.

    PubMed

    Dabaja, Bouthaina S; Rebueno, Neal C S; Mazloom, Ali; Thorne, Scott; Perrin, Kelly J; Tolani, Naresh; Das, Pragnan; Delclos, Marc E; Iyengar, Puneeth; Reed, Valerie K; Horace, Patrecia; Salehpour, Mohammad R

    2011-02-01

    To demonstrate how, in young female patients with Hodgkin's lymphoma, using an inclined board technique can further decrease the volume of breasts and heart in the treatment field. An inclined board was constructed with the ability to mount an Aquaplast face mask, a Vacu-Lock, and a hip stopper. Eight female patients with early-stage Hodgkin's lymphoma were planned and compared using the conventional flat position and the inclined board position. All patients on the inclined board were planned with 90° degree table position and 15° gantry angle rotation to compensate for the beam divergence resulting from the patient's position on the inclined board. Dose-volume histograms were generated, as well as the mean V30 and V5 of both breasts and heart using both treatment positions. The mean value of V30 of the right breast, left breast, and heart decreased from 3%, 3%, and 13%, respectively, using the flat position to 0, 0.4%, and 5%, respectively, using the inclined board. The mean value of V5 of the right breast, left breast, and heart decreased from 6%, 13%, and 36%, respectively, using the flat position to 2%, 8%, and 29%, respectively, using the inclined board. Compared with conventional flat positioning, this simple device and technique allows better sparing of the breasts and the heart while maintaining comparable target coverage and total lung dose. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Anti-Inflammatory Effects of a Methanol Extract from the Marine Sponge Geodia cydonium on the Human Breast Cancer MCF-7 Cell Line

    PubMed Central

    Costantini, Susan; Romano, Giovanna; Rusolo, Fabiola; Capone, Francesca; Guerriero, Eliana; Ianora, Adrianna

    2015-01-01

    Many research groups are working to find new possible anti-inflammatory molecules, and marine sponges represent a rich source of biologically active compounds with pharmacological applications. In the present study, we tested different concentrations of the methanol extract from the marine sponge, Geodia cydonium, on normal human breast epithelial cells (MCF-10A) and human breast cancer cells (MCF-7). Our results show that this extract has no cytotoxic effects on both cell lines whereas it induces a decrease in levels of VEGF and five proinflammatory cytokines (CCL2, CXCL8, CXCL10, IFN-γ, and TNF-α) only in MCF-7 cells in a dose-dependent manner, thereby indicating an anti-inflammatory effect. Moreover, interactomic analysis suggests that all six cytokines are involved in a network and are connected with some HUB nodes such as NF-kB subunits and ESR1 (estrogen receptor 1). We also report a decrease in the expression of two NFKB1 and c-Rel subunits by RT-qPCR experiments only in MCF-7 cells after extract treatment, confirming NF-kB inactivation. These data highlight the potential of G. cydonium for future drug discovery against major diseases, such as breast cancer. PMID:26491222

  16. Green tea extract decreases muscle pathology and NF-κB immunostaining in regenerating muscle fibers of mdx mice

    PubMed Central

    Evans, Nicholas P.; Call, Jarrod A.; Bassaganya-Riera, Josep; Robertson, John L.; Grange, Robert W.

    2009-01-01

    BACKGROUND & AIMS Duchenne muscular dystrophy is a debilitating genetic disorder characterized by severe muscle wasting and early death in afflicted boys. The primary cause of this disease is mutations in the dystrophin gene resulting in massive muscle degeneration and inflammation. The purpose of this study was to determine if dystrophic muscle pathology and inflammation were decreased by pre-natal and early dietary intervention with green tea extract. METHODS Mdx breeder mice and pups were fed diets containing 0.25% or 0.5% green tea extract and compared to untreated mdx and C57BL/6J mice. Serum creatine kinase was assessed as a systemic indicator of muscle damage. Quantitative histopathological and immunohistochemical techniques were used to determine muscle pathology, macrophage infiltration, and NF-κB localization. RESULTS Early treatment of mdx mice with green tea extract significantly decreased serum creatine kinase by ~85% at age 42 days (P≤0.05). In these mice, the area of normal fiber morphology was increased by as much as ~32% (P≤0.05). The primary histopathological change was a ~21% decrease in the area of regenerating fibers (P≤0.05). NF-κB staining in regenerating muscle fibers was also significantly decreased in green tea extract-treated mdx mice when compared to untreated mdx mice. CONCLUSION Early treatment with green tea extract decreases dystrophic muscle pathology potentially by regulating NF-κB activity in regenerating muscle fibers. PMID:19897286

  17. Effects of Urtica dioica dichloromethane extract on cell apoptosis and related gene expression in human breast cancer cell line (MDA-MB-468).

    PubMed

    Mohammadi, A; Mansoori, B; Goldar, S; Shanehbandi, D; Khaze, V; Mohammadnejad, L; Baghbani, E; Baradaran, B

    2016-02-29

    Breast cancer is the most common cancer among women in worldwide, especially in developing countries. Therefore, a large number of anticancer agents with herbal origins have been reported against this deadly disease. This study is the first to examine the cytotoxic and apoptotic effects of Urtica dioica in MDA-MB-468, human breast adenocarcinoma cells. The 3-(4,5-dimethylethiazol-2 yl)-2,5- diphenyltetrazolium (MTT) reduction and trypan-blue exclusion assay were performed in MDA-MB-468 cells as well as control cell line L929 to analyze the cytotoxic activity of the dichloromethane extract. In addition, Apoptosis induction of Urtica dioica on the MDA-MB-468 cells was assessed using TUNEL (terminal deoxy transferase (TdT)-mediated dUTP nick- end labeling) assay and DNA fragmentation analysis and real-time polymerase chain reaction (PCR). The results showed that the extract significantly inhibited cell growth and viability without inducing damage to normal control cells. Nuclei Staining in TUNEL and DNA fragments in DNA fragmentation assay and increase in the mRNA expression levels of caspase-3, caspase-9, decrease in the bcl2 and no significant change in the caspase-8 mRNA expression level, showed that the induction of apoptosis was the main mechanism of cell death that induce by Urtica dioica extract. Our results suggest that urtica dioica dichloromethane extract may contain potential bioactive compound(s) for the treatment of breast adenocarcinoma.

  18. Cytotoxic Activities against Breast Cancer Cells of Local Justicia gendarussa Crude Extracts

    PubMed Central

    Abd Samad, Azman; Jamil, Shajarahtunnur

    2014-01-01

    Justicia gendarussa methanolic leaf extracts from five different locations in the Southern region of Peninsular Malaysia and two flavonoids, kaempferol and naringenin, were tested for cytotoxic activity. Kaempferol and naringenin were two flavonoids detected in leaf extracts using gas chromatography-flame ionization detection (GC-FID). The results indicated that highest concentrations of kaempferol and naringenin were detected in leaves extracted from Mersing with 1591.80 mg/kg and 444.35 mg/kg, respectively. Positive correlations were observed between kaempferol and naringenin concentrations in all leaf extracts analysed with the Pearson method. The effects of kaempferol and naringenin from leaf extracts were examined on breast cancer cell lines (MDA-MB-231 and MDA-MB-468) using MTT assay. Leaf extract from Mersing showed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 40 μg/mL, respectively, compared to other leaf extracts. Kaempferol possessed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 34 μg/mL, respectively. These findings suggest that the presence of kaempferol in Mersing leaf extract contributed to high cytotoxicity of both MDA-MB-231 and MDA-MB-468 cancer cell lines. PMID:25574182

  19. Cytotoxic Activities against Breast Cancer Cells of Local Justicia gendarussa Crude Extracts.

    PubMed

    Ayob, Zahidah; Mohd Bohari, Siti Pauliena; Abd Samad, Azman; Jamil, Shajarahtunnur

    2014-01-01

    Justicia gendarussa methanolic leaf extracts from five different locations in the Southern region of Peninsular Malaysia and two flavonoids, kaempferol and naringenin, were tested for cytotoxic activity. Kaempferol and naringenin were two flavonoids detected in leaf extracts using gas chromatography-flame ionization detection (GC-FID). The results indicated that highest concentrations of kaempferol and naringenin were detected in leaves extracted from Mersing with 1591.80 mg/kg and 444.35 mg/kg, respectively. Positive correlations were observed between kaempferol and naringenin concentrations in all leaf extracts analysed with the Pearson method. The effects of kaempferol and naringenin from leaf extracts were examined on breast cancer cell lines (MDA-MB-231 and MDA-MB-468) using MTT assay. Leaf extract from Mersing showed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 40 μg/mL, respectively, compared to other leaf extracts. Kaempferol possessed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 34 μg/mL, respectively. These findings suggest that the presence of kaempferol in Mersing leaf extract contributed to high cytotoxicity of both MDA-MB-231 and MDA-MB-468 cancer cell lines.

  20. Computational approach to radiogenomics of breast cancer: Luminal A and luminal B molecular subtypes are associated with imaging features on routine breast MRI extracted using computer vision algorithms.

    PubMed

    Grimm, Lars J; Zhang, Jing; Mazurowski, Maciej A

    2015-10-01

    To identify associations between semiautomatically extracted MRI features and breast cancer molecular subtypes. We analyzed routine clinical pre-operative breast MRIs from 275 breast cancer patients at a single institution in this retrospective, Institutional Review Board-approved study. Six fellowship-trained breast imagers reviewed the MRIs and annotated the cancers. Computer vision algorithms were then used to extract 56 imaging features from the cancers including morphologic, texture, and dynamic features. Surrogate markers (estrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor-2 [HER2]) were used to categorize tumors by molecular subtype: ER/PR+, HER2- (luminal A); ER/PR+, HER2+ (luminal B); ER/PR-, HER2+ (HER2); ER/PR/HER2- (basal). A multivariate analysis was used to determine associations between the imaging features and molecular subtype. The imaging features were associated with both luminal A (P = 0.0007) and luminal B (P = 0.0063) molecular subtypes. No association was found for either HER2 (P = 0.2465) or basal (P = 0.1014) molecular subtype and the imaging features. A P-value of 0.0125 (0.05/4) was considered significant. Luminal A and luminal B molecular subtype breast cancer are associated with semiautomatically extracted features from routine contrast enhanced breast MRI. © 2015 Wiley Periodicals, Inc.

  1. Decreased DNA repair gene XRCC1 expression is associated with radiotherapy-induced acute side effects in breast cancer patients.

    PubMed

    Batar, Bahadir; Guven, Gulgun; Eroz, Seda; Bese, Nuran Senel; Guven, Mehmet

    2016-05-10

    DNA repair plays a critical role in response to ionizing radiation (IR) and developing of radiotherapy induced normal tissue reactions. In our study, we investigated the association of radiotherapy related acute side effects, with X-ray repair cross complementing group 1 (XRCC1) and Poly (ADP-ribose) polymerase 1 (PARP1) DNA repair gene expression levels, their changes in protein expression and DNA damage levels in breast cancer patients. The study included 40 women with newly diagnosed breast cancer; an experimental case group (n=20) with acute side effects and the control group (n=20) without side effects. For gene and protein expression analysis, lymphocytes were cultured for 72 h and followed by in vitro 2 Gray (Gy) gamma-irradiation. For detection of DNA damage levels, lymphocytes were irradiated with in vitro 2 Gy gamma-rays and followed by incubation for 72 h. XRCC1 mRNA and protein expression levels were significantly higher in controls than in experimental cases (P=0.020). In terms of DNA damage levels, an increased frequency of micronucleus (MN) was observed in experimental cases versus controls, but this association was not significant (P=0.206). We also observed a significant negative correlation between MN frequency and XRCC1 protein levels in experimental (r=-0.469, P=0.037) vs control (r=-0.734, P<0.001). Our results suggested that decreased XRCC1 expression levels might be associated with the increased risk of therapeutic IR-related acute side effects in patients with breast cancer.

  2. Urtica dioica Extract Inhibits Proliferation and Induces Apoptosis and Related Gene Expression of Breast Cancer Cells In Vitro and In Vivo.

    PubMed

    Mohammadi, Ali; Mansoori, Behzad; Baradaran, Pooneh Chokhachi; Khaze, Vahid; Aghapour, Mahyar; Farhadi, Mehrdad; Baradaran, Behzad

    2017-04-21

    Currently, because the prevalence of breast cancer and its consequent mortality has increased enormously in the female population, a number of studies have been designed to identify natural products with special antitumor properties. The main purpose of the present study was to determine the effect of Urtica dioica on triggering apoptosis and diminishing growth, size, and weight of the tumor in an allograft model of BALB/c mice. In the present study, a BALB/c mouse model of breast cancer (4T1) was used. After emergence of tumor, 2 groups of mice received the extract, 1 group at a dose of 10 mg/kg and 1 group at a dose of 20 mg/kg, by intraperitoneal injection for 28 days. During the test and after removal of the tumor mass, the size and weight of the tumor were measured. To assess the induction of apoptosis in the cancer cells, the TUNEL (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling) assay was performed. The Ki-67 test was used to evaluate tumor proliferation. The results showed that the tumor size in the mice treated with the extract decreased significantly. The weight of the tumor mass in the treated mice after resection was less than that in the control group. The TUNEL assay findings revealed that apoptosis occurred in the treated group. The Ki-67 test findings also demonstrated that administration of the extract suppressed the growth of tumor cells. These results suggest that U. dioica extract can decrease the growth of breast tumors and induce apoptosis in tumor cells; thus, it might represent an ideal therapeutic tool for breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Different extracts of Zingiber officinale decrease Enterococcus faecalis infection in Galleria mellonella.

    PubMed

    Maekawa, Lilian Eiko; Rossoni, Rodnei Dennis; Barbosa, Júnia Oliveira; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos; Valera, Marcia Carneiro

    2015-01-01

    Dried, fresh and glycolic extracts of Zingiber officinale were obtained to evaluate the action against G. mellonella survival assay against Enterococcus faecalis infection. Eighty larvae were divided into: 1) E. faecalis suspension (control); 2) E. faecalis + fresh extract of Z. officinale (FEO); 3) E. faecalis + dried extract of Z. officinale (DEO); 4) E. faecalis + glycolic extract of Z. officinale (GEO); 5) Phosphate buffered saline (PBS). For control group, a 5 μL inoculum of standardized suspension (107 cells/mL) of E. faecalis (ATCC 29212) was injected into the last left proleg of each larva. For the treatment groups, after E. faecalis inoculation, the extracts were also injected, but into the last right proleg. The larvae were stored at 37 °C and the number of dead larvae was recorded daily for 168 h (7 days) to analyze the survival curve. The larvae were considered dead when they did not show any movement after touching. E. faecalis infection led to the death of 85% of the larvae after 168 h. Notwithstanding, in treatment groups with association of extracts, there was an increase in the survival rates of 50% (GEO), 61% (FEO) and 66% (DEO) of the larvae. In all treatment groups, the larvae exhibited a survival increase with statistically significant difference in relation to control group (p=0.0029). There were no statistically significant differences among treatment groups with different extracts (p=0.3859). It may be concluded that the tested extracts showed antimicrobial activity against E. faecalis infection by increasing the survival of Galleria mellonella larvae.

  4. Influence of polyphenol extract from evening primrose (Oenothera paradoxa) seeds on human prostate and breast cancer cell lines.

    PubMed

    Lewandowska, Urszula; Owczarek, Katarzyna; Szewczyk, Karolina; Podsędek, Anna; Koziołkiewicz, Maria; Hrabec, Elżbieta

    2014-02-03

    There is growing interest in plant polyphenols which exhibit pleiotropic biological activities, including anti-inflammatory, antioxidant, and anticancer effects. The objective of our study was to evaluate the influence of an evening primrose extract (EPE) from defatted seeds on viability and invasiveness of three human cell lines: PNT1A (normal prostate cells), DU145 (prostate cancer cells) and MDA-MB-231 (breast cancer cells). The results revealed that after 72 h of incubation the tested extract reduced the viability of DU 145 and MDA-MB-231 with IC50 equal to 14.5 μg/mL for both cell lines. In contrast, EPE did not inhibit the viability of normal prostate cells. Furthermore, EPE reduced PNT1A and MDA-MB-231 cell invasiveness; at the concentration of 21.75 μg/mL the suppression of invasion reached 92% and 47%, respectively (versus control). Additionally, zymographic analysis revealed that after 48 h of incubation EPE inhibited metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) activities in a dose-dependent manner. For PNT1A the activities of MMP-2 and MMP-9 decreased 4- and 2-fold, respectively, at EPE concentration of 29 μg/mL. In the case of MDA-MB-231 and DU 145 the decrease in MMP-9 activity at EPE concentration of 29 μg/mL was 5.5-fold and almost 1.9-fold, respectively. In conclusion, this study suggests that EPE may exhibit antimigratory, anti-invasive and antimetastatic potential towards prostate and breast cancer cell lines.

  5. Inhibition of PRL-2·CNNM3 Protein Complex Formation Decreases Breast Cancer Proliferation and Tumor Growth.

    PubMed

    Kostantin, Elie; Hardy, Serge; Valinsky, William C; Kompatscher, Andreas; de Baaij, Jeroen H F; Zolotarov, Yevgen; Landry, Melissa; Uetani, Noriko; Martínez-Cruz, Luis Alfonso; Hoenderop, Joost G J; Shrier, Alvin; Tremblay, Michel L

    2016-05-13

    The oncogenic phosphatase of regenerating liver 2 (PRL-2) has been shown to regulate intracellular magnesium levels by forming a complex through an extended amino acid loop present in the Bateman module of the CNNM3 magnesium transporter. Here we identified highly conserved residues located on this amino acid loop critical for the binding with PRL-2. A single point mutation (D426A) of one of those critical amino acids was found to completely disrupt PRL-2·human Cyclin M 3 (CNNM3) complex formation. Whole-cell voltage clamping revealed that expression of CNNM3 influenced the surface current, whereas overexpression of the binding mutant had no effect, indicating that the binding of PRL-2 to CNNM3 is important for the activity of the complex. Interestingly, overexpression of the CNNM3 D426A-binding mutant in cancer cells decreased their ability to proliferate under magnesium-deprived situations and under anchorage-independent growth conditions, demonstrating a PRL-2·CNNM3 complex-dependent oncogenic advantage in a more stringent environment. We further confirmed the importance of this complex in vivo using an orthotopic xenograft breast cancer model. Finally, because molecular modeling showed that the Asp-426 side chain in CNNM3 buries into the catalytic cavity of PRL-2, we showed that a PRL inhibitor could abrogate complex formation, resulting in a decrease in proliferation of human breast cancer cells. In summary, we provide evidence that this fundamental regulatory aspect of PRL-2 in cancer cells could potentially lead to broadly applicable and innovative therapeutic avenues.

  6. A new breast cancer risk analysis approach using features extracted from multiple sub-regions on bilateral mammograms

    NASA Astrophysics Data System (ADS)

    Sun, Wenqing; Tseng, Tzu-Liang B.; Zheng, Bin; Zhang, Jianying; Qian, Wei

    2015-03-01

    A novel breast cancer risk analysis approach is proposed for enhancing performance of computerized breast cancer risk analysis using bilateral mammograms. Based on the intensity of breast area, five different sub-regions were acquired from one mammogram, and bilateral features were extracted from every sub-region. Our dataset includes 180 bilateral mammograms from 180 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including sub-region segmentation, bilateral feature extraction, feature selection, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under the curve (AUC) is 0.763 ± 0.021 when applying the multiple sub-region features to our testing dataset. The positive predictive value and the negative predictive value were 0.60 and 0.73, respectively. The study demonstrates that (1) features extracted from multiple sub-regions can improve the performance of our scheme compared to using features from whole breast area only; (2) a classifier using asymmetry bilateral features can effectively predict breast cancer risk; (3) incorporating texture and morphological features with density features can boost the classification accuracy.

  7. Rosemary (Rosmarinus officinalis) extract modulates CHOP/GADD153 to promote androgen receptor degradation and decreases xenograft tumor growth.

    PubMed

    Petiwala, Sakina M; Berhe, Saba; Li, Gongbo; Puthenveetil, Angela G; Rahman, Ozair; Nonn, Larisa; Johnson, Jeremy J

    2014-01-01

    The Mediterranean diet has long been attributed to preventing or delaying the onset of cardiovascular disease, diabetes and various solid organ cancers. In this particular study, a rosemary extract standardized to carnosic acid was evaluated for its potential in disrupting the endoplasmic reticulum machinery to decrease the viability of prostate cancer cells and promote degradation of the androgen receptor. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two different patients undergoing radical prostatectomy were treated with standardized rosemary extract and evaluated by flow cytometry, MTT, BrdU, Western blot and fluorescent microscopy. A significant modulation of endoplasmic reticulum stress proteins was observed in cancer cells while normal prostate epithelial cells did not undergo endoplasmic reticulum stress. This biphasic response suggests that standardized rosemary extract may preferentially target cancer cells as opposed to "normal" cells. Furthermore, we observed standardized rosemary extract to decrease androgen receptor expression that appears to be regulated by the expression of CHOP/GADD153. Using a xenograft tumor model we observed standardized rosemary extract when given orally to significantly suppress tumor growth by 46% compared to mice not receiving standardized rosemary extract. In the last several years regulatory governing bodies (e.g. European Union) have approved standardized rosemary extracts as food preservatives. These results are especially significant as it is becoming more likely that individuals will be receiving standardized rosemary extracts that are a part of a natural preservative system in various food preparations. Taken a step further, it is possible that the potential benefits that are often associated with a "Mediterranean Diet" in the future may begin to extend beyond the Mediterranean diet as more of the population is consuming standardized rosemary extracts.

  8. Momordica cochinchinensis Aril Extract Induced Apoptosis in Human MCF-7 Breast Cancer Cells.

    PubMed

    Petchsak, Phuchong; Sripanidkulchai, Bungorn

    2015-01-01

    Momordica cochinchinensis Spreng (MC) has been used in traditional medicine due to its high carotenoid content. The objective of this study was to investigate mechanisms underlying apoptotic effects of MC on human MCF-7 breast cancer cells. A lycopene-enriched aril extract of MC (AE) showed cytotoxicity and antiestrogenicity to MCF-7 cells. On DAPI staining, AE induced cell shrinkage and chromatin condensation were evident. With flow cytometric analysis, AE increased the percentage of cells in an early apoptosis stage when compared with the control group. RT-PCR analysis showed AE to significantly increase the expression of the proapoptotic bax gene without effect on expression of the anti-apoptotic bcl-2 gene. Moreover, AE enhanced caspase 6, 8 and 9 activity. Taken together, we conclude that AE of MC fruit has anticancer effects on human MCF-7 breast cancer cells by induction of cell apoptosis via both intrinsic and extrinsic pathways of signaling.

  9. Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells.

    PubMed

    Sahpazidou, Despina; Geromichalos, George D; Stagos, Dimitrios; Apostolou, Anna; Haroutounian, Serkos A; Tsatsakis, Aristidis M; Tzanakakis, George N; Hayes, A Wallace; Kouretas, Dimitrios

    2014-10-15

    A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods. Afterwards, the grape stem extracts were examined for their ability to inhibit growth of colon (HT29), breast (MCF-7 and MDA-MB-23), renal (786-0 and Caki-1) and thyroid (K1) cancer cells. The cancer cells were exposed to the extracts for 72 h and the effects on cell growth were evaluated using the SRB assay. The results indicated that all extracts inhibited cell proliferation, with IC₅₀ values of 121-230 μg/ml (MCF-7), 121-184 μg/ml (MDA-MD-23), 175-309 μg/ml (HT29), 159-314 μg/ml (K1), 180-225 μg/ml (786-0) and 134->400 μg/ml (Caki-1). This is the first study presenting the inhibitory activity of grape stem extracts against growth of colon, breast, renal and thyroid cancer cells. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Shotgun proteomic analysis to study the decrease of xenograft tumor growth after rosemary extract treatment.

    PubMed

    Valdés, Alberto; García-Cañas, Virginia; Pérez-Sánchez, Almudena; Barrajón-Catalán, Enrique; Ruiz-Torres, Verónica; Artemenko, Konstantin A; Micol, Vicente; Bergquist, Jonas; Cifuentes, Alejandro

    2017-05-26

    The antiproliferative activity of Rosemary (Rosmarinus officinalis) has been widely studied in different in vitro and in vivo models, which demonstrate that rosemary extracts inhibit the cellular proliferation due to its ability to interact with a wide spectrum of molecular targets. However, a comprehensive proteomics study in vivo has not been carried out yet. In the present work, the effects of rosemary extract on xenograft tumor growth has been studied and, for the first time, a shotgun proteomic analysis based on nano-LC-MS/MS together with stable isotope dimethyl labeling (DML) has been applied to investigate the global protein changes in vivo. Our results show that the daily administration of a polyphenol-enriched rosemary extract reduces the progression of colorectal cancer in vivo with the subsequent deregulation of 74 proteins. The bioinformatic analysis of these proteins indicates that the rosemary extract mainly alters the RNA Post-Transcriptional Modification, the Protein Synthesis and the Amino Acid Metabolism functions and suggests the inactivation of the oncogene MYC. These results demonstrate the high utility of the proposed analytical methodology to determine, simultaneously, the expression levels of a large number of protein biomarkers and to generate new hypothesis about the molecular mechanisms of this extract in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Aqueous Leaf Extract of Jatropha mollissima (Pohl) Bail Decreases Local Effects Induced by Bothropic Venom

    PubMed Central

    Gomes, Jacyra Antunes dos Santos; Geraldo Amaral, Juliano; Lopes, Norberto Peporine; Tabosa do Egito, Eryvaldo Sócrates; da Silva-Júnior, Arnóbio Antônio; Maria Zucolotto, Silvana

    2016-01-01

    Snakebites are a serious worldwide public health problem. In Brazil, about 90% of accidents are attributed to snakes from the Bothrops genus. The specific treatment consists of antivenom serum therapy, which has some limitations such as inability to neutralize local effects, difficult access in some regions, risk of immunological reactions, and high cost. Thus, the search for alternative therapies to treat snakebites is relevant. Jatropha mollissima (Euphorbiaceae) is a medicinal plant popularly used in folk medicine as an antiophidic remedy. Therefore, this study aims to evaluate the effect of the aqueous leaf extract from J. mollissima on local effects induced by Bothrops venoms. High Performance Liquid Chromatography with Diode Array Detection analysis and Mass Spectrometry analysis of aqueous leaf extract confirmed the presence of the flavonoids isoschaftoside, schaftoside, isoorientin, orientin, vitexin, and isovitexin. This extract, at 50–200 mg/kg doses administered by intraperitoneal route, showed significant inhibitory potential against local effects induced by Bothrops erythromelas and Bothrops jararaca snake venoms. Local skin hemorrhage, local edema, leukocyte migration, and myotoxicity were significantly inhibited by the extract. These results demonstrate that J. mollissima extract possesses inhibitory potential, especially against bothropic venoms, suggesting its potential as an adjuvant in treatment of snakebites. PMID:27847818

  12. Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3

    PubMed Central

    Ao, Xiang; Nie, Peipei; Wu, Baoyan; Xu, Wei; Zhang, Tao; Wang, Songmao; Chang, Haocai; Zou, Zhengzhi

    2016-01-01

    Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. In this study, nuclear receptor coactivator 3 (NCOA3) was found to be significantly increased in taxol-resistant breast cancer tissues and cells. Moreover, overexpression of NCOA3 enhanced breast cancer cell resistance to taxol, whereas depletion of NCOA3 decreased taxol resistance. Subsequently, we investigated whether NCOA3 expression was regulated by miRNAs in breast cancer. By bioinformatics prediction in combination with the data of previous report, miR-17 and miR-20b were selected as the potential miRNAs targeting NCOA3. By real-time PCR analysis, we found that miR-17 and miR-20b were significantly reduced in taxol-resistant breast cancer tissues and cells. In addition, we provided some experimental evidences that miR-17 and miR-20b attenuated breast cancer resistance to taxol in vitro and in vivo models. Furthermore, by luciferase reporter assays, we further validated that both miR-17 and miR-20b directly binded the 3′-untranslated region of NCOA3 mRNA and inhibited its expression in breast cancer cells. Finally, both miR-17 and miR-20b levels were found to be significantly negatively correlated with NCOA3 mRNA levels in breast cancer tissues. Together, our results indicated that loss of miR-17 and miR-20b enhanced breast cancer resistance to taxol by upregulating NCOA3 levels. Our study suggested miR-17, miR-20b and NCOA3 may serve as some predictive biomarkers and potential therapeutic targets in taxol-resistant breast cancer treatment. PMID:27831559

  13. Decreased expression of microRNA-17 and microRNA-20b promotes breast cancer resistance to taxol therapy by upregulation of NCOA3.

    PubMed

    Ao, Xiang; Nie, Peipei; Wu, Baoyan; Xu, Wei; Zhang, Tao; Wang, Songmao; Chang, Haocai; Zou, Zhengzhi

    2016-11-10

    Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. In this study, nuclear receptor coactivator 3 (NCOA3) was found to be significantly increased in taxol-resistant breast cancer tissues and cells. Moreover, overexpression of NCOA3 enhanced breast cancer cell resistance to taxol, whereas depletion of NCOA3 decreased taxol resistance. Subsequently, we investigated whether NCOA3 expression was regulated by miRNAs in breast cancer. By bioinformatics prediction in combination with the data of previous report, miR-17 and miR-20b were selected as the potential miRNAs targeting NCOA3. By real-time PCR analysis, we found that miR-17 and miR-20b were significantly reduced in taxol-resistant breast cancer tissues and cells. In addition, we provided some experimental evidences that miR-17 and miR-20b attenuated breast cancer resistance to taxol in vitro and in vivo models. Furthermore, by luciferase reporter assays, we further validated that both miR-17 and miR-20b directly binded the 3'-untranslated region of NCOA3 mRNA and inhibited its expression in breast cancer cells. Finally, both miR-17 and miR-20b levels were found to be significantly negatively correlated with NCOA3 mRNA levels in breast cancer tissues. Together, our results indicated that loss of miR-17 and miR-20b enhanced breast cancer resistance to taxol by upregulating NCOA3 levels. Our study suggested miR-17, miR-20b and NCOA3 may serve as some predictive biomarkers and potential therapeutic targets in taxol-resistant breast cancer treatment.

  14. The Influence of Chlorella and Its Hot Water Extract Supplementation on Quality of Life in Patients with Breast Cancer

    PubMed Central

    Noguchi, Naoto; Maruyama, Isao; Yamada, Akira

    2014-01-01

    A self-control, randomized, and open-label clinical trial was performed to test the effects of the unicellular green algae Chlorella and hot water extract supplementation on quality of life (QOL) in patients with breast cancer. Forty-five female patients with breast cancer who were living at home and not hospitalized were randomly assigned to 3 groups receiving vitamin mix tablet (control), Chlorella granules (test food-1), or Chlorella extract drink (test food-2) daily for one month. The Functional Assessment of Cancer Therapy-Breast (FACT-B), the Izumo scale for abdominal symptom-specific QOL, and a narrative-form questionnaire were used to determine outcomes. Data of thirty-six subjects were included for final analysis. FACT-B scores at presupplementation found no significant group differences in all subscales. Scores on the breast cancer subscale in the Chlorella granule group significantly increased during the supplementation period (P = 0.042). Fifty percent of the Chlorella extract group reported positive effects by the test food such as reduction of fatigue and improvements of dry skin (P < 0.01 versus control group). The findings suggested the beneficial effects of Chlorella on breast cancer-related QOL and of Chlorella extract on vitality status in breast cancer patients. These findings need to be confirmed in a larger study. PMID:24799942

  15. Green tea catechin extract in intervention of chronic breast cell carcinogenesis induced by environmental carcinogens.

    PubMed

    Rathore, Kusum; Wang, Hwa-Chain Robert

    2012-03-01

    Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically achievable concentration of 2.5 µg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.

  16. A new feature extraction framework based on wavelets for breast cancer diagnosis.

    PubMed

    Ergin, Semih; Kilinc, Onur

    2014-08-01

    This paper investigates a pattern recognition framework in order to determine and classify breast cancer cases. Initially, a two-class separation study classifying normal and abnormal (cancerous) breast tissues is achieved. The Histogram of Oriented Gradients (HOG), Dense Scale Invariant Feature Transform (DSIFT), and Local Configuration Pattern (LCP) methods are used to extract the rotation- and scale-invariant features for all tissue patches. A classification is made utilizing Support Vector Machine (SVM), k-Nearest Neighborhood (k-NN), Decision Tree, and Fisher Linear Discriminant Analysis (FLDA) via 10-fold cross validation. Then, a three-class study (normal, benign, and malignant cancerous cases) is carried out using similar procedures in a two-class case; however, the attained classification accuracies are not sufficiently satisfied. Therefore, a new feature extraction framework is proposed. The feature vectors are again extracted with this new framework, and more satisfactory results are obtained. Our new framework achieved a remarkable increase in recognition performance for the three-class study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Extraction of lignans from flaxseed and evaluation of their biological effects on breast cancer MCF-7 and MDA-MB-231 cell lines.

    PubMed

    Lehraiki, Abdelali; Attoumbré, Jacques; Bienaimé, Christophe; Matifat, Fabrice; Bensaddek, Lamine; Nava-Saucedo, Edmundo; Fliniaux, Marc-André; Ouadid-Ahidouch, Halima; Baltora-Rosset, Sylvie

    2010-08-01

    Over the last decade, there has been an increasing interest in using flaxseed (Linum usitatissimum) in diet in order to improve nutritional and health status. Lignans are major components of flaxseed. Therefore an extraction procedure for lignans from flaxseed has been optimized. The influence of some parameters was investigated: first the preliminary extraction step with alcoholic solvent, and then the solvent polarity and pH of the extract. All these conditions affected the total lignan content, but the most critical variables were preliminary extraction and solvent polarity. The optimized procedure, consisting of a direct hydrolysis in hydrochloric acid (1 M) at 100 degrees C for 1 hour followed by an extraction with a mixture of ethyl acetate/hexane (90:10 vol/vol), was applied to 340 g of defatted flaxseed and resulted in the isolation of secoisolariciresinol and anhydrosecoisolariciresinol with a purity of 97% and 98%, respectively, as determined by high-performance liquid chromatography. The ability of these two compounds and that of secoisolariciresinol diglucoside to modulate the growth of human breast cancer MCF-7 and MDA-MB-231 cell lines was assessed. Our results show that lignans modulate development of breast cancer cells. The most intense effect was observed for anhydrosecoisolariciresinol, which significantly decreased cell growth at 50 and 100 microM.

  18. Selectivity of Pinus sylvestris extract and essential oil to estrogen-insensitive breast cancer cells Pinus sylvestris against cancer cells

    PubMed Central

    Hoai, Nguyen Thi; Duc, Ho Viet; Thao, Do Thi; Orav, Anne; Raal, Ain

    2015-01-01

    Background: So far, the anticancer action of pine tree extracts has mainly been shown for the species distributed widely around the Asian countries. Objective: Therefore, this study was performed to examine the potential cytotoxicity of Scots pine (Pinus sylvestris L.) native also to the European region and growing widely in Estonia. Materials and Methods: The cytotoxic activity of methanol extract and essential oil of Scots pine needles was determined by sulforhodamine B assay in different human cancer cell lines. Results: This needle extract was found to suppress the viability of several human cancer cell lines showing some selectivity to estrogen receptor negative breast cancer cells, MDA-MB-231(half maximal inhibitory concentration [IC50] 35 μg/ml) in comparison with estrogen receptor-positive breast cancer cells, MCF-7 (IC50 86 μg/ml). It is the strongest cytotoxic effect at all measured, thus far for the needles and leaves extracts derived from various pine species, and is also the first study comparing the anticancer effects of pine tree extracts on molecularly different human breast cancer cells. The essential oil showed the stronger cytotoxic effect to both negative and positive breast cancer cell lines (both IC50 29 μg/ml) than pine extract (IC50 42 and 80 μg/ml, respectively). Conclusion: The data from this report indicate that Scots pine needles extract and essential oil exhibits some potential as chemopreventive or chemotherapeutic agent for mammary tumors unresponsive to endocrine treatment. PMID:26664017

  19. Genotoxicity of human milk extracts and detection of DNA damage in exfoliated cells recovered from breast milk.

    PubMed

    Martin, F L; Cole, K J; Weaver, G; Williams, J A; Millar, B C; Grover, P L; Phillips, D H

    1999-06-07

    Genotoxic agents of environmental or dietary origin may play a role in breast cancer initiation. The ability of extracts of human milk to cause mutations in S. typhimurium TA1538 and YG1019 and to induce micronuclei and DNA strand breaks in MCL-5 cells was investigated. Twenty samples from different donors were analysed and of these, 6 were adjudged to produce positive mutagenic response in one or both bacterial strains. The same samples also induced significant micronucleus formation in MCL-5 cells. In the comet assay, 13/20 samples caused DNA strand breaks in MCL-5 cells. Viable exfoliated breast cells were recovered from fresh milk samples and the ability of milk extracts to cause DNA damage in these cells was demonstrated. The results show that human milk can contain components capable of causing genotoxic damage in test systems and in human breast cells, events that may be significant in the initiation of breast cancer

  20. Genotoxicity of human milk extracts and detection of DNA damage in exfoliated cells recovered from breast milk.

    PubMed

    Martin, F L; Cole, K J; Weaver, G; Grover, P L; Phillips, D H

    1999-04-13

    Genotoxic agents of environmental or dietary origin may play a role in breast cancer initiation. The ability of extracts of human milk to cause mutations in S. typhimurium TA1538 and YG1019 and to induce micronuclei and DNA strand breaks in MCL-5 cells was investigated. Twenty samples from different donors were analysed and of these, 6 were adjudged to produce a positive mutagenic response in one or both bacterial strains. The same samples also induced significant micronucleus formation in MCL-5 cells. In the comet assay, 13/20 samples caused DNA strand breaks in MCL-5 cells. Viable exfoliated breast cells were recovered from fresh milk samples and the ability of milk extracts to cause DNA damage in these cells was demonstrated. The results show that human milk can contain components capable of causing genotoxic damage in test systems and in human breast cells, events that may be significant in the initiation of breast cancer.

  1. Filtering, Segmentation and Feature Extraction in Ultrasound Evaluation of Breast Lesions

    NASA Astrophysics Data System (ADS)

    Alemán-Flores, Miguel; Alemán-Flores, Patricia; Álvarez-León, Luisá; Fuentes-Pavón, Rafael; Santana-Montesdeoca, José M.

    The early diagnosis of breast cancer depends in many cases on the analysis of medical imaging, mainly mammography, ultrasonography and MRI. This work deals with ultrasound images in order to reduce speckle noise, identify the contour of the nodules and analyze a wide range of criteria which allow distinguishing between benign and malignant tumors. We try to automatize the different phases of the process and extract some objective parameters for a robust and reproducible diagnosis. We provide the physicians with both graphical as well as numerical results for the features which have been analyzed.

  2. Breast cancer 1 (BrCa1) may be behind decreased lipogenesis in adipose tissue from obese subjects.

    PubMed

    Ortega, Francisco J; Moreno-Navarrete, José M; Mayas, Dolores; García-Santos, Eva; Gómez-Serrano, María; Rodriguez-Hermosa, José I; Ruiz, Bartomeu; Ricart, Wifredo; Tinahones, Francisco J; Frühbeck, Gema; Peral, Belen; Fernández-Real, José M

    2012-01-01

    Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1) interacts with acetyl-CoA carboxylase (ACC) reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. BrCa1 gene expression, total and phosphorylated (P-) BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002) and subcutaneous (SC; 1.49-fold, p = 0.001) adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007) as well as in OM (p = 0.010) fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001) and protein (1.2-fold, p = 0.001) were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005) allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium), whereas lipogenic genes significantly decreased. The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects.

  3. Aqueous Extracts of Hibiscus sabdariffa Calyces Decrease Hepatitis A Virus and Human Norovirus Surrogate Titers.

    PubMed

    Joshi, Snehal S; Dice, Lezlee; D'Souza, Doris H

    2015-12-01

    Hibiscus sabdariffa extract is known to have antioxidant, anti-diabetic, and antimicrobial properties. However, their effects against foodborne viruses are currently unknown. The objective of this study was to determine the antiviral effects of aqueous extracts of H. sabdariffa against human norovirus surrogates (feline calicivirus (FCV-F9) and murine norovirus (MNV-1)) and hepatitis A virus (HAV) at 37 °C over 24 h. Individual viruses (~5 log PFU/ml) were incubated with 40 or 100 mg/ml of aqueous hibiscus extract (HE; pH 3.6), protocatechuic acid (PCA; 3 or 6 mg/ml, pH 3.6), ferulic acid (FA; 0.5 or 1 mg/ml; pH 4.0), malic acid (10 mM; pH 3.0), or phosphate buffered saline (pH 7.2 as control) at 37 °C over 24 h. Each treatment was replicated thrice and plaque assayed in duplicate. FCV-F9 titers were reduced to undetectable levels after 15 min with both 40 and 100 mg/ml HE. MNV-1 was reduced by 1.77 ± 0.10 and 1.88 ± 0.12 log PFU/ml after 6 h with 40 and 100 mg/ml HE, respectively, and to undetectable levels after 24 h by both concentrations. HAV was reduced to undetectable levels by both HE concentrations after 24 h. PCA at 3 mg/ml reduced FCV-F9 titers to undetectable levels after 6 h, MNV-1 by 0.53 ± 0.01 log PFU/ml after 6 h, and caused no significant change in HAV titers. FA reduced FCV-F9 to undetectable levels after 3 h and MNV-1 and HAV after 24 h. Transmission electron microscopy showed no conclusive results. The findings suggest that H. sabdariffa extracts have potential to prevent foodborne viral transmission.

  4. Vascular endothelial growth factor A (VEGF-A) mRNA expression levels decrease after menopause in normal breast tissue but not in breast cancer lesions

    PubMed Central

    Greb, R R; Maier, I; Wallwiener, D; Kiesel, L

    1999-01-01

    We hypothesized that the regulation of microvascular functions and angiogenesis in breast tissue, a well known target of ovarian steroid action, is dependent on the hormonal exposure of the breast. Relative expression levels of VEGF-A (vascular endothelial growth factor A), a putative key regulator of angiogenesis in breast cancer, were analysed in the tumour and the adjacent non-neoplastic breast tissue of 19 breast cancer patients by quantitative reverse transcriptase polymerase chain reaction. In non-neoplastic breast specimens the expression levels of all detected VEGF-A-isoforms (189, 165, 121) were significantly higher in premenopausal compared to post-menopausal women (P = 0.02) and were inversely correlated with the patient's age (P = 0.006). In contrast, in cancerous tissues menopausal status had no influence on VEGF-A-expression levels. Benign and malignant tissues exhibited a similar expression pattern of VEGF-A-isoforms relative to each other. Thus, the regulation of the vasculature in normal breast tissue, as opposed to breast cancer tissue, appears to be hormonally dependent. Endogenous and therapeutically used hormonal steroids might, therefore, cause clinically relevant changes of the angiogenic phenotype of the human breast. © 1999 Cancer Research Campaign PMID:10496346

  5. Extraction of medically interpretable features for classification of malignancy in breast thermography.

    PubMed

    Madhu, Himanshu; Kakileti, Siva Teja; Venkataramani, Krithika; Jabbireddy, Susmija

    2016-08-01

    Thermography, with high-resolution cameras, is being re-investigated as a possible breast cancer screening imaging modality, as it does not have the harmful radiation effects of mammography. This paper focuses on automatic extraction of medically interpretable non-vascular thermal features. We design these features to differentiate malignancy from different non-malignancy conditions, including hormone sensitive tissues and certain benign conditions, which have an increased thermal response. These features increase the specificity for breast cancer screening, which had been a long known problem in thermographic screening, while retaining high sensitivity. These features are also agnostic to different cameras and resolutions (up to an extent). On a dataset of around 78 subjects with cancer and 187 subjects without cancer, that have some benign diseases and conditions with thermal responses, we are able to get around 99% specificity while having 100% sensitivity. This indicates a potential break-through in thermographic screening for breast cancer. This shows promise for undertaking a comparison to mammography with larger numbers of subjects with more data variations.

  6. Inhibition of human breast and colorectal cancer cells by Viburnum foetens L. extracts in vitro

    PubMed Central

    Waheed, Abdul; Bibi, Yamin; Nisa, Sobia; Chaudhary, Fayyaz M; Sahreen, Sumaira; Zia, Muhammad

    2013-01-01

    Objective To investigate efficacy of Viburnum foetens (V. foetens) extracts against different cancer lines. Methods The crude extract and fractions of V. foetens are evaluated against MDA MB-468 and Caco-2 cancer cell lines by using MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl- 2H-tetrazolium bromide) assays. These extracts are also tested against breast carcinoma and human colon adenocarcinoma through NRU (neutral red uptake) assay. Results The crude extract inhibited the cancerous cell growth in a dose dependent manner. From the MTT assay it is obvious that the ethylacetate fraction significantly inhibited the growth of Caco-2 (93.44%) cell. Similarly, the methanol and ethylacetate fractions shows 99% and 96% inhibition of MCF-7 and Caco-2 cell lines by NRU assay. Furthermore, the ethylacetate fraction also exhibited momentous inhibition of MDA MB-468 cells in both assays. Other fractions i.e. chloroform, hexane also inhibited cancer cell proliferation at a significant level. Natural products exhibited significant activity against multiple cancerous cells. Conclusions In this framework, we can speculate that the present study will be helpful in the identification and isolation of novel anticancer drug compounds from the crude extract (i.e., methanol and ethyl acetate fractions) of V. foetens.

  7. Activity Markers of the Anti-Breast Carcinoma Cell Growth Fractions of Vernonia amygdalina Extracts

    PubMed Central

    Oyugi, Daniel A.; Luo, Xuan; Lee, Ken S.; Hill, Brandon; Izevbigie, Ernest B.

    2010-01-01

    Vernonia amygdalina (VA) is an edible plant of the Asteraceae family used in many herbal formulations prescribed by herbalists for many diseases. We have previously reported that aqueous VA extracts inhibit the growth of estrogen receptor-positive human breast cancerous cells in vitro. Activity markers of the VA extracts have not been previously identified or characterized. Hence, the objective of this study was to identify activity markers of the VA extracts associated with cell growth inhibition. Extraction of VA with multiple solvents of various polarity indexes yielded three fractions (A1-2, B-3) that significantly inhibited cell growth (p <0.05) at 0.1 mg/ml concentration. At a higher concentration of 1 mg/ml, six fractions of hexane, chloroform, butanol, and ethyl acetate (A1-3, B2-4) inhibited DNA synthesis by 76, 98, 94, 98, 98, and 96% respectively. These fractions were UV-detected from 250–730 nm; and all showed three distinct peaks around 410, 431, and 664 nm. Furthermore, HPLC analysis of the fractions revealed similar retention times of 2.213, 2.167, and 2.151 min respectively. Bioactivity assays showed that HPLC retention of approximately 2 min is required for cell growth-inhibitory activity of VA fractions. Interestingly, all active fractions exhibited HPLC peaks at approximately 2 min. Therefore, the UV and HPLC peaks may be used as predictive tools to determine VA extracts activities. PMID:19176872

  8. Acetonic and Methanolic Extracts of Heterotheca inuloides, and Quercetin, Decrease CCl4-Oxidative Stress in Several Rat Tissues

    PubMed Central

    Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Cárdenas-Rodríguez, Noemí; Huerta-Gertrudis, Bernardino; García-Cruz, Mercedes Edna; Montesinos-Correa, Hortencia; Sánchez-González, Dolores Javier; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

    2013-01-01

    The present study was designed to test the hypothesis that the acetonic and methanolic extracts of H. inuloides prevent carbon tetrachloride-(CCl4) induced oxidative stress in vital tissues. Pretreatment with both H. inuloides extracts or quercetin attenuated the increase in serum activity of alkaline phosphatase (ALP), total bilirubin (BB), creatinine (CRE), and creatine kinase (CK), and impeded the decrease of γ-globulin (γ-GLOB) and albumin (ALB) observed in CCl4-induced tissue injury. The protective effect was confirmed by histological analysis with hematoxylin-eosin and periodic acid/Schiff's reagent. Level of lipid peroxidation was higher in the organs of rats exposed to CCl4 than in those of the animals treated with Heterohteca extracts or quercetin, and these showed levels similar to the untreated group. Pretreatment of animals with either of the extracts or quercetin also prevented the increase of 4-hydroxynonenal and 3-nitrotyrosine. Pretreatment with the plant extracts or quercetin attenuated CCl4 toxic effects on the activity of several antioxidant enzymes. The present results strongly suggest that the chemopreventive effect of the extracts used and quercetin, against CCl4 toxicity, is associated with their antioxidant properties and corroborated previous results obtained in liver tissue. PMID:23365610

  9. Tucumã fruit extracts (Astrocaryum aculeatum Meyer) decrease cytotoxic effects of hydrogen peroxide on human lymphocytes.

    PubMed

    Sagrillo, Michele Rorato; Garcia, Luiz Filipe Machado; de Souza Filho, Olmiro Cezimbra; Duarte, Marta Maria Medeiros Frescura; Ribeiro, Euler Esteves; Cadoná, Francine Carla; da Cruz, Ivana Beatrice Mânica

    2015-04-15

    This study quantifies the bioactive molecules in and determines the in vitro protective effect of ethanolic extracts isolated from the peel and pulp of tucumã (Astrocaryum aculeatum, Mart.), an Amazonian fruit rich in carotenoids. The cytoprotective effect of tucumã was evaluated in lymphocyte cultures exposed to H2O2 using spectrophotometric, fluorimetric, and immunoassay assays. The results confirmed that tucumã pulp extract is rich in β-carotene and quercetin, as previously described in the literature. However, high levels of these compounds were also found in tucumã peel extract. The extracts also contained significant amounts rutin, gallic acid, caffeic acid, and chlorogenic acid. Despite quantitative differences in the concentration of these bioactive molecules, both extracts increased the viability of cells exposed to H2O2 in concentrations ranging from 300 to 900 μg/mL. Caspases 1, 3, and 8 decreased significantly in cells concomitantly exposed to H2O2 and these extracts, indicating that tucumã cryoprotection involves apoptosis modulation.

  10. Wheat germ extract decreases glucose uptake and RNA ribose formation but increases fatty acid synthesis in MIA pancreatic adenocarcinoma cells.

    PubMed

    Boros, L G; Lapis, K; Szende, B; Tömösközi-Farkas, R; Balogh, A; Boren, J; Marin, S; Cascante, M; Hidvégi, M

    2001-08-01

    The fermented wheat germ extract with standardized benzoquinone composition has potent tumor propagation inhibitory properties. The authors show that this extract induces profound metabolic changes in cultured MIA pancreatic adenocarcinoma cells when the [1,2-13C2]glucose isotope is used as the single tracer with biologic gas chromatography-mass spectrometry. MIA cells treated with 0.1, 1, and 10 mg/mL wheat germ extract showed a dose-dependent decrease in cell glucose consumption. uptake of isotope into ribosomal RNA (2.4%, 9.4%, and 28.0%), and release of 13CO2. Conversely, direct glucose oxidation and ribose recycling in the pentose cycle showed a dose-dependent increase of 1.2%, 20.7%, and 93.4%. The newly synthesized fraction of cell palmitate and the 13C enrichment of acetyl units were also significantly increased with all doses of wheat germ extract. The fermented wheat germ extract controls tumor propagation primarily by regulating glucose carbon redistribution between cell proliferation-related and cell differentiation-related macromolecules. Wheat germ extract treatment is likely associated with the phosphorylation and transcriptional regulation of metabolic enzymes that are involved in glucose carbon redistribution between cell proliferation-related structural and functional macromolecules (RNA, DNA) and the direct oxidative degradation of glucose, which have devastating consequences for the proliferation and survival of pancreatic adenocarcinoma cells in culture.

  11. Acetonic and Methanolic Extracts of Heterotheca inuloides, and Quercetin, Decrease CCl(4)-Oxidative Stress in Several Rat Tissues.

    PubMed

    Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Cárdenas-Rodríguez, Noemí; Huerta-Gertrudis, Bernardino; García-Cruz, Mercedes Edna; Montesinos-Correa, Hortencia; Sánchez-González, Dolores Javier; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

    2013-01-01

    The present study was designed to test the hypothesis that the acetonic and methanolic extracts of H. inuloides prevent carbon tetrachloride-(CCl(4)) induced oxidative stress in vital tissues. Pretreatment with both H. inuloides extracts or quercetin attenuated the increase in serum activity of alkaline phosphatase (ALP), total bilirubin (BB), creatinine (CRE), and creatine kinase (CK), and impeded the decrease of γ-globulin (γ-GLOB) and albumin (ALB) observed in CCl(4)-induced tissue injury. The protective effect was confirmed by histological analysis with hematoxylin-eosin and periodic acid/Schiff's reagent. Level of lipid peroxidation was higher in the organs of rats exposed to CCl(4) than in those of the animals treated with Heterohteca extracts or quercetin, and these showed levels similar to the untreated group. Pretreatment of animals with either of the extracts or quercetin also prevented the increase of 4-hydroxynonenal and 3-nitrotyrosine. Pretreatment with the plant extracts or quercetin attenuated CCl(4) toxic effects on the activity of several antioxidant enzymes. The present results strongly suggest that the chemopreventive effect of the extracts used and quercetin, against CCl(4) toxicity, is associated with their antioxidant properties and corroborated previous results obtained in liver tissue.

  12. Growth inhibitory activity of extracts and compounds from Cimicifuga species on human breast cancer cells.

    PubMed

    Einbond, Linda Saxe; Wen-Cai, Ye; He, Kan; Wu, Hsan-au; Cruz, Erica; Roller, Marc; Kronenberg, Fredi

    2008-06-01

    The purpose of this report is to explore the growth inhibitory effect of extracts and compounds from black cohosh and related Cimicifuga species on human breast cancer cells and to determine the nature of the active components. Black cohosh fractions enriched for triterpene glycosides and purified components from black cohosh and related Asian species were tested for growth inhibition of the ER(-) Her2 overexpressing human breast cancer cell line MDA-MB-453. Growth inhibitory activity was assayed using the Coulter Counter, MTT and colony formation assays. Results suggested that the growth inhibitory activity of black cohosh extracts appears to be related to their triterpene glycoside composition. The most potent Cimicifuga component tested was 25-acetyl-7,8-didehydrocimigenol 3-O-beta-d-xylopyranoside, which has an acetyl group at position C-25. It had an IC(50) of 3.2microg/ml (5microM) compared to 7.2microg/ml (12.1microM) for the parent compound 7,8-didehydrocimigenol 3-O-beta-d-xylopyranoside. Thus, the acetyl group at position C-25 enhances growth inhibitory activity. The purified triterpene glycoside actein (beta-d-xylopyranoside), with an IC(50) equal to 5.7microg/ml (8.4microM), exhibited activity comparable to cimigenol 3-O-beta-d-xyloside. MCF7 (ER(+)Her2 low) cells transfected for Her2 are more sensitive than the parental MCF7 cells to the growth inhibitory effects of actein from black cohosh, indicating that Her2 plays a role in the action of actein. The effect of actein on Her2 overexpressing MDA-MB-453 and MCF7 (ER(+)Her2 low) human breast cancer cells was examined by fluorescent microscopy. Treatment with actein altered the distribution of actin filaments and induced apoptosis in these cells. These findings, coupled with our previous evidence that treatment with the triterpene glycoside actein induced a stress response and apoptosis in human breast cancer cells, suggest that compounds from Cimicifuga species may be useful in the prevention and

  13. Can wood-inhabiting fungi remove extractives and decrease pitch problems?

    SciTech Connect

    Breuil, C.

    1996-10-01

    Biological treatments with lipases or esterases, and with microorganism such as Cartapip, have been tested with some success in laboratory and mill trials as new methods for reducing pitch problems in pulp and paper production. Usually pitch problems originate with the wood species pulped and depend on the pulping process. Although most wood species contain similar lipid classes (triglycerides, fatty acids, steryl esters, sterols and other non-saponifiables), the proportion of the different classes varies between sapwood and heartwood and between species. Consequently, the behavior of extractives from different wood supplies is difficult to predict. Similarly, the efficiency of a biological treatment can be significantly affected by physical and chemical conditions in the wood being treated. The beneficial effect of such a treatment can be significantly reduced by high extractive concentrations, low levels or unavailability of nutrients required to support microbial growth (especially nitrogen). The effects of some of these factors on biotreatments can be reduced by modifying wood, or the overall treatment. Handling other factors may require finding or perhaps improving new types of microorganisms.

  14. Isoflavones extracted from chickpea Cicer arietinum L. sprouts induce mitochondria-dependent apoptosis in human breast cancer cells.

    PubMed

    Chen, Hua; Ma, Hai-Rong; Gao, Yan-Hua; Zhang, Xue; Habasi, Madina; Hu, Rui; Aisa, Haji Akber

    2015-02-01

    Isoflavones are important chemical components of the seeds and sprouts of chickpeas. We systematically investigated the effects of isoflavones extracted from chickpea sprouts (ICS) on the human breast cancer cell lines SKBr3 and Michigan Cancer Foundation-7 (MCF-7). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed that ICS (10-60 µg/mL) significantly inhibited the proliferation of both cell lines in a time-dependent and dose-dependent fashion. Wright-Giemsa staining as well as annexin V-fluorescein isothiocyanate and propidium iodide (Annexin V/PI) staining showed that ICS significantly increased cytoclasis and apoptotic body formation. Quantitative Annexin V/PI assays further showed that the number of apoptotic cells increased in a dose-dependent manner following ICS treatment. Semiquantitative reverse transcription PCR showed that ICS increased the expression of the apoptosis-promoting gene Bcl-2-associated X protein and decreased the expression of the antiapoptotic gene Bcl-2. Western blot analysis showed that treatment of SKBr3 and MCF-7 cells with ICS increased the expression of caspase 7, caspase 9, P53, and P21 in a dose-dependent manner. Flow cytometry assays using the fluorescent probe 3,3'-dihexyloxacarbocyanine iodide showed a dose-dependent decrease in mitochondrial membrane potential following ICS treatment. Treatment using ICS also induced a dose-dependent increase in reactive oxygen species production. This is the first study to demonstrate that ICS may be a chemopreventive or therapeutic agent against breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Bovine dialyzable leukocyte extract modulates AP-1 DNA-binding activity and nuclear transcription factor expression in MCF-7 breast cancer cells.

    PubMed

    Mendoza-Gamboa, E; Franco-Molina, M A; Zapata-Benavides, P; Castillo-Tello, P; Vera-García, M E; Tamez-Guerra, R S; Rodríguez-Padilla, C

    2008-01-01

    We have previously demonstrated that bovine dialyzable leukocyte extract (bDLE) induces death through an apoptosis mechanism in MCF-7 breast cancer cells. Depending on the cell type and stimulus, activating protein-1 (AP-1) has been shown to regulate cell proliferation and differentiation, the stress response, apoptosis and survival. It remains unknown whether AP-1 and other transcription factors are mechanisms by which bDLE induces cell death. To determine whether bDLE modulates the AP-1 DNA binding and gene expression, MCF-7 breast cancer cells were treated with bDLE (0, 1, 5, 10 U) for 72 h and evaluated by electrophoretic mobility shift assay, reverse transcriptase-polymerase chain reaction and Western blot assays. bDLE induced inhibition of cell growth, suppressed the AP-1 DNA-binding activity, decreased c-Jun protein expression and modulated NFATx, NFATc, NFkappaB, c-Jun and c-Fos transcription factor gene expression in MCF-7 breast cancer cells. The present data indicate that bDLE can block the AP-1 DNA-binding activity and expression of several transcriptions factors in breast cancer cells, which will have great potential in improving cancer therapy.

  16. Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome

    PubMed Central

    2014-01-01

    Background The insufficient metabolic adaptation to exercise in Chronic Fatigue Syndrome (CFS) is still being debated and poorly understood. Methods We analysed the cardiopulmonary exercise tests of CFS patients, idiopathic chronic fatigue (CFI) patients and healthy visitors. Continuous non-invasive measurement of the cardiac output by Nexfin® (BMEYE B.V. Amsterdam, the Netherlands) was added to the cardiopulmonary exercise tests. The peak oxygen extraction by muscle cells and the increase of cardiac output relative to the increase of oxygen uptake (ΔQ’/ΔV’O2) were measured, calculated from the cardiac output and the oxygen uptake during incremental exercise. Results The peak oxygen extraction by muscle cells was 10.83 ± 2.80 ml/100ml in 178 CFS women, 11.62 ± 2.90 ml/100 ml in 172 CFI, and 13.45 ± 2.72 ml/100 ml in 11 healthy women (ANOVA: P=0.001), 13.66 ± 3.31 ml/100 ml in 25 CFS men, 14.63 ± 4.38 ml/100 ml in 51 CFI, and 19.52 ± 6.53 ml/100 ml in 7 healthy men (ANOVA: P=0.008). The ΔQ’/ΔV’O2 was > 6 L/L (normal ΔQ’/ΔV’O2 ≈ 5 L/L) in 70% of the patients and in 22% of the healthy group. Conclusion Low oxygen uptake by muscle cells causes exercise intolerance in a majority of CFS patients, indicating insufficient metabolic adaptation to incremental exercise. The high increase of the cardiac output relative to the increase of oxygen uptake argues against deconditioning as a cause for physical impairment in these patients. PMID:24456560

  17. Jodina rhombifolia leaves lyophilized aqueous extract decreases ethanol intake and preference in adolescent male Wistar rats.

    PubMed

    Roberto Teves, Mauricio; Wendel, Graciela Haydée; Pelzer, Lilian Eugenia

    2015-11-04

    The leaves of Jodina rhombifolia (Hook. & Arn.) Reissek (Santalaceae) are utilized as anti-alcoholic in Argentine folk medicine. This study was designed to investigate the anti-alcohol properties in adolescent male Wistar rats (postnatal day 29; 83-105 g of weight). We utilized the "self-administration model", which ethanol was offered in the standard home-cage through two-bottle free-choice regimen between an ethanolic solution (20% in tap water, v/v) and tap water with unlimited access for 24h per day for 10 consecutive days. The results obtained show that repeated administration of J. rhombifolia lyophilized extract, markedly reduced ethanol voluntary intake on dose dependent bases. The magnitude in reduction of daily ethanol intake was approximately 29%, 44% and 68%, for the rat groups treated with 62.5, 125 and 250 mg/kg of extract, respectively. Ethanol preference (proportion of ethanol intake versus total fluid intake) was significantly reduced: 21.37% ± 0.79 (0 mg/kg); 15.83% ± 0.93 (62.5 mg/kg); 15.22% ± 1.30 (125 mg/kg) and 9.38% ± 0.57 (250 mg/kg). Daily food intake was significantly higher (p<0.05) in the group treated with 250 mg/kg of JRLE in comparison with vehicle-dose group; the reduction in ethanol intake was associated with a compensatory increase in food intake, probably because in the control group animals a part of the total caloric intake was supplied by ethanol. Treatment was very well tolerated by all animals and without apparent side-effects. These results contribute to the scientific validation of the antialcoholic indication of this botanic species in Argentine folk medicine.

  18. Circular RNA hsa_circ_0001982 Promotes Breast Cancer Cell Carcinogenesis Through Decreasing miR-143.

    PubMed

    Tang, Yi-Yin; Zhao, Ping; Zou, Tian-Ning; Duan, Jia-Jun; Zhi, Rong; Yang, Si-Yuan; Yang, De-Chun; Wang, Xiao-Li

    2017-09-21

    Circular RNAs (circRNAs) are a type of noncoding RNAs generated from back-splicing, which have been verified to mediate multiple tumorigenesis. With the development of high-throughput sequencing, massive circRNAs are discovered in tumorous tissue. However, the potential physiological effect of circRNAs in breast cancer is still unknown. The purpose of this study is to investigate the expression profile of circRNA in breast cancer tissue and explore the in-depth regulatory mechanism in breast cancer tumorigenesis. In the present study, we screened the circRNA expression profiles in breast cancer tissue using circRNA microarray analysis. Totally 1705 circRNAs were identified to be significantly aberrant. Among these dysregulated circRNAs, hsa_circ_0001982 was markedly overexpressed in breast cancer tissue and cell lines. Bioinformatics analysis predicted that miR-143 acted as target of hsa_circ_0001982, which was confirmed by Dual-luciferase reporter assay. Loss-of-function and rescue experiments revealed that hsa_circ_0001982 knockdown suppressed breast cancer cell proliferation and invasion and induced apoptosis by targeting miR-143. In summary, our study preliminarily investigates the circRNA expression in breast cancer tissue and explores the role of competing endogenous RNA (ceRNA) mechanism in the progression, providing a novel insight for breast cancer tumorigenesis.

  19. Cytotoxic Activity of the Methanolic Extract of Turnera diffusa Willd on Breast Cancer Cells

    PubMed Central

    Avelino-Flores, María del Carmen; Cruz-López, María del Carmen; Jiménez-Montejo, Fabiola E.; Reyes-Leyva, Julio

    2015-01-01

    Abstract Turnera diffusa Willd, commonly known as Damiana, is employed in traditional medicine as a stimulant, aphrodisiac, and diuretic. Its leaves and stems are used for flavoring and infusion. Damiana is considered to be safe for medicinal use by the FDA. Pharmacological studies have established the hypoglycemic, antiaromatase, prosexual, estrogenic, antibacterial, and antioxidant activity of T. diffusa. The aim of the present study was to evaluate the possible cytotoxic effect of extracts and organic fractions of this plant on five tumor cell lines (SiHa, C-33, Hep G2, MDA-MB-231, and T-47D) and normal human fibroblasts. The results show that the methanolic extract (TdM) displayed greater activity on MDA-MB-231 breast cancer cells (with an IC50 of 30.67 μg/mL) than on the other cancer cell lines. Four organic fractions of this extract exhibited activity on this cancer cell line. In the most active fraction (F4), two active compounds were isolated, arbutin (1) and apigenin (2). This is the first report of a cytotoxic effect by T. diffusa on cancer cells. The IC50 values suggest that the methanolic extract of T. diffusa has potential as an anticancer therapy. PMID:25299247

  20. The Inhibitory Effect of Bamboo Extract on the Development of 7,12-Dimethylbenz[a]anthracene (DMBA)-induced Breast Cancer

    PubMed Central

    Lin, Yanling; Collier, Abby C.; Liu, Wanyu; Berry, Marla J.; Panee, Jun

    2015-01-01

    The incidence of breast cancer among women is high and increasing. This study investigated the inhibitory effect of an extract from bamboo Phyllostachys edulis on the development of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer in female Sprague-Dawley rats. The rats were fed with bamboo extract (BEX) supplemented diet or control diet, and treated with DMBA after 3 weeks of the dietary regime. The incidence of mammary tumors was monitored by palpation for the next 11 weeks. At the end of the experiment, blood samples were collected for total antioxidant capacities (TAC) assay and liver samples for phase II enzyme activity assays. The TAC values, total contents of phenolics and flavonoids of BEX were also measured. The results showed that BEX delayed the onset of mammary tumor by 1 week, decreased the tumor incidence by 44% and tumor multiplicity by 67%, and increased the total sulfotransferases (SULT) activity by 63%. BEX showed high levels of TAC, total phenolic and total flavonoids. However, the serum TAC values were not affected by BEX supplementation. In summary, the results indicate that BEX possesses a potent anti-breast cancer effect, and the upregulation of SULT activity, therefore estrogen metabolism may be the underlying mechanism. PMID:18972584

  1. Radiation dose reduction to the breast in thoracic CT: Comparison of bismuth shielding, organ-based tube current modulation, and use of a globally decreased tube current

    SciTech Connect

    Wang Jia; Duan Xinhui; Christner, Jodie A.; Leng Shuai; Yu Lifeng; McCollough, Cynthia H.

    2011-11-15

    Purpose: The purpose of this work was to evaluate dose performance and image quality in thoracic CT using three techniques to reduce dose to the breast: bismuth shielding, organ-based tube current modulation (TCM) and global tube current reduction. Methods: Semi-anthropomorphic thorax phantoms of four different sizes (15, 30, 35, and 40 cm lateral width) were used for dose measurement and image quality assessment. Four scans were performed on each phantom using 100 or 120 kV with a clinical CT scanner: (1) reference scan; (2) scan with bismuth breast shield of an appropriate thickness; (3) scan with organ-based TCM; and (4) scan with a global reduction in tube current chosen to match the dose reduction from bismuth shielding. Dose to the breast was measured with an ion chamber on the surface of the phantom. Image quality was evaluated by measuring the mean and standard deviation of CT numbers within the lung and heart regions. Results: Compared to the reference scan, dose to the breast region was decreased by about 21% for the 15-cm phantom with a pediatric (2-ply) shield and by about 37% for the 30, 35, and 40-cm phantoms with adult (4-ply) shields. Organ-based TCM decreased the dose by 12% for the 15-cm phantom, and 34-39% for the 30, 35, and 40-cm phantoms. Global lowering of the tube current reduced breast dose by 23% for the 15-cm phantom and 39% for the 30, 35, and 40-cm phantoms. In phantoms of all four sizes, image noise was increased in both the lung and heart regions with bismuth shielding. No significant increase in noise was observed with organ-based TCM. Decreasing tube current globally led to similar noise increases as bismuth shielding. Streak and beam hardening artifacts, and a resulting artifactual increase in CT numbers, were observed for scans with bismuth shields, but not for organ-based TCM or global tube current reduction. Conclusions: Organ-based TCM produces dose reduction to the breast similar to that achieved with bismuth shielding for

  2. Breast cancer in South-Eastern European countries since 2000: Rising incidence and decreasing mortality at young and middle ages.

    PubMed

    Dimitrova, Nadya; Znaor, Ariana; Agius, Dominic; Eser, Sultan; Sekerija, Mario; Ryzhov, Anton; Primic-Žakelj, Maja; Coebergh, Jan Willem

    2017-09-01

    Marked variations exist in the incidence and mortality trends of major cancers in South-Eastern European (SEE) countries which have now been detailed by age for breast cancer (BC) to seek clues for improvement. We brought together and analysed data from 14 cancer registries (CRs), situated in SEE countries or directly adjacent. Age-standardised rate at world standard (ASRw) and truncated incidence and mortality rates during 2000-2010 by year, and for four age groups, were calculated. Average annual percentage change of rates was estimated using Joinpoint regression. Annual incidence rates increased significantly in countries and age groups, by 2-4% (15-39 years), 2-5% (40-49), 1-4% (50-69) and 1-6% (at 70+). Mortality rates decreased significantly in all age-groups in most countries, but increased up to 5% annually above age 55 in Ukraine, Serbia, Moldova and Cyprus. The BC data quality was evaluated by internationally agreed indicators which appeared suboptimal for Moldova, Bosnia and Herzegovina and Romania. The observed variations of incidence trends reflect the influence of risk factors, as well as levels of early detection activities (screening). While mortality rates were mostly decreasing, probably due to improved cancer care and introduction of more effective systemic treatment regimens, the worrying increasing mortality trends in the 55-plus age groups in some countries have to be addressed by health professionals and policymakers. In order to assess and monitor the effects of cancer control activities in the region, the CRs need substantial investments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Does Breast Magnetic Resonance Imaging Combined With Conventional Imaging Modalities Decrease the Rates of Surgical Margin Involvement and Reoperation?: A Case-Control Comparative Analysis.

    PubMed

    Lai, Hung-Wen; Chen, Chih-Jung; Lin, Ying-Jen; Chen, Shu-Ling; Wu, Hwa-Koon; Wu, Yu-Ting; Kuo, Shou-Jen; Chen, Shou-Tung; Chen, Dar-Ren

    2016-05-01

    The objective of this study was to assess whether preoperative breast magnetic resonance imaging (MRI) combined with conventional breast imaging techniques decreases the rates of margin involvement and reexcision.Data on patients who underwent surgery for primary operable breast cancer were obtained from the Changhua Christian Hospital (CCH) breast cancer database. The rate of surgical margin involvement and the rate of reoperation were compared between patients who underwent conventional breast imaging modalities (Group A: mammography and sonography) and those who received breast MRI in addition to conventional imaging (Group B: mammography, sonography, and MRI).A total of 1468 patients were enrolled in this study. Among the 733 patients in Group A, 377 (51.4%) received breast-conserving surgery (BCS) and 356 (48.6%) received mastectomy. Among the 735 patients in Group B, 348 (47.3%) received BCS and 387 (52.7%) received mastectomy. There were no significant differences in operative method between patients who received conventional imaging alone and those that received MRI and conventional imaging (P = 0.13). The rate of detection of pathological multifocal/multicentric breast cancer was markedly higher in patients who received preoperative MRI than in those who underwent conventional imaging alone (14.3% vs 8.6%, P < 0.01). The overall rate of surgical margin involvement was significantly lower in patients who received MRI (5.0%) than in those who received conventional imaging alone (9.0%) (P < 0.01). However, a significant reduction in rate of surgical margin positivity was only observed in patients who received BCS (Group A, 14.6%; Group B, 6.6%, P < 0.01). The overall BCS reoperation rates were 11.7% in the conventional imaging group and 3.2% in the combined MRI group (P < 0.01). There were no significant differences in rate of residual cancer in specimens obtained during reoperation between the 2 preoperative imaging groups (Group A, 50

  4. Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells.

    PubMed

    Plastina, Pierluigi; Bonofiglio, Daniela; Vizza, Donatella; Fazio, Alessia; Rovito, Daniela; Giordano, Cinzia; Barone, Ines; Catalano, Stefania; Gabriele, Bartolo

    2012-03-27

    Ziziphus extracts have been used in Traditional Chinese Medicine for the treatment of cancer. In the present study we have investigated the effects of Ziziphus jujube extracts (ZEs) on breast cancer. We evaluated the effects of increasing concentrations of ZEs on ERα positive MCF-7 and ERα negative SKBR3 breast cancer cell proliferation using MTT assays. Apoptosis was analyzed by evaluating the involvement of some pro-apoptotic proteins, including Bax, Bad, Bid and PARP cleavage by immunoblotting analysis. Moreover, the effects of ZEs treatment on apoptosis were tested by both DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining. By using chromatographic techniques, we identified the constituents of the effective extracts. ZE1, ZE2, and ZE4 exerted significant antiproliferative effects on estrogen receptor alpha (ERα) positive MCF-7 (IC(50) values of 14.42, 7.64, 1.69μg/mL) and ERα negative SKBR3 (IC(50) values of 14.06, 6.21, 3.70μg/mL) human breast cancer cells. Remarkably, ZEs did not affect cell viability of both normal human fibroblasts BJ1-hTERT and nonmalignant breast epithelial MCF-10A cells. Treatment with ZEs induced cell death by apoptosis in both malignant breast cells. We found that the most effective extracts ZE2 and ZE4 shared a number of triterpenic acids, already known for their anticancer activities. Our data provide a rational base for the use of Ziziphus extracts in the treatment of breast cancer in Traditional Chinese Medicine. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  5. Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line.

    PubMed

    Tan, M L; Sulaiman, S F; Najimuddin, N; Samian, M R; Muhammad, T S Tengku

    2005-01-04

    Currently, breast cancer is the leading cause of cancer-related death in women. Therefore, there is an urgent need to develop alternative therapeutic measures against this deadly disease. Here, we report the cytotoxicity activity and the mechanism of cell death exhibited by the methanol extract prepared from Pereskia bleo (Kunth) DC. (Cactaceae) plant against human breast carcinoma cell line, T-47D. In vitro cytotoxicity screening of methanol extract of Pereskia bleo plant indicated the presence of cytotoxicity activity of the extract against T-47D cells with EC50 of 2.0 microg/ml. T-47D cell death elicited by the extract was found to be apoptotic in nature based a clear indication of DNA fragmentation which is a hallmark of apoptosis. In addition, ultrastructural analysis also revealed apoptotic characteristics (the presence of chromatin margination and apoptotic bodies) in the extract-treated cells. RT-PCR analysis showed the mRNA expression levels of c-myc, and caspase 3 were markedly increased in the cells treated with the plant extract. However, p53 expression was only slightly increased as compared to caspase 3 and c-myc. Thus, the results from this study strongly suggest that the methanol extract of Pereskia bleo may contain bioactive compound(s) that caused breast carcinoma, T-47D cell death by apoptosis mechanism via the activation of caspase-3 and c-myc pathways.

  6. Breast Cancer 1 (BrCa1) May Be behind Decreased Lipogenesis in Adipose Tissue from Obese Subjects

    PubMed Central

    Ortega, Francisco J.; Moreno-Navarrete, José M.; Mayas, Dolores; García-Santos, Eva; Gómez-Serrano, María; Rodriguez-Hermosa, José I.; Ruiz, Bartomeu; Ricart, Wifredo; Tinahones, Francisco J.; Frühbeck, Gema; Peral, Belen; Fernández-Real, José M.

    2012-01-01

    Context Expression and activity of the main lipogenic enzymes is paradoxically decreased in obesity, but the mechanisms behind these findings are poorly known. Breast Cancer 1 (BrCa1) interacts with acetyl-CoA carboxylase (ACC) reducing the rate of fatty acid biosynthesis. In this study, we aimed to evaluate BrCa1 in human adipose tissue according to obesity and insulin resistance, and in vitro cultured adipocytes. Research Design and Methods BrCa1 gene expression, total and phosphorylated (P-) BrCa1, and ACC were analyzed in adipose tissue samples obtained from a total sample of 133 subjects. BrCa1 expression was also evaluated during in vitro differentiation of human adipocytes and 3T3-L1 cells. Results BrCa1 gene expression was significantly up-regulated in both omental (OM; 1.36-fold, p = 0.002) and subcutaneous (SC; 1.49-fold, p = 0.001) adipose tissue from obese subjects. In parallel with increased BrCa1 mRNA, P-ACC was also up-regulated in SC (p = 0.007) as well as in OM (p = 0.010) fat from obese subjects. Consistent with its role limiting fatty acid biosynthesis, both BrCa1 mRNA (3.5-fold, p<0.0001) and protein (1.2-fold, p = 0.001) were increased in pre-adipocytes, and decreased during in vitro adipogenesis, while P-ACC decreased during differentiation of human adipocytes (p = 0.005) allowing lipid biosynthesis. Interestingly, BrCa1 gene expression in mature adipocytes was restored by inflammatory stimuli (macrophage conditioned medium), whereas lipogenic genes significantly decreased. Conclusions The specular findings of BrCa1 and lipogenic enzymes in adipose tissue and adipocytes reported here suggest that BrCa1 might help to control fatty acid biosynthesis in adipocytes and adipose tissue from obese subjects. PMID:22666314

  7. Pomegranate peel extract decreases small intestine lipid peroxidation by enhancing activities of major antioxidant enzymes.

    PubMed

    Al-Gubory, Kaïs H; Blachier, François; Faure, Patrice; Garrel, Catherine

    2016-08-01

    Pomegranate peel extract (PPE) contains several compounds with antioxidative properties. PPE added to foods may interact with endogenous antioxidants and promote health. However, little is known about the biochemical mechanisms by which PPE exerts their actions on tissues of biological systems in vivo. The purpose of this study was to determine the effects of PPE on activities of antioxidant enzymes. Mice were used to investigate the effects of PPE on plasma levels of malondialdehyde (MDA), tissue MDA content and activities of superoxide dismutase 1 (SOD1), SOD2 and glutathione peroxidase (GPX) in the small intestine, liver and skeletal muscle - different tissues involved in the digestion, absorption and metabolism of dietary nutrients. Control mice were fed a standard diet, whereas treated mice were fed for 40 days with the standard diet containing 5% or 10% PPE. Mice fed the 10% PPE diet exhibited lower plasma MDA concentrations, reduced content of MDA in the small intestine and liver and higher levels of SOD1 and GPX activities in the small intestine compared to mice fed the control diet. These findings demonstrate that intake of PPE in diet attenuates small intestine lipid peroxidation and strengthens the first line of small intestine antioxidant defense by enhancing enzymatic antioxidative pathways. PPE is worthy of further study as a therapeutic approach to prevent peroxidative stress-induced gut pathogenesis. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  8. Decreasing cariogenic bacteria with a natural, alternative prevention therapy utilizing phytochemistry (plant extracts).

    PubMed

    Ramakrishna, Y; Goda, H; Baliga, M S; Munshi, A K

    2011-01-01

    The association between the oral microbiota and oral diseases is well established. Various antimicrobial agents including antibiotics are commercially available against oral pathogenic bacteria. For the reasons of antibiotic resistance, their adverse effects and financial considerations in the developing countries, there is a need for alternate preventive and curative treatment options that are also safe, effective and economical. Traditional medicines have been used since ancient times for the treatment of oral diseases including dental caries, periodontal diseases that affect the majority of the population and can affect a person's overall health. Natural phytochemicals are certain organic components isolated from plants and some of these extracts are considered to be beneficial to health. They serve as antioxidants, enhance immune response, provide protection against oral cancer and other diseases and also repair DNA damage caused by smoking and other toxic exposure, and detoxify carcinogens. The natural products derived from medicinal plants have proven to be an abundant source of biologically active compounds, many of which have been the basis for the development of new lead chemicals for pharmaceuticals. They are considered to be good alternatives to synthetic chemicals. This article presents a review of natural alternatives derived from plants and plant products that can serve as a prevention and treatment option against cariogenic bacteria.

  9. [Decreased insulin resistance with amino acids, extracts and antioxidants in patients with polycystic ovary syndrome].

    PubMed

    Hernández-Valencia, Marcelino; Hernández-Quijano, Tomás; Vargas-Girón, Antonio; Vargas-López, Carlos; Arturo-Zárate

    2013-10-01

    The polycystic ovary syndrome (PCOS) it is a metabolic disorder with insulin resistance associated. Have been recently described contributor factors in the presence of insulin resistance that need to be studied. These factors can be the nutrients in the daily diet, final products of the advanced glycated end-products (AGEs), reactive derivatives of non enzymatic glucose-protein reactions either produced endogenously or ingested from dietary sources. The aim was to modifies the food intake to know the contribution on improve insulin resistance. Compare different diets and changes in insulin resistance in patients with polycystic ovary syndrome. As longitudinal, prospective and descriptive study, were included women with age among 18 to 40 years who received a compound with amino acids, extracts and anti-oxidants to dose of 660mg every 8 hours for 6 months. The inclusion approaches included the insulin resistance presence HOMA-IR > 2.6, elevated LH, and presence of ovaries with cysts by ultrasound. Statistical analysis with ANOVA one way to p <0.05. Were included a total of 30 patients, of which 28 patients had improvement in the insulin resistance from the 3 months, but until the 6 months they had significant difference (p<0.05), compared with 24 women from control group. With this result is demonstrated that it is necessary to modify the diet and to offer alimentary support to avoid the oxidative stress that takes impairment the insulin signaling with the subsequent insulin resistance.

  10. Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice

    PubMed Central

    Zhang, Lei; Shamaladevi, Nagarajarao; Jayaprakasha, Guddadarangavvanahally K.; Patil, Bhimu S.; Lokeshwar, Bal L.

    2015-01-01

    Bioactive compounds from edible plants have limited efficacy in treating advanced cancers, but they have potential to increase the efficacy of chemotherapy drugs in a combined treatment. An aqueous extract of berries of Pimenta dioica (Allspice) shows promise as one such candidate for combination therapy or chemoprevention. An aqueous extract of Allspice (AAE) was tested against human breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and clonogenic growth of several types of BrCa cells (IC50 ≤ 100 μg/ml) with limited toxicity in non-tumorigenic, quiescent cells (IC50 >200 μg/ml). AAE induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated with increased levels of autophagy markers LC3B and LC3B-positive puncta. Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not significantly (mean decrease ~ 14%, p ≥ 0.20) if mice were gavaged post-tumor implant. Tumor growth showed a significant delay (38%) in tumor palpability and growth rate (time to reach tumor volume ≥ 1,000 mm3) when mice were pre-dosed with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in treated mice. These results demonstrate antitumor and chemo-preventive activity of AAE against BrCa and potential for adjuvant to mTOR inhibition. PMID:25945840

  11. Polyphenol-rich extract of Pimenta dioica berries (Allspice) kills breast cancer cells by autophagy and delays growth of triple negative breast cancer in athymic mice.

    PubMed

    Zhang, Lei; Shamaladevi, Nagarajarao; Jayaprakasha, Guddadarangavvanahally K; Patil, Bhimu S; Lokeshwar, Bal L

    2015-06-30

    Bioactive compounds from edible plants have limited efficacy in treating advanced cancers, but they have potential to increase the efficacy of chemotherapy drugs in a combined treatment. An aqueous extract of berries of Pimenta dioica (Allspice) shows promise as one such candidate for combination therapy or chemoprevention. An aqueous extract of Allspice (AAE) was tested against human breast cancer (BrCa) cells in vitro and in vivo. AAE reduced the viability and clonogenic growth of several types of BrCa cells (IC50 ≤ 100 μg/ml) with limited toxicity in non-tumorigenic, quiescent cells (IC50 >200 μg/ml). AAE induced cytotoxicity in BrCa was inconsistent with apoptosis, but was associated with increased levels of autophagy markers LC3B and LC3B-positive puncta. Silencing the expression of autophagy related genes (ATGs) prevented AAE-induced cell death. Further, AAE caused inhibition of Akt/mTOR signaling, and showed enhanced cytotoxicity when combined with rapamycin, a chemotherapy drug and an inhibitor of mTOR signaling. Oral administration (gavage) of AAE into athymic mice implanted with MDA-MB231 tumors inhibited tumor growth slightly but not significantly (mean decrease ~ 14%, p ≥ 0.20) if mice were gavaged post-tumor implant. Tumor growth showed a significant delay (38%) in tumor palpability and growth rate (time to reach tumor volume ≥ 1,000 mm3) when mice were pre-dosed with AAE for two weeks. Analysis of tumor tissues showed increased levels of LC3B in AAE treated tumors, indicating elevated autophagic tumor cell death in vivo in treated mice. These results demonstrate antitumor and chemo-preventive activity of AAE against BrCa and potential for adjuvant to mTOR inhibition.

  12. Consumption of Pueraria flower extract reduces body mass index via a decrease in the visceral fat area in obese humans.

    PubMed

    Kamiya, Tomoyasu; Takano, Akira; Matsuzuka, Yuki; Kusaba, Nobutaka; Ikeguchi, Motoya; Takagaki, Kinya; Kondo, Kazuo

    2012-01-01

    In Japan, kudzu is a familiar plant, well-known as an ingredient in the Japanese-style confections kudzu-kiri and kudzu-mochi. In this study, we focused on the flower of kudzu (Pueraria thomsonii) and conducted a clinical trial to investigate the effects of Pueraria thomsonii flower extract (PFE) on obesity using obese Japanese males and females (BMI ≥ 25 kg/m(2)). Eighty-one obese subjects were randomly divided into three groups and consumed test food containing 300 mg of PFE, 200 mg of PFE, and a placebo over 12 weeks. The results indicate that PFE intake reduces BMI and decreases, the visceral fat area, but not the subcutaneous fat area. In addition, the decrease in visceral fat area showed no sexual dimorphism. Consequently, we propose that PFE intake expresses its BMI reduction effects via a decrease in visceral fat area.

  13. The nitrative and oxidative stress in blood platelets isolated from breast cancer patients: the protectory action of aronia melanocarpa extract.

    PubMed

    Kedzierska, Magdalena; Olas, Beata; Wachowicz, Barbara; Stochmal, Anna; Oleszek, Wieslaw; Jeziorski, Arkadiusz; Piekarski, Janusz

    2010-01-01

    Since mechanisms involved in the relationship between oxidative stress and breast cancer are still unclear, the aim of our present study was to evaluate oxidative/nitrative modifications of blood platelet proteins by measuring the level of biomarkers of oxidative/nitrative stress such as carbonyl groups, thiol groups and 3-nitrotyrosine in proteins in patients with benign breast diseases and in patients with invasive breast cancer, and compare with the control group. Levels of carbonyl groups and 3-nitrotyrosine residues in platelet proteins were measured by ELISA and a competition ELISA, respectively. The method with 5,5′-dithio-bis(2-nitro-benzoic acid) has been used to analyse free thiol groups in platelet proteins. Patients were hospitalized in the Department of Oncological Surgery, Medical University of Lodz, Poland. Exogenous antioxidants reduce oxidative stress, therefore we also investigated in a model system in vitro the effects of a polyphenol rich extract of Aronia melanocarpa (Rosaceae, final concentration of 50 µg/ml, 5 min, 37°C) on modified blood platelet proteins as well from patients with breast cancer and from the healthy group. We demonstrated in platelet proteins from patients with invasive breast cancer a higher level of carbonyl groups than in the control healthy group (p < 0.02). The level of 3-nitrotyrosine in platelet proteins from patients with invasive breast cancer was also significantly higher than in the healthy subject group (p < 0.001). In contrast, the amount of thiol groups in platelet proteins from patients was significantly lower (about < 50%) than in control blood platelets. In a model system in vitro we also observed that the extract from berries of A. melanocarpa (50 µg/ml, 5 min, 37°C) due to antioxidant action, significantly reduced the oxidative/nitrative stress (measured by thiol groups and 3-nitrotyrosine) in platelets, not only from the healthy group, but also from patients with benign breast diseases and in

  14. Brazilian propolis extract used as an additive to decrease methane emissions from the rumen microbial population in vitro.

    PubMed

    Santos, Nadine Woruby; Zeoula, Lucia Maria; Yoshimura, Emerson Henri; Machado, Erica; Macheboeuf, Didier; Cornu, Agnès

    2016-06-01

    Propolis is a product that is rich in phenolic compounds and can be utilized in animal nutrition as a dietary additive. In this study, the effects of a Brazilian green propolis extract on rumen fermentation and gas production were determined. The fate of propolis phenolic compounds in the rumen medium was also investigated. Fermentation was done in 24-h batches over three periods. Inoculates were obtained from cows fed on grassland hay and concentrate. Propolis extract in a hydroalcoholic solution was applied at increasing doses to the substrate (1 to 56 g/kg). The fermentation substrate consisted on a mixture of alfalfa hay, soybean meal, and wheat grain mixture in dry matter. After 24 h of fermentation, seven new compounds were observed in the medium in amounts that correlated to the propolis dose. The dose of propolis extract linearly decreased the pH of the medium and linearly increased propionate production, which reduced the acetate-to-propionate ratio and influenced the total production of short-chain fatty acids. Propolis also linearly reduced methane production and increased the carbon dioxide-to-methane ratio. Ammonia nitrogen levels and in vitro digestibility of organic matter were similar among the treatments. The combination of increased propionate production and decreased methane production suggests better energy utilization from the feed.

  15. Pitaya Extracts Induce Growth Inhibition and Proapoptotic Effects on Human Cell Lines of Breast Cancer via Downregulation of Estrogen Receptor Gene Expression.

    PubMed

    Guimarães, Deborah de Almeida Bauer; De Castro, Danielle Dos Santos Bonfim; de Oliveira, Felipe Leite; Nogueira, Eduardo Matos; da Silva, Marco Antônio Mota; Teodoro, Anderson Junger

    2017-01-01

    Breast cancer is one of the most prevalent cancers in the world and is also the leading cause of cancer death in women. The use of bioactive compounds of functional foods contributes to reduce the risk of chronic diseases, such as cancer and vascular disorders. In this study, we evaluated the antioxidant potential and the influence of pitaya extract (PE) on cell viability, colony formation, cell cycle, apoptosis, and expression of BRCA1, BRCA2, PRAB, and Erα in breast cancer cell lines (MCF-7 and MDA-MB-435). PE showed high antioxidant activity and high values of anthocyanins (74.65 ± 2.18). We observed a selective decrease in cell proliferation caused by PE in MCF-7 (ER(+)) cell line. Cell cycle analysis revealed that PE induced an increase in G0/G1 phase followed by a decrease in G2/M phase. Also, PE induced apoptosis in MCF-7 (ER(+)) cell line and suppressed BRCA1, BRCA2, PRAB, and Erα gene expression. Finally, we also demonstrate that no effect was observed with MDA-MB-435 cells (ER(-)) after PE treatment. Taken together, the present study suggests that pitaya may have a protective effect against breast cancer.

  16. Pitaya Extracts Induce Growth Inhibition and Proapoptotic Effects on Human Cell Lines of Breast Cancer via Downregulation of Estrogen Receptor Gene Expression

    PubMed Central

    De Castro, Danielle dos Santos Bonfim; de Oliveira, Felipe Leite; Nogueira, Eduardo Matos; da Silva, Marco Antônio Mota

    2017-01-01

    Breast cancer is one of the most prevalent cancers in the world and is also the leading cause of cancer death in women. The use of bioactive compounds of functional foods contributes to reduce the risk of chronic diseases, such as cancer and vascular disorders. In this study, we evaluated the antioxidant potential and the influence of pitaya extract (PE) on cell viability, colony formation, cell cycle, apoptosis, and expression of BRCA1, BRCA2, PRAB, and Erα in breast cancer cell lines (MCF-7 and MDA-MB-435). PE showed high antioxidant activity and high values of anthocyanins (74.65 ± 2.18). We observed a selective decrease in cell proliferation caused by PE in MCF-7 (ER+) cell line. Cell cycle analysis revealed that PE induced an increase in G0/G1 phase followed by a decrease in G2/M phase. Also, PE induced apoptosis in MCF-7 (ER+) cell line and suppressed BRCA1, BRCA2, PRAB, and Erα gene expression. Finally, we also demonstrate that no effect was observed with MDA-MB-435 cells (ER−) after PE treatment. Taken together, the present study suggests that pitaya may have a protective effect against breast cancer. PMID:28761624

  17. Decreased expression of alpha-2-HS glycoprotein in the sera of rats treated with Eurycoma longifolia extract.

    PubMed

    Chen, Yeng; Phang, Wai-Mei; Mu, Alan K-W; Chan, Choon-Keat; Low, Bin-Seng; Sasidharan, Sreenivasan; Chan, Kit-Lam

    2015-01-01

    Eurycoma longifolia is a Malaysian native herb that has been widely used as an aphrodisiac and a remedy for andropause. Although the physiological effects of the plant extract were predicted as a result of the alterations in protein expression, the key protein(s) involved in these alterations are still unclear. In the present study, we have investigated the effect of standardized E. longifolia extract on serum protein expression up to 28 days following oral administration in rats. Serum protein profiles were analyzed by 2-dimensional electrophoresis, and altered proteins were identified via mass spectrometry. We observed that alpha-2-HS glycoprotein (AHS) was significantly decreased in the serum of experimentally treated rats compared to pre-treated animals. Moreover, reduction in AHS was confirmed using competitive enzyme-linked immunosorbent assay. AHS expression is known to be associated with insulin resistance and diabetes. Our data indicated that serum AHS was reduced in rats treated with standardized E. longifolia extract, and therefore form a prelude for further investigation into the effects of this natural extract in animal models involving infertility and diabetes.

  18. Decreased expression of alpha-2-HS glycoprotein in the sera of rats treated with Eurycoma longifolia extract

    PubMed Central

    Chen, Yeng; Phang, Wai-Mei; Mu, Alan K.-W.; Chan, Choon-Keat; Low, Bin-Seng; Sasidharan, Sreenivasan; Chan, Kit-Lam

    2015-01-01

    Eurycoma longifolia is a Malaysian native herb that has been widely used as an aphrodisiac and a remedy for andropause. Although the physiological effects of the plant extract were predicted as a result of the alterations in protein expression, the key protein(s) involved in these alterations are still unclear. In the present study, we have investigated the effect of standardized E. longifolia extract on serum protein expression up to 28 days following oral administration in rats. Serum protein profiles were analyzed by 2-dimensional electrophoresis, and altered proteins were identified via mass spectrometry. We observed that alpha-2-HS glycoprotein (AHS) was significantly decreased in the serum of experimentally treated rats compared to pre-treated animals. Moreover, reduction in AHS was confirmed using competitive enzyme-linked immunosorbent assay. AHS expression is known to be associated with insulin resistance and diabetes. Our data indicated that serum AHS was reduced in rats treated with standardized E. longifolia extract, and therefore form a prelude for further investigation into the effects of this natural extract in animal models involving infertility and diabetes. PMID:26441666

  19. [Decrease in toxicity and therapeutic effect of zoledronic acid in combination therapy with different antioxidant extracts].

    PubMed

    Lopez-Morata, José Antonio; Olivares, Amparo; Alcaraz, Miguel

    Zoledronic acid is used in the treatment of cancer-related diseases, although its use has been associated with avascular osteonecrosis. To determine the possible protective effect of a range of antioxidant substances against the inhibition of human prostate epithelial cell growth (PNT2) and transgenic adenocarcinoma mouse prostate tumour cells (TRAMP-C1), in treatments combining zoledronic acid and ionising radiation (IR). Cell survival is studied via cell viability assays (MTT) for 2 cell lines in isolated and combined treatments with zoledronic acid and/or IR, as well as the effect of adding 3 antioxidant substances. Zoledronic acid displays a significant cytotoxic effect over PNT2 and TRAMP-C1 cells (P<.001). The administration of antioxidants together with the zoledronic acid shows a protective effect for normal prostate cells, yet not so for prostate tumour cells. However, the administration of rosmarinic acid and apigenin in treatments combined with zoledronic acid provides a protective effect from the harmful effects of applying ionizing radiation, not only for normal PNT2 cells, but also for tumour cells. The use of antioxidant substances decreases the cytotoxic effect of zoledronic acid over non-tumour cells, and as such could be used in benign diseases. Furthermore, in the combined treatment using ionising radiation, these antioxidants also produced a protective effect in tumour cells, thus reducing the therapeutic effect sought by combining the treatment with radiation. Copyright © 2016 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

    PubMed Central

    Dharsee, Moyez; Tran-Thanh, Danh; Ackloo, Suzanne; Zhu, Pei Hong; Sardana, Girish; Chen, Jian; Kupchak, Peter; Jacks, Lindsay M.; Miller, Naomi A.; Youngson, Bruce J.; Iakovlev, Vladimir; Guidos, Cynthia J.; Vallis, Katherine A.; Evans, Kenneth R.; McCready, David; Leong, Wey L.; Done, Susan J.

    2012-01-01

    Background Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays. Methods and Findings Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment. Conclusions Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features. PMID:22363530

  1. Decreased expression of miR-204 is associated with poor prognosis in patients with breast cancer.

    PubMed

    Li, Weidong; Jin, Xuejun; Zhang, Qianbing; Zhang, Gong; Deng, Xubin; Ma, Lei

    2014-01-01

    The identification of biomarkers in breast cancer diagnosis and therapy is important in achieving early cancer diagnosis and improving patient outcomes. The aim of this study was to examine clinical significance of miR-204 expression in tissues from breast cancer patients. The relationship between miR-204 expression and clinicopathological characteristics was investigated. MiR-204 expression was significantly associated with TNM stage and metastasis. Patients with low miR-204 expression had poorer overall survival time and disease free survival time than those with high miR-204 expression. Furthermore, miR-204 expression was correlated with chemotherapeutic resistance of breast cancer patients. In conclusion, the miR-204 may be a potential diagnostic and prognostic biomarker of breast cancer.

  2. Effect of plant extracts on physicochemical properties of chicken breast meat cooked using conventional electric oven or microwave.

    PubMed

    Rababah, T M; Ereifej, K I; Al-Mahasneh, M A; Al-Rababah, M A

    2006-01-01

    This study evaluated effects of vacuum-infused fresh chicken breast meats with grape seed extracts, green tea extracts, or tertiary butyl hydroquinone on pH, texture, color, and thiobarbituric reactive substances after cooking using a microwave or conventional electric oven for 12 d storage at 5 degrees C. Thiobarbituric reactive substances values of uncooked (raw) chicken breast meats for 0 to 12 d of storage ranged from 1.12 to 3.5 mg of malonaldehyde/100 g of chicken. During 0 to 12 d of storage, thiobarbituric reactive substances values ranged from 2.50 to 7.80 and from 2.4 to 7.35 mg of malonaldehyde/100 g of chicken breast meat cooked by microwave and conventional electric oven, respectively. Meats cooked by microwave had higher redness and lower lightness values than those cooked by conventional electric oven. Also, meats cooked by microwave had higher maximum shear force, working of shear, hardness, springiness, cohesiveness, and chewiness values than meats cooked by conventional electric oven. Tertiary butyl hydroquinone was the most effective in raw and cooked meats in reducing lipid oxidation, followed by grape seed and green tea extracts. Plant extracts are effective in preventing undesirable changes in chemical properties in chicken breast meat caused by microwave and conventional electric oven cooking.

  3. ANTIPROLIFERATIVE EFFECT ON BREAST CANCER (MCF7) OF MORINGA OLEIFERA SEED EXTRACTS.

    PubMed

    Adebayo, Ismail Abiola; Arsad, Hasni; Samian, Mohd Razip

    2017-01-01

    Moringa oleifera belongs to plant family, Moringaceae and popularly called "wonderful tree", for it is used traditionally to cure many diseases including cancer in Africa and Asia, however, there is limited knowledge on cytotoxic activity of Moringa oleifera seeds on MCF7 breast cancer cell. The present study evaluated antiproliferative effect on MCF7 of the seed. Seeds of Moringa oleifera were grinded to powder and its phytochemicals were extracted using water and 80% ethanol solvents, part of the ethanolic extract were sequentially partitioned to fractions with four solvents (hexane, dichloromethane, chloroform, and n-butanol). Antiproliferative effects on MCF7 of the samples were determined. Finally, potent samples that significantly inhibited MCF7 growth were tested on MCF 10A. Crude water extract, hexane and dichloromethane fractions of the seeds inhibited the proliferation of MCF7 with the following IC50 values 280 μg/ml, 130 μg/ml and 26 μg/ml respectively, however, of the 3 samples, only hexane fraction had minimal cytotoxic effect on MCF 10A (IC50 > 400μg/ml). Moringa oleifera seed has antiproliferative effect on MCF7.

  4. ANTIPROLIFERATIVE EFFECT ON BREAST CANCER (MCF7) OF MORINGA OLEIFERA SEED EXTRACTS

    PubMed Central

    Adebayo, Ismail Abiola; Arsad, Hasni; Samian, Mohd Razip

    2017-01-01

    Background: Moringa oleifera belongs to plant family, Moringaceae and popularly called “wonderful tree”, for it is used traditionally to cure many diseases including cancer in Africa and Asia, however, there is limited knowledge on cytotoxic activity of Moringa oleifera seeds on MCF7 breast cancer cell. The present study evaluated antiproliferative effect on MCF7 of the seed. Materials and Methods: Seeds of Moringa oleifera were grinded to powder and its phytochemicals were extracted using water and 80% ethanol solvents, part of the ethanolic extract were sequentially partitioned to fractions with four solvents (hexane, dichloromethane, chloroform, and n-butanol). Antiproliferative effects on MCF7 of the samples were determined. Finally, potent samples that significantly inhibited MCF7 growth were tested on MCF 10A. Results: Crude water extract, hexane and dichloromethane fractions of the seeds inhibited the proliferation of MCF7 with the following IC50 values 280 μg/ml, 130 μg/ml and 26 μg/ml respectively, however, of the 3 samples, only hexane fraction had minimal cytotoxic effect on MCF 10A (IC50 > 400μg/ml). Conclusion: Moringa oleifera seed has antiproliferative effect on MCF7. PMID:28573245

  5. Differential metabolomic analysis of the potential antiproliferative mechanism of olive leaf extract on the JIMT-1 breast cancer cell line.

    PubMed

    Barrajón-Catalán, Enrique; Taamalli, Amani; Quirantes-Piné, Rosa; Roldan-Segura, Cristina; Arráez-Román, David; Segura-Carretero, Antonio; Micol, Vicente; Zarrouk, Mokhtar

    2015-02-01

    A new differential metabolomic approach has been developed to identify the phenolic cellular metabolites derived from breast cancer cells treated with a supercritical fluid extracted (SFE) olive leaf extract. The SFE extract was previously shown to have significant antiproliferative activity relative to several other olive leaf extracts examined in the same model. Upon SFE extract incubation of JIMT-1 human breast cancer cells, major metabolites were identified by using HPLC coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry (ESI-Q-TOF-MS). After treatment, diosmetin was the most abundant intracellular metabolite, and it was accompanied by minor quantities of apigenin and luteolin. To identify the putative antiproliferative mechanism, the major metabolites and the complete extract were assayed for cell cycle, MAPK and PI3K proliferation pathways modulation. Incubation with only luteolin showed a significant effect in cell survival. Luteolin induced apoptosis, whereas the whole olive leaf extract incubation led to a significant cell cycle arrest at the G1 phase. The antiproliferative activity of both pure luteolin and olive leaf extract was mediated by the inactivation of the MAPK-proliferation pathway at the extracellular signal-related kinase (ERK1/2). However, the flavone concentration of the olive leaf extract did not fully explain the strong antiproliferative activity of the extract. Therefore, the effects of other compounds in the extract, probably at the membrane level, must be considered. The potential synergistic effects of the extract also deserve further attention. Our differential metabolomics approach identified the putative intracellular metabolites from a botanical extract that have antiproliferative effects, and this metabolomics approach can be expanded to other herbal extracts or pharmacological complex mixtures.

  6. Decreased FOXF2 mRNA expression indicates early-onset metastasis and poor prognosis for breast cancer patients with histological grade II tumor.

    PubMed

    Kong, Peng-Zhou; Yang, Fan; Li, Lin; Li, Xiao-Qing; Feng, Yu-Mei

    2013-01-01

    The transcription factor, FOXF2, plays an important role in tissue development, extracellular matrix synthesis, and epithelial-mesenchymal interactions, implying that it may be associated with the metastatic capabilities of cancer cells. However, the relationship between FOXF2 expression and breast cancer progression, metastasis, and prognosis, remains to be elucidated. In this study, FOXF2 mRNA levels in 305 primary breast cancer tissues were examined using RT-QPCR. Results showed that FOXF2 mRNA levels in primary breast cancer were negatively associated with tumor progression, including tumor size, number of metastatic lymph nodes, and clinical stage. Patients with low FOXF2 mRNA levels had a high risk of relapse and metastasis within three years. Low FOXF2 mRNA levels could predict shorter disease-free survival for those patients with histological grade II and triple-negative breast cancer. Taken together, we conclude that decreased FOXF2 expression indicates the early-onset metastasis and poor prognosis for patients with histological grade II and triple-negative breast cancer.

  7. Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer

    PubMed Central

    Liao, X-H; Wang, J-G; Li, L-Y; Zhou, D-M; Ren, K-H; Jin, Y-T; Lv, L; Yu, J-G; Yang, J-Y; Lu, Q; Zou, Q; Yu, J; Liu, X-P; Zhou, P

    2016-01-01

    Increasing evidence indicates that long non-coding RNAs (lncRNAs) act as important regulatory factors in tumor progression. However, their roles in breast cancer remain largely unknown. In present studies, we identified aberrantly expressed long intergenic non-coding RNA APOC1P1-3 (lincRNA-APOC1P1-3) in breast cancer by microarray, verified it by quantitative real-time PCR, and assessed methylation status in the promoter region by pyrosequencing. We also investigated the biological functions with plasmid transfection and siRNA silencing experiments, and further explored their mechanisms by RNA pull-down and RNA immunoprecipitation to identify binding proteins. We found that 224 lncRNAs were upregulated in breast cancer, whereas 324 were downregulated. The lincRNA-APOC1P1-3 was overexpressed in breast cancer, which was related to tumor size and hypomethylation in its promoter region. We also found that APOC1P1-3 could directly bind to tubulin to decrease α-tubulin acetylation, to inactivate caspase-3, and to inhibit apoptosis. This study demonstrates that overexpression of APOC1P1-3 can inhibit breast cancer apoptosis. PMID:27228351

  8. Alkaloids extracted from Pterogyne nitens induce apoptosis in malignant breast cell line.

    PubMed

    Duarte, Roberta Aparecida; Mello, Elaine Rodrigues; Araki, Camila; Bolzani, Vanderlan da Silva; Siqueira e Silva, Dulce Helena; Regasini, Luis Octavio; Silva, Tarsia Giabardo Alves; de Morais, Mauro César Cafundó; Ximenes, Valdecir Farias; Soares, Christiane Pienna

    2010-10-01

    In the present study, two alkaloids isolated from Pterogyne nitens, a plant native to Brazil, have been shown to induce apoptosis in human breast cancer cells. These compounds, pterogynine (PGN) and pterogynidine (PGD), were tested for their effect on a human infiltrating ductal carcinoma cell line (ZR-7531). The cell line was treated with each alkaloid at several concentrations. Time-dependence (with or without recuperation time) and concentration-dependence (in the range 0.25-10 mM) were investigated in cytotoxicity and apoptosis assays. The annexin assay indicated an apparently higher percentage of death by necrosis of malignant cells after 24 h exposure to both P. nitens extracts than the Hoechst assay. Thus, our results in the two tests demonstrated that the Hoechst assay can discriminate between late apoptotic cells and necrosis, whereas the flow cytometry-based annexin V assay cannot. We concluded that PGN and PGD have effective antineoplastic activity against human breast cancer cells in vitro, by inducing programmed cell death.

  9. Effect of black raspberry extract in inhibiting NFkappa B dependent radioprotection in human breast cancer cells.

    PubMed

    Madhusoodhanan, Rakhesh; Natarajan, Mohan; Singh, Jamunarani Veeraraghavan Nisha; Jamgade, Ambarish; Awasthi, Vibhudutta; Anant, Shrikant; Herman, Terence S; Aravindan, Natarajan

    2010-01-01

    Black raspberry extracts (RSE) have been shown to inhibit cancer cell growth and stimulate apoptosis. Also, studies have demonstrated that RSE inhibits transcriptional regulators including NFkappa B. Accordingly, we investigated the effect of RSE in inhibiting radiation (IR) induced NFkappa B mediated radioprotection in breast adenocarcinoma cells. MCF-7 cells were exposed to IR (2Gy), treated with RSE (0.5, 1.0, 2.0 micro g/ml) or treated with RSE (1.0 micro g/ml) followed by IR exposure, and harvested after 1, 3, 6, 24, 48, and 72 h. NFkappa B DNA-binding activity was measured by EMSA and phosphorylated Ikappa Balpha by immunoblotting. Expression of IAP1, IAP2, XIAP and survivin were measured by QPCR and immunoblotting. Cell survival was measured using MTT assay and cell death using Caspase-3/7 activity. Effect of RSE on IR induced MnSOD, TNFalpha, IL-1alpha and MnSOD activity was also determined. RSE inhibited NFkappa B activity in a dose-dependent manner. Also, RSE inhibited IR-induced sustained activation of NFkappa B, and NFkappa B regulated IAP1, IAP2, XIAP, and survivin. In addition, RSE inhibited IR-induced TNFalpha, IL-1alpha, and MnSOD levels and MnSOD activity. RSE suppressed cell survival and enhanced cell death. These results suggest that RSE may act as a potent radiosensitizer by overcoming the effects of NFkappa B mediated radioprotection in human breast cancer cells.

  10. Water extract of Rheum officinale Baill. induces apoptosis in human lung adenocarcinoma A549 and human breast cancer MCF-7 cell lines.

    PubMed

    Li, Wing-Yan; Chan, Shun-Wan; Guo, De-Jian; Chung, Mei-Kuen; Leung, Tin-Yan; Yu, Peter Hoi-Fu

    2009-07-15

    Rheum officinale Baill. (Da Huang) is one of the herbs commonly used in traditional Chinese medicine formulae against cancer. The traditional decoction is similar to the water extract used in the present study. The water extract of Da Huang was investigated to see if it possesses anticancer effects through apoptotic pathways. Human lung adenocarcinoma A549 and human breast cancer MCF-7 cell lines were treated with different concentrations of Da Huang water extract at different time intervals. Growth inhibition was detected by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] and colony formation assays; apoptosis was detected by cell morphologic analysis, DNA fragmentation analysis and COMET assay. Da Huang water extract was found to have significant growth inhibitory effects on both A549 and MCF-7 cell lines with IC(50) values 620+/-12.7 and 515+/-10.1 microg/ml, respectively. Growth inhibitory effects were dose- and time-dependent. A significant decrease in cell number, DNA fragmentation and single DNA strand breakages were observed in the Da Huang water extract treated A549 and MCF-7 cells. This suggests that the water extract of Da Huang exerts potential anticancer activity through growth inhibition and apoptosis on MCF-7 and A549 cells lines.

  11. Antiproliferative and Proapoptotic Activities of Marine Sponge Hyrtios erectus Extract on Breast Carcinoma Cell Line (MCF-7)

    PubMed Central

    Muthiyan, Ramachandran; Nambikkairaj, Balwin; Mahanta, Nilkamal; Immanuel, Titus; Mandal, Rahul Shubhra; Kumaran, Kubendiran; De, Arun Kumar

    2017-01-01

    Background: Marine sponge is a rich natural resource of many pharmacologically important compounds. Objective: Marine sponge Hyrtios erectus, collected from North Bay, South Andaman Sea, India, was screened for potential antiproliferative and proapoptotic properties on a breast adenocarcinoma cell line (MCF-7). Materials and Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to test the antiproliferative and cytotoxicity effects of the sponge extract. Analysis of apoptosis and cell cycle stages were done by flow cytometry. The expression of several apoptotic-related proteins in MCF-7 cells treated by the extract was evaluated by Western blot analysis. Various analytical techniques including Fourier transform infrared spectroscopy, gas chromatography-mass spectrometry, and nuclear magnetic resonance were employed to determine the identity of the active compounds in the sponge extract. Results: N-Hexane extract of the sponge inhibited proliferation of the MCF-7 cell line in a dose- and time-dependent manner. Exposure of the sponge extract triggered apoptosis of the MCF-7 cells, induced DNA fragmentation, and arrested the cells in G2/M phase. Treatment of the sponge extract induced downregulation of antiapoptotic Bcl-2 protein and upregulation of Bax, caspase-3, caspase-9, and fragmented poly(ADP ribose)polymerase proteins in MCF-7 cells. Five bioactive compounds have been identified in the extract. Conclusion: The antiproliferative and proapoptotic activities of the tested extract suggested the pharmacologic potential of the identified compounds. Further characterization of the identified compounds are in progress. SUMMARY The N-hexane extract of the marine sponge Hyrtios erectus, collected from North Bay, South Andaman Sea, India, showed potential antiproliferative and proapoptotic properties against a breast adenocarcinoma cell line (MCF-7).The sponge extract retarded the growth of breast carcinoma cell line MCF-7 cells in a time

  12. Effects of Thymus serpyllum extract on cell proliferation, apoptosis and epigenetic events in human breast cancer cells.

    PubMed

    Bozkurt, Emir; Atmaca, Harika; Kisim, Asli; Uzunoglu, Selim; Uslu, Ruchan; Karaca, Burcak

    2012-01-01

    Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment.

  13. Beneficial effects of a medicinal herb, Cirsium japonicum var. maackii, extract and its major component, cirsimaritin on breast cancer metastasis in MDA-MB-231 breast cancer cells.

    PubMed

    Yeon Park, Jun; Young Kim, Hyun; Shibamoto, Takayuki; Su Jang, Tae; Cheon Lee, Sang; Suk Shim, Jae; Hahm, Dae-Hyun; Lee, Hae-Jeung; Lee, Sanghyun; Sung Kang, Ki

    2017-09-01

    The biological activities of the ethanol extract from Cirsium japonicum var. maackii (ICF-1) and its major component, polyphenol cirsimaritin, were investigated as part of the search for possible alternative drugs for breast cancer. Three in vitro cell-based assays were used: the cell proliferation assay, tube-formation assay, and Western blot analysis. Both the ICF-1 extract and cirsimaritin inhibited the viability of HUVECs in a dose-dependent manner. The inhibition achieved was 36.89% at a level of 200μg/ml by the ICF-1 extract and 62.04% at a level of 100μM by cirsimaritin. The ICF-1 extract and cirsimaritin reduced tube formation by 12.69% at level of 25μg/ml and 32.18% at the levels of 6.25μM, respectively. Cirsimaritin inhibited angiogenesis by downregulation of VEGF, p-Akt and p-ERK in MDA-MB-231 cells, suggesting that cirsimaritin is potentially useful as an anti-metastatic agent. The present study demonstrated that Cirsium japonicum extract and its active component cirsimaritin is an excellent candidate as an alternative anti-breast cancer drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Anticancer activity of Petroselinum sativum seed extracts on MCF-7 human breast cancer cells.

    PubMed

    Farshori, Nida Nayyar; Al-Sheddi, Ebtesam Saad; Al-Oqail, Mai Mohammad; Musarrat, Javed; Al-Khedhairy, Abdulaziz Ali; Siddiqui, Maqsood Ahmed

    2013-01-01

    Pharmacological and preventive properties of Petroselinum sativum seed extracts are well known, but the anticancer activity of alcoholic extracts and oil of Petroselinum sativum seeds on human breast cancer cells have not been explored so far. Therefore, the present study was designed to investigate the cytotoxic activities of these extracts against MCF-7 cells. Cells were exposed to 10 to 1000 μg/ml of alcoholic seed extract (PSA) and seed oil (PSO) of Petroselinum sativum for 24 h. Post-treatment, percent cell viability was studied by 3-(4, 5-dimethylthiazol-2yl)-2, 5-biphenyl tetrazolium bromide (MTT) and neutral red uptake (NRU) assays, and cellular morphology by phase contrast inverted microscopy. The results showed that PSA and PSO significantly reduced cell viability, and altered the cellular morphology of MCF-7 cells in a concentration dependent manner. Concentrations of 50 μg/ml and above of PSA and 100 μg/ml and above of PSO were found to be cytotoxic in MCF-7 cells. Cell viability at 50, 100, 250, 500 and 1000 μg/ml of PSA was recorded as 81%, 57%, 33%, 8% and 5%, respectively, whereas at 100, 250, 500, and 1000 μg/ml of PSO values were 90%, 78%, 62%, and 8%, respectively by MTT assay. MCF-7 cells exposed to 250, 500 and 1000 μg/ml of PSA and PSO lost their typical morphology and appeared smaller in size. The data revealed that the treatment with PSA and PSO of Petroselinum sativum induced cell death in MCF-7 cells.

  15. It is out of my hands: how deferring control to God can decrease quality of life for breast cancer patients.

    PubMed

    McLaughlin, Bryan; Yoo, Woohyun; D'Angelo, Jonathan; Tsang, Stephanie; Shaw, Bret; Shah, Dhavan; Baker, Timothy; Gustafson, David

    2013-12-01

    This paper seeks to contribute to the understanding of how and why religion affects psychosocial health outcomes. We propose a theoretical model predicting that when women with breast cancer defer control to God they will experience fewer breast cancer related concerns. Deferring control to God, however, should also reduce the likelihood that they take a proactive coping approach, which will be exacerbated by lowered breast cancer concerns. We therefore predict that this passive coping style will ultimately result in lower levels of quality of life. Data were collected as part of a randomized clinical trial funded by the National Cancer Institute. A total of 192 women with breast cancer participated in a computer-mediated social support group. Deferring control to God statements were captured by using computer-aided content analysis of discussion posts. Psychosocial outcomes were measured using longitudinal survey data. Analysis was performed using structural equation modeling. The results of our analysis largely confirm our mediation model for which we find significant model fit. As predicted, deferring control to God leads to lower levels of breast cancer concerns but also to more passive coping styles. Ultimately, deferring control to God can lead to lower levels of quality of life. Our study demonstrates how and why religious coping can lead to both positive and negative psychosocial health outcomes. Health care practitioners should encourage patients who are relying on religion to keep their end of the bargain and maintain an active coping style. Copyright © 2013 John Wiley & Sons, Ltd.

  16. Evaluation of an Automated Information Extraction Tool for Imaging Data Elements to Populate a Breast Cancer Screening Registry.

    PubMed

    Lacson, Ronilda; Harris, Kimberly; Brawarsky, Phyllis; Tosteson, Tor D; Onega, Tracy; Tosteson, Anna N A; Kaye, Abby; Gonzalez, Irina; Birdwell, Robyn; Haas, Jennifer S

    2015-10-01

    Breast cancer screening is central to early breast cancer detection. Identifying and monitoring process measures for screening is a focus of the National Cancer Institute's Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) initiative, which requires participating centers to report structured data across the cancer screening continuum. We evaluate the accuracy of automated information extraction of imaging findings from radiology reports, which are available as unstructured text. We present prevalence estimates of imaging findings for breast imaging received by women who obtained care in a primary care network participating in PROSPR (n = 139,953 radiology reports) and compared automatically extracted data elements to a "gold standard" based on manual review for a validation sample of 941 randomly selected radiology reports, including mammograms, digital breast tomosynthesis, ultrasound, and magnetic resonance imaging (MRI). The prevalence of imaging findings vary by data element and modality (e.g., suspicious calcification noted in 2.6% of screening mammograms, 12.1% of diagnostic mammograms, and 9.4% of tomosynthesis exams). In the validation sample, the accuracy of identifying imaging findings, including suspicious calcifications, masses, and architectural distortion (on mammogram and tomosynthesis); masses, cysts, non-mass enhancement, and enhancing foci (on MRI); and masses and cysts (on ultrasound), range from 0.8 to1.0 for recall, precision, and F-measure. Information extraction tools can be used for accurate documentation of imaging findings as structured data elements from text reports for a variety of breast imaging modalities. These data can be used to populate screening registries to help elucidate more effective breast cancer screening processes.

  17. [Feature extraction for breast cancer data based on geometric algebra theory and feature selection using differential evolution].

    PubMed

    Li, Jing; Hong, Wenxue

    2014-12-01

    The feature extraction and feature selection are the important issues in pattern recognition. Based on the geometric algebra representation of vector, a new feature extraction method using blade coefficient of geometric algebra was proposed in this study. At the same time, an improved differential evolution (DE) feature selection method was proposed to solve the elevated high dimension issue. The simple linear discriminant analysis was used as the classifier. The result of the 10-fold cross-validation (10 CV) classification of public breast cancer biomedical dataset was more than 96% and proved superior to that of the original features and traditional feature extraction method.

  18. Rice bran extract containing acylated steryl glucoside fraction decreases elevated blood LDL cholesterol level in obese Japanese men.

    PubMed

    Ito, Yukihiko; Nakashima, Yuri; Matsuoka, Sayuri

    2015-01-01

    People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.

  19. Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells.

    PubMed

    Burton, Liza J; Smith, Basil A; Smith, Bethany N; Loyd, Quentin; Nagappan, Peri; McKeithen, Danielle; Wilder, Catera L; Platt, Manu O; Hudson, Tamaro; Odero-Marah, Valerie A

    2015-09-01

    To develop new and effective chemopreventive agents against bone metastasis, we assessed the effects of muscadine grape skin extract (MSKE), whose main bioactive component is anthocyanin, on bone turnover, using prostate and breast cancer cell models overexpressing Snail transcription factor. MSKE has been shown previously to promote apoptosis in prostate cancer cells without affecting normal prostate epithelial cells. Snail is overexpressed in prostate and breast cancer, and is associated with increased invasion, migration and bone turnover/osteoclastogenesis. Cathepsin L (CatL) is a cysteine cathepsin protease that is overexpressed in cancer and involved in bone turnover. Snail overexpression in prostate (LNCaP, ARCaP-E) and breast (MCF-7) cancer cells led to increased CatL expression/activity and phosphorylated STAT-3 (pSTAT-3), compared to Neo vector controls, while the reverse was observed in C4-2 (the aggressive subline of LNCaP) cells with Snail knockdown. Moreover, CatL expression was higher in prostate and breast tumor tissue compared to normal tissue. MSKE decreased Snail and pSTAT3 expression, and abrogated Snail-mediated CatL activity, migration and invasion. Additionally, Snail overexpression promoted osteoclastogenesis, which was significantly inhibited by the MSKE as effectively as Z-FY-CHO, a CatL-specific inhibitor, or osteoprotegerin, a receptor activator of nuclear factor kappa B ligand (RANKL) antagonist. Overall, these novel findings suggest that Snail regulation of CatL may occur via STAT-3 signaling and can be antagonized by MSKE, leading to decreased cell invasion, migration and bone turnover. Therefore, inhibition using a natural product such as MSKE could potentially be a promising bioactive compound for bone metastatic cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Muscadine grape skin extract can antagonize Snail-cathepsin L-mediated invasion, migration and osteoclastogenesis in prostate and breast cancer cells

    PubMed Central

    Burton, Liza J.; Smith, Basil A.; Smith, Bethany N.; Loyd, Quentin; Nagappan, Peri; McKeithen, Danielle; Wilder, Catera L.; Platt, Manu O.; Hudson, Tamaro

    2015-01-01

    To develop new and effective chemopreventive agents against bone metastasis, we assessed the effects of muscadine grape skin extract (MSKE), whose main bioactive component is anthocyanin, on bone turnover, using prostate and breast cancer cell models overexpressing Snail transcription factor. MSKE has been shown previously to promote apoptosis in prostate cancer cells without affecting normal prostate epithelial cells. Snail is overexpressed in prostate and breast cancer, and is associated with increased invasion, migration and bone turnover/osteoclastogenesis. Cathepsin L (CatL) is a cysteine cathepsin protease that is overexpressed in cancer and involved in bone turnover. Snail overexpression in prostate (LNCaP, ARCaP-E) and breast (MCF-7) cancer cells led to increased CatL expression/activity and phosphorylated STAT-3 (pSTAT-3), compared to Neo vector controls, while the reverse was observed in C4-2 (the aggressive subline of LNCaP) cells with Snail knockdown. Moreover, CatL expression was higher in prostate and breast tumor tissue compared to normal tissue. MSKE decreased Snail and pSTAT3 expression, and abrogated Snail-mediated CatL activity, migration and invasion. Additionally, Snail overexpression promoted osteoclastogenesis, which was significantly inhibited by the MSKE as effectively as Z-FY-CHO, a CatL-specific inhibitor, or osteoprotegerin, a receptor activator of nuclear factor kappa B ligand (RANKL) antagonist. Overall, these novel findings suggest that Snail regulation of CatL may occur via STAT-3 signaling and can be antagonized by MSKE, leading to decreased cell invasion, migration and bone turnover. Therefore, inhibition using a natural product such as MSKE could potentially be a promising bioactive compound for bone metastatic cancer. PMID:26069256

  1. Green coffee bean extract improves obesity by decreasing body fat in high-fat diet-induced obese mice.

    PubMed

    Choi, Bong-Keun; Park, Sung-Bum; Lee, Dong-Ryung; Lee, Hae Jin; Jin, Ying-Yu; Yang, Seung Hwan; Suh, Joo-Won

    2016-07-01

    To evaluate possible lipid catabolism and body fat regulation effects of 3-caffeoylquinic acid in Green coffee bean extract (GCBE) in high-fat diet (HFD)-induced obese mice. Obesity was induced in mice using a HFD for four weeks. Then, mice were fed only HFD or HFD with GCBE at 50, 100, and 200 mg/kg. Fatty acid synthesis mechanism regulation of body fat was investigated through real-time PCR and Western blot assay. Body fat reduction was measured through dual-energy X-ray absorptiometry. In HFD-induced obese mice, GCBE treatment significantly decreased body weight gain, liver weight and white adipose tissue weights with regulation of adipose tissue lipolysis hormones, like adiponectin and leptin. GCBE treatment decreased mRNA expression levels of adipogenesis and adipocyte metabolism related genes in adipose tissues and the liver, and decreased the corresponding protein expression. Dual energy X-ray absorptiometry measurements were used to compare body fat between mice on high-fat and those treated with GCBE. GCBE treated mice had a lower fat mass compared to HFD alone fed mice and relative body weight and fat mass were markedly decreased. GCBE has a potential anti-obesity effect with lowering body fat accumulation by regulating adipogenesis and lipid metabolism-related genes and proteins in WAT and liver. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

  2. Chemotherapeutic Vulnerability of Triple-negative Breast Cancer Cell-derived Tumors to Pretreatment with Vernonia amygdalina Aqueous Extracts

    PubMed Central

    Howard, Carolyn B.; Mcdowell, Roderick; Feleke, Kidus; Deer, Evangeline; Stamps, Symone; Thames, Easter; Singh, Vikash; Pervin, Shehla

    2016-01-01

    Background Unresponsive to most clinical therapies, triple-negative breast cancer (TNBC) is the dominant biological cause of population-based racioethnic disparities in breast cancer mortality in the United States. We report the chemotherapeutic vulnerability of TNBC cells and stem cell-derived tumors to Vernonia amygdalina aqueous leaf extracts (VA extracts). VA extracts arrest cell proliferation and induce apoptosis in vitro and inhibit growth of implanted tumors and show chemo-preventive efficacy in vivo. Materials and Methods HRAS cells and MDA-MB-468 cells were subcutaneously implanted into nude mice with or without pretreatment with VA extracts before chemotherapeutic treatment with VA extracts and/or paclitaxel to evaluate their ability to inhibit tumor growth. Results The most significant reduction in tumor volume was observed in the MDA-MB-468 cell-induced tumors following VA extract pre-treatment compared to those from HRAS cell implantation. Conclusion VA extracts induce apoptosis, exhibit additive effects, inhibit tumor growth and display chemo-preventive actions against TNBCs. PMID:27466496

  3. Prolactin receptor attenuation induces zinc pool redistribution through ZnT2 and decreases invasion in MDA-MB-453 breast cancer cells

    SciTech Connect

    Bostanci, Zeynep; Alam, Samina; Soybel, David I.; Kelleher, Shannon L.

    2014-02-15

    Prolactin receptor (PRL-R) activation regulates cell differentiation, proliferation, cell survival and motility of breast cells. Prolactin (PRL) and PRL-R over-expression are strongly implicated in breast cancer, particularly contributing to tumor growth and invasion in the more aggressive estrogen-receptor negative (ER−) disease. PRL-R antagonists have been suggested as potential therapeutic agents; however, mechanisms through which PRL-R antagonists exert their actions are not well-understood. Zinc (Zn) is a regulatory factor for over 10% of the proteome, regulating critical cell processes such as proliferation, cell signaling, transcription, apoptosis and autophagy. PRL-R signaling regulates Zn metabolism in breast cells. Herein we determined effects of PRL-R attenuation on cellular Zn metabolism and cell function in a model of ER-, PRL-R over-expressing breast cancer cells (MDA-MB-453). PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. ZnT2-mediated lysosomal Zn sequestration was associated with reduced matrix metalloproteinase 2 (MMP-2) activity and decreased invasion. ZnT2-mediated Zn accumulation in mitochondria was associated with increased mitochondrial oxidation. Our results suggest that PRL-R antagonism in PRL-R over-expressing breast cancer cells may reduce invasion through the redistribution of intracellular Zn pools critical for cellular function. - Highlights: • PRL-R attenuation increased ZnT2 expression. • PRL-R attenuation increased lysosomal and mitochondrial Zn accumulation. • PRL-R attenuation decreased MMP-2 and invasion. • PRL-R antagonists may modulate lysosomal and mitochondrial Zn pools.

  4. The role of milk thistle extract in breast carcinoma cell line (MCF-7) apoptosis with doxorubicin.

    PubMed

    Rastegar, Hussein; Ahmadi Ashtiani, Hamidreza; Anjarani, Soghra; Bokaee, Saeed; Khaki, Arash; Javadi, Leila

    2013-01-01

    Breast cancer is the most commonly diagnosed invasive malignancy and first leading cause of cancer-related deaths in Iranian women. Based on silymarin's unique characteristics, its application in chemotherapy combined with doxorubicin can be effective to enhance the efficacy together with a reduced toxicity on normal tissues. The present study focus on evaluate the efficacy of silymarin in combination with doxorubicin, on viability and apoptosis of estrogen-dependent breast carcinoma cell line (MCF-7). After being cultured, MCF-7 cells were divided into 8 groups and treated as follows: 1st group received 75 μg silymarin, groups 2, 3, and 4 were treated with 10, 25, and 50 nM doxorubicin, respectively, and groups 5, 6, and 7 respectively received 10, 25, and 50 nM doxorubicin as well as 75 μg silymarin. Viability percentage and apoptosis of the cells were assessed with Trypan Blue staining after 16, 24, and 48 hours. Silymarin has a synergistic effect on the therapeutic potential of doxorubicin. Use of silymarin in combination with doxorubicin can be more effective on the therapeutic potential of doxorubicin and decreases its dose-limiting side effects.

  5. PIK3CA Mutations Are Associated With Decreased Benefit to Neoadjuvant Human Epidermal Growth Factor Receptor 2–Targeted Therapies in Breast Cancer

    PubMed Central

    Majewski, Ian J.; Nuciforo, Paolo; Mittempergher, Lorenza; Bosma, Astrid J.; Eidtmann, Holger; Holmes, Eileen; Sotiriou, Christos; Fumagalli, Debora; Jimenez, Jose; Aura, Claudia; Prudkin, Ludmila; Díaz-Delgado, Maria Carmen; de la Peña, Lorena; Loi, Sherene; Ellis, Catherine; Schultz, Nikolaus; de Azambuja, Evandro; Harbeck, Nadia; Piccart-Gebhart, Martine; Bernards, René; Baselga, José

    2015-01-01

    Purpose We investigated whether mutations in the gene encoding the phosphatidylinositol 3-kinase (PI3K) catalytic subunit (PIK3CA) correlates with response to neoadjuvant human epidermal growth factor receptor 2 (HER2) –targeted therapies in patients with breast cancer. Patients and Methods Baseline tissue biopsies were available from patients with HER2-positive early breast cancer who were enrolled onto the Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial (NeoALTTO). Activating mutations in PIK3CA were identified using mass spectrometry–based genotyping. Results PIK3CA mutations were identified in 23% of HER2-positive breast tumors, and these mutations were associated with poorer outcome in all of the treatment arms. Patients treated with a combination of trastuzumab and lapatinib who had wild-type PIK3CA obtained a total pathologic complete response (pCR) rate of 53.1%, which decreased to 28.6% in patients with tumors that carried PIK3CA activating mutations (P = .012). Conclusion Activating mutations in PIK3CA predicted poor pCR in patients with HER2-positive breast cancer treated with neoadjuvant therapies that target HER2. Consequently, the combination of anti-HER2 agents and PI3K inhibitors is being investigated. PMID:25559818

  6. Identification of multi-target effects of Huaier aqueous extract via microarray profiling in triple-negative breast cancer cells.

    PubMed

    Kong, Xiangnan; Ding, Xia; Yang, Qifeng

    2015-05-01

    Breast cancer is one of the most common malignant tumors in the world. Long-term maintenance treatment is important for breast cancer. However, effective maintenance treatment is lacking for triple-negative breast cancer (TNBC). Traditional Chinese medicine (TCM) has shown its potential anticancer roles as an effective maintenance treatment for TNBC. However its mechanisms remained unclear. In this study, we detected the differentially expressed genes (DEGs) after treatment with Huaier aqueous extract by using microarray profiling in MDA-MB-231 cells. Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene-gene interaction network were conducted to confirm the altered biological functions induced by Huaier extract. Screening of DEGs gave 387 genes (226 upregulated and 161 downregulated) in MDA-MB-231 cells which were regulated significantly by Huaier extract. GO and KEGG pathway analysis suggested that a number of functions were affected by Huaier, including proliferation, apoptosis, migration, and angiogenesis. Gene-gene interaction network showed the detailed molecular signal-net. Based on microarray data, we studied several functions of Huaier extract and in return verified the results of microarray profiling. This study had important guidance roles and indicated new research directions.

  7. Huaier Extract Induces Autophagic Cell Death by Inhibiting the mTOR/S6K Pathway in Breast Cancer Cells

    PubMed Central

    Li, Yaming; Zhang, Ning; Dong, Lun; Sun, Mingjuan; Cun, Jinjing; Zhang, Yan; Lv, Shangge; Yang, Qifeng

    2015-01-01

    Huaier extract is attracting increased attention due to its biological activities, including antitumor, anti-parasite and immunomodulatory effects. Here, we investigated the role of autophagy in Huaier-induced cytotoxicity in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cells. Huaier treatment inhibited cell viability in all three cell lines and induced various large membranous vacuoles in the cytoplasm. In addition, electron microscopy, MDC staining, accumulated expression of autophagy markers and flow cytometry revealed that Huaier extract triggered autophagy. Inhibition of autophagy attenuated Huaier-induced cell death. Furthermore, Huaier extract inhibited the mammalian target of the rapamycin (mTOR)/S6K pathway in breast cancer cells. After implanting MDA-MB-231 cells subcutaneously into the right flank of BALB/c nu/nu mice, Huaier extract induced autophagy and effectively inhibited xenograft tumor growth. This study is the first to show that Huaier-induced cytotoxicity is partially mediated through autophagic cell death in breast cancer cells through suppression of the mTOR/S6K pathway. PMID:26134510

  8. Treatment of advanced breast cancer with cyclophosphamide, 5-fluorouracil, and prednisone with and without methanol-extracted residue of BCG.

    PubMed

    Britell, J C; Ahmann, D L; Bisel, H F; Frytak, S; Ingle, J N; Rubin, J; O'Fallon, J R

    1979-01-01

    The value of immunotherapy as an adjuvant to chemotherapy for advanced breast cancer is an unsettled question. To clarify this issue, 71 women with measurable or evaluable metastatic breast cancer were randomized to receive cyclophosphamide, 5-fluorouracil, and prednisone (CFP) with or without methanol-extracted residue of Bacillus Calmette-Guerin (MER). The total regression rates were 52% (CFP) and 39% (CFP + MER), including complete regression rates of 13% (CFP) and 65% (CFP + MER). The median duration of regressions for CFP-treated patients was 257-261 days and for CFP + MER-treated patients was 385 days. The median time to progression was 248-261 days in the CFP group and 159 days in the CFP-MER group. Projected median survival for both treatment groups is 20 months. Immunotherapy (MER) as used in this study does not appear to augment regression rates or vurvival for patients with advanced breast cancer receiving CFP.

  9. Extract of Azadirachta indica (Neem) Leaf Induces Apoptosis in 4T1 Breast Cancer BALB/c Mice

    PubMed Central

    Othman, Fauziah; Motalleb, Gholamreza; Lam Tsuey Peng, Sally; Rahmat, Asmah; Fakurazi, Sharida; Pei Pei, Chong

    2011-01-01

    Objective: Azadirachta indica (Neem) has been used traditionally for many centuries. Some impressive therapeutic qualities have been discovered. However, the therapeutic effect of neem leaf extract in 4T1 breast cancer has not been documented. The purpose of the present study is to investigate the therapeutic effect of ethanolic Neem leaf extract in an in vivo 4T1 breast cancer model in mice. Materials and Methods: A total of 84 female BALB/c mice were divided randomly into 7 groups (3 non-cancerous groups and 4 cancerous groups) consisting of 12 mice per group. The 3 non-cancerous groups were normal mice treated with 0.5% of Tween 20 in phosphate buffer saline (PBS) (NC), 250 mg/kg Neem (N250) or 500 mg/kg Neem (N500). The 4 cancerous groups were; cancer controls treated with 0.5% of Tween 20 in PBS (CC), and cancerous mice treated with 0.5 µg/mL tamoxifen citrate (CT), 250 mg/kg Neem leaf extract (CN 250) or 500 mg/kg Neem leaf extract (CN 500). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to evaluate apoptosis (cell death) in the breast cancer tissues. SPSS software, version 14 was used for statistical analysis. Statistical significance was defined as p≤0.05. Non parametric analysis of variance (ANOVA) was performed with the Kruskal Wallis test for the TUNEL assays. Parametric data among the groups was compared using ANOVA. Results: TUNEL assays showed that the CN 250 and CN 500 groups had a higher incidence of apoptosis compared with the cancer controls. Conclusion: The findings showed that neem leaf extract induces apoptosis in 4T1 breast cancer BALB/c mice. PMID:23507990

  10. Extract of Azadirachta indica (Neem) Leaf Induces Apoptosis in 4T1 Breast Cancer BALB/c Mice.

    PubMed

    Othman, Fauziah; Motalleb, Gholamreza; Lam Tsuey Peng, Sally; Rahmat, Asmah; Fakurazi, Sharida; Pei Pei, Chong

    2011-01-01

    Azadirachta indica (Neem) has been used traditionally for many centuries. Some impressive therapeutic qualities have been discovered. However, the therapeutic effect of neem leaf extract in 4T1 breast cancer has not been documented. The purpose of the present study is to investigate the therapeutic effect of ethanolic Neem leaf extract in an in vivo 4T1 breast cancer model in mice. A total of 84 female BALB/c mice were divided randomly into 7 groups (3 non-cancerous groups and 4 cancerous groups) consisting of 12 mice per group. The 3 non-cancerous groups were normal mice treated with 0.5% of Tween 20 in phosphate buffer saline (PBS) (NC), 250 mg/kg Neem (N250) or 500 mg/kg Neem (N500). The 4 cancerous groups were; cancer controls treated with 0.5% of Tween 20 in PBS (CC), and cancerous mice treated with 0.5 µg/mL tamoxifen citrate (CT), 250 mg/kg Neem leaf extract (CN 250) or 500 mg/kg Neem leaf extract (CN 500). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were used to evaluate apoptosis (cell death) in the breast cancer tissues. SPSS software, version 14 was used for statistical analysis. Statistical significance was defined as p≤0.05. Non parametric analysis of variance (ANOVA) was performed with the Kruskal Wallis test for the TUNEL assays. Parametric data among the groups was compared using ANOVA. TUNEL assays showed that the CN 250 and CN 500 groups had a higher incidence of apoptosis compared with the cancer controls. The findings showed that neem leaf extract induces apoptosis in 4T1 breast cancer BALB/c mice.

  11. Red grape seed extract improves lipid profiles and decreases oxidized low-density lipoprotein in patients with mild hyperlipidemia.

    PubMed

    Razavi, Seyed-Mostafa; Gholamin, Sharareh; Eskandari, Ali; Mohsenian, Nakta; Ghorbanihaghjo, Amir; Delazar, Abbas; Rashtchizadeh, Nadereh; Keshtkar-Jahromi, Maryam; Argani, Hassan

    2013-03-01

    Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

  12. Antiproliferative effect of extracts from Aristolochia baetica and Origanum compactum on human breast cancer cell line MCF-7.

    PubMed

    Chaouki, Wahid; Leger, David Y; Eljastimi, Jamila; Beneytout, Jean-Louis; Hmamouchi, Mohamed

    2010-03-01

    Aristolochia baetica L. (Aristolochiaceae) and Origanum compactum Benth. (Lamiaceae) are native plants of Morocco used in traditional medicine. In order to systematically evaluate their potential activity on human breast cancer, four different polarity extracts from each plant were assessed in vitro for their antiproliferative effect on MCF-7 cells. As a result, several extracts of those plants showed potent cell proliferation inhibition on MCF-7 cells. Chloroform extract of A. baetica (IC50: 216.06 +/- 15 microg/mL) and ethyl acetate of O. compactum (IC50: 279.51 +/- 16 microg/mL) were the most active. Thin layer chromatography examination of the bioactive extracts of A. baetica and O. compactum showed the presence of aristolochic acid and betulinic acid, respectively. These results call for further studies of these extracts.

  13. Cytotoxic effect of the red beetroot (Beta vulgaris L.) extract compared to doxorubicin (Adriamycin) in the human prostate (PC-3) and breast (MCF-7) cancer cell lines.

    PubMed

    Kapadia, Govind J; Azuine, Magnus A; Rao, G Subba; Arai, Takanari; Iida, Akira; Tokuda, Harukuni

    2011-03-01

    Previous cancer chemoprevention studies from our laboratories and by other investigators have demonstrated that the extract of red beetroot (Beta vulgaris L.), the FDA approved red food color E162, can be effective in suppressing the development of multi-organ tumors in experimental animals. To further explore this finding, we have compared the cytotoxic effect of the red beetroot extract with anticancer drug, doxorubicin (adriamycin) in the androgen-independent human prostate cancer cells (PC-3) and in the well-established estrogen receptor-positive human breast cancer cells (MCF-7). This red colored anticancer antibiotic was selected for comparative cytotoxic study because its chemical structure with a planar configuration of an aromatic chromophore attached to a sugar molecule is remarkably similar to that of betanin, the beetroot extract constituent primarily responsible for its red color. Both doxorubicin and the beetroot extract exhibited a dose-dependent cytotoxic effect in the two cancer cell lines tested. Although the cytotoxicity of the beetroot extract was significantly lower when compared to doxorubicin, it continued to decrease the growth rate of the PC-3 cells (3.7% in 3 days vs. 12.5% in 7 days) when tested at the concentration of 29 µg/ml. In contrast, doxorubicin, at the same concentration level, completely inhibited the growth of the PC-3 cells in three days. Similarly, comparative studies in the normal human skin FC and liver HC cell lines showed that the beetroot extract had significantly lower cytotoxic effect than doxorubicin (8.6% vs. 100%, respectively, at 29 µg/ml concentration of each, three-day test period). The results suggest that betanin, the major betacyanin constituent, may play an important role in the cytotoxicity exhibited by the red beetroot extract. Further studies are needed to evaluate the chemopreventive potentials of the beetroot extract when used alone or in combination with doxorubicin to mitigate the toxic side

  14. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

    USDA-ARS?s Scientific Manuscript database

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

  15. Grape seed polyphenolic extract specifically decreases aβ*56 in the brains of Tg2576 mice.

    PubMed

    Liu, Peng; Kemper, Lisa J; Wang, Jun; Zahs, Kathleen R; Ashe, Karen H; Pasinetti, Giulio M

    2011-01-01

    Amyloid-β (Aβ) oligomers, found in the brains of Alzheimer's disease (AD) patients and transgenic mouse models of AD, cause synaptotoxicity and memory impairment. Grape seed polyphenolic extract (GSPE) inhibits Aβ oligomerization in vitro and attenuates cognitive impairment and AD-related neuropathology in the brains of transgenic mice. In the current study, GSPE was administered to Tg2576 mice for a period of five months. Treatment significantly decreased brain levels of Aβ*56, a 56-kDa Aβ oligomer previously shown to induce memory dysfunction in rodents, without changing the levels of transgenic amyloid-β protein precursor, monomeric Aβ, or other Aβ oligomers. These results thus provide the first demonstration that a safe and affordable intervention can lower the levels of a memory-impairing Aβ oligomer in vivo and strongly suggest that GSPE should be further tested as a potential prevention and/or therapy for AD.

  16. Spatholobus suberectus Column Extract Inhibits Estrogen Receptor Positive Breast Cancer via Suppressing ER MAPK PI3K/AKT Pathway

    PubMed Central

    Sun, Jia-Qi; Zhang, Gan-Lin; Zhang, Yi; Nan, Nan; Sun, Xu; Yu, Ming-Wei; Wang, Hong

    2016-01-01

    Although Chinese herbal compounds have long been alternatively applied for cancer treatment in China, their treatment effects have not been sufficiently investigated. The Chinese herb Spatholobus suberectus is commonly prescribed to cancer patients. HPLC analysis has shown that the main components of Spatholobus suberectus are flavonoids that can be classified as phytoestrogens, having a structure similar to estrogen. This study was designed to investigate the effects of Spatholobus suberectus column extract (SSCE) on the estrogen receptor-positive (ER+) breast cancer cell line MCF-7 and its possible molecular mechanism. In our study, MTT assay was performed to evaluate cell viability. The results show that SSCE (80, 160, and 320 μg/ml) significantly decreased the viability of MCF-7 cells. SSCE also triggered apoptosis, arrested the cell cycle at the G0/G1 phase, and inhibited cell migration. A dual-luciferase reporter system showed that SSCE suppressed intranuclear p-ER activity; Western blot analysis confirmed the repressed expression of phosphorylated-ER alpha (p-ERα), ERK1/2, p-ERK1/2, AKT, p-AKT, p-mTOR, PI3K, and p-PI3K, indicating that SSCE suppressed the MAPK PI3K/AKT signaling pathway. Collectively, our results suggest that SSCE causes apoptosis, an arrest in the G0/G1 phase, and a decrease in migration in ER+ MCF-7 cells via hypoactivity of the ER and suppression of the MAPK PI3K/AKT pathway. PMID:28096885

  17. Induction of Mitochondria Mediated Apoptosis in Human Breast Cancer Cells (T-47D) by Annona reticulata L. Leaves Methanolic Extracts.

    PubMed

    Roham, Pratiksha H; Kharat, Kiran R; Mungde, Priyanka; Jadhav, Mahadev A; Makhija, Surinder J

    2016-01-01

    Annona reticulata Linn. (Common name: Bullock's-heart) (Annonaceae family) is a semi-evergreen and small deciduous tree. The extracts of various parts of Annona reticulata L. have been reported as cytotoxic to many cancer cells. Annona reticulata L. leaves' methanolic extract (ARME) was prepared and used against the breast cancer cells. The breast cancer cells (T-47D) viability and IC50 were evaluated by Vybrant® MTT Cell Proliferation Assay Kit. Detection of phosphatidylserine on membranes of apoptotic cells was done by Attune flow cytometer. RNA transcripts were quantified in ARME treated and untreated cells. Finally, the Vybrant® FAM Poly Caspases assay kit was used for analysis of polycaspases activity in T-47D cells. The IC50 (5 ± 0.5 µg/mL) of the ARME was found against breast cancer cells (T-47D). The Paclitaxel was used as a control standard drug for the study. The downregulation of Bcl-2 and upregulation of Bax and Bak, and caspases activation suggested induction of apoptosis in T-47D cells by ARME through mitochondrial pathway. The cell cycle halted at G2/M phase in the ARME treated cells. The ARME was found to be effective against Breast cancer cells (T-47D).

  18. The inhibitory effect of roasted licorice extract on human metastatic breast cancer cell-induced bone destruction.

    PubMed

    Lee, Sun Kyoung; Park, Kwang-Kyun; Park, Jung Han Yoon; Lim, Soon Sung; Chung, Won-Yoon

    2013-12-01

    The aim of this study was to determine whether the ethanol extract of roasted licorice (rLE) could inhibit breast cancer-mediated bone destruction. rLE treatment reduced the viability of MDA-MB-231 human metastatic breast cancer cells but did not show any cytotoxicity in hFOB1.19 human osteoblastic cells and murine bone marrow-derived macrophages (BMMs). rLE inhibited expression and secretion of receptor activator of nuclear factor κB ligand (RANKL) as well as the mRNA and protein expression of cyclooxygenase-2 in osteoblastic cells exposed to the conditioned medium of breast cancer cells. rLE dramatically inhibited RANKL-induced osteoclastogenesis in BMMs, thereby reducing osteoclast-mediated pit formation. Moreover, treatment with licochalcone A and isoliquiritigenin as the active components, whose contents are increased by the roasting process, remarkably suppressed RANKL-induced osteoclast formation in BMMs, respectively. Furthermore, orally administered rLE substantially blocked tumor growth and bone destruction in mice inoculated with breast cancer cells in the tibiae. Serum levels of tartrate-resistant acid phosphatase and C-terminal cross-linking telopeptide of type I collagen and trabecular bone morphometric parameters were reversed to almost the same levels as the control mice by the rLE treatment. In conclusion, rLE may be a beneficial agent for preventing and treating bone destruction in patients with breast cancer.

  19. Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival.

    PubMed

    Metodieva, Gergana; Adoki, Samson; Lausen, Berthold; Metodiev, Metodi V

    2016-06-01

    SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of deregulations exists: an unexpected SCRIB exon usage pattern appears to mark a more malignant tumor phenotype and significantly correlates with survival. Conserved exons encoding the leucine-rich repeats tend to be overexpressed while others are underused. Mechanistic studies revealed that the underused exons encode part of the protein necessary for interaction with Vimentin and Numa1, a protein which is required for proper positioning of the mitotic spindle. Thus, the inclusion/exclusion of specific SCRIB exons is a mechanistic hallmark of breast cancer, which could potentially be exploited to develop more efficient diagnostics and therapies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Obesity as an independent risk factor for decreased survival in node-positive high-risk breast cancer.

    PubMed

    Scholz, Christoph; Andergassen, U; Hepp, P; Schindlbeck, C; Friedl, Thomas W P; Harbeck, N; Kiechle, M; Sommer, H; Hauner, H; Friese, K; Rack, B; Janni, W

    2015-06-01

    Obese breast cancer patients have a higher risk of lymph node metastasis and a poorer prognosis compared to patients with normal weight. For obese women with node-positive breast cancer, an association between body weight and prognosis remains unclear. In this retrospective study, we analyzed patient data from the Phase-III ADEBAR trial, in which high-risk breast cancer patients (pT1-4, pN2-3, pM0) were randomized into a docetaxel-based versus epirubicin-based chemotherapy regimen. Patients were grouped according to their BMI value as underweight/normal weight (BMI < 25 kg/m(2); n = 543), overweight (BMI 25-29.9 kg/m(2); n = 482) or obese (BMI ≥ 30 kg/m(2); n = 285). Overweight and obese patients were older, had larger tumors and were more likely to be postmenopausal at the time of diagnosis compared to underweight/normal-weight patients (all p < 0.001). Multivariate Cox regression analyses adjusting for age and histopathological tumor features showed that obese patients had a significantly shorter disease-free survival (DFS; HR 1.43; 95 % CI 1.11-1.86; p = 0.006) and overall survival (OS; HR 1.56; 95 % CI 1.14-2.14; p = 0.006) than non-obese patients. Subgroup analyses revealed that the differences in DFS and OS were significant for postmenopausal but not for premenopausal patients, and that the survival benefit of non-obese patients was more pronounced in women with hormone-receptor-positive disease. Obesity constitutes an independent, adverse prognostic factor in high-risk node-positive breast cancer patients, in particular for postmenopausal women and women with hormone-receptor-positive disease.

  1. The Hydroalcoholic Extract of Matricaria chamomilla Suppresses Migration and Invasion of Human Breast Cancer MDA-MB-468 and MCF-7 Cell Lines

    PubMed Central

    Nikseresht, Mohsen; Kamali, Ali Mohammad; Rahimi, Hamid Reza; Delaviz, Hamdollah; Toori, Mehdi Akbartabar; Kashani, Iraj Ragerdi; Mahmoudi, Reza

    2017-01-01

    Background: Matricaria chamomilla is an aromatic plant with antioxidant, anticancer, and anti-inflammatory properties. However, the inhibitory role of M. chamomilla on migration and invasion of human breast cancer cells remains unclear. Objective: This study investigated the methods to evaluate these anticancer mechanisms of M. chamomilla on human breast cancer MCF-7 and MDA-MB-468 cell lines. Materials and Methods: The cells were treated with hydroalcoholic extract of M. chamomilla at different concentrations (50–1300 μg/mL) for 24, 48, and 72 h in a culture medium containing 10% fetal bovine serum. This study quantified the 50% growth inhibition concentrations (IC50) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; apoptosis and necrosis through Hoechst 33342/propidium iodide staining; cell proliferation and clone formation by clonogenic assay as well as cellular migration, invasion, and attachment. After 24, 48, and 72 h of treatment, the IC50levels were 992 ± 2.3 μg/mL, 893 ± 5.4 μg/mL, and 785 ± 4.8 μg/mL against MDA-MB-468, respectively, and 1288 ± 5.6 μg/mL, 926 ± 2.5 μg/mL, and 921 ± 3.5 μg/mL, against MCF-7, respectively. Furthermore, increasing the extract concentrations induced cellular apoptosis and necrosis and decreased cellular invasion or migration through 8 μm pores, colonization and attachment in a dose-dependent manner. Results: It indicated time- and dose-dependent anti-invasive and antimigrative or proliferative and antitoxic effects of hydroalcoholic extract of aerial parts of chamomile on breast cancer cells. Conclusion: This study demonstrated an effective plant in preventing or treating breast cancer. SUMMARY Antioxidant compounds in Matricaria chamomilla have anticancer effects.Hydroalcoholic extract of M. chamomilla controls cellular proliferation and apoptosis induction.Hoechst 33342/propidium iodide staining suggested that the extract induces apoptosis more than necrosis.Hydroalcoholic extract of M

  2. The Hydroalcoholic Extract of Matricaria chamomilla Suppresses Migration and Invasion of Human Breast Cancer MDA-MB-468 and MCF-7 Cell Lines.

    PubMed

    Nikseresht, Mohsen; Kamali, Ali Mohammad; Rahimi, Hamid Reza; Delaviz, Hamdollah; Toori, Mehdi Akbartabar; Kashani, Iraj Ragerdi; Mahmoudi, Reza

    2017-01-01

    Matricaria chamomilla is an aromatic plant with antioxidant, anticancer, and anti-inflammatory properties. However, the inhibitory role of M. chamomilla on migration and invasion of human breast cancer cells remains unclear. This study investigated the methods to evaluate these anticancer mechanisms of M. chamomilla on human breast cancer MCF-7 and MDA-MB-468 cell lines. The cells were treated with hydroalcoholic extract of M. chamomilla at different concentrations (50-1300 μg/mL) for 24, 48, and 72 h in a culture medium containing 10% fetal bovine serum. This study quantified the 50% growth inhibition concentrations (IC50) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; apoptosis and necrosis through Hoechst 33342/propidium iodide staining; cell proliferation and clone formation by clonogenic assay as well as cellular migration, invasion, and attachment. After 24, 48, and 72 h of treatment, the IC50levels were 992 ± 2.3 μg/mL, 893 ± 5.4 μg/mL, and 785 ± 4.8 μg/mL against MDA-MB-468, respectively, and 1288 ± 5.6 μg/mL, 926 ± 2.5 μg/mL, and 921 ± 3.5 μg/mL, against MCF-7, respectively. Furthermore, increasing the extract concentrations induced cellular apoptosis and necrosis and decreased cellular invasion or migration through 8 μm pores, colonization and attachment in a dose-dependent manner. It indicated time- and dose-dependent anti-invasive and antimigrative or proliferative and antitoxic effects of hydroalcoholic extract of aerial parts of chamomile on breast cancer cells. This study demonstrated an effective plant in preventing or treating breast cancer. Antioxidant compounds in Matricaria chamomilla have anticancer effects.Hydroalcoholic extract of M. chamomilla controls cellular proliferation and apoptosis induction.Hoechst 33342/propidium iodide staining suggested that the extract induces apoptosis more than necrosis.Hydroalcoholic extract of M. chamomilla prevents colonization and cellular migration of human breast

  3. Chrysin, Abundant in Morinda citrifolia Fruit Water-EtOAc Extracts, Combined with Apigenin Synergistically Induced Apoptosis and Inhibited Migration in Human Breast and Liver Cancer Cells.

    PubMed

    Huang, Cheng; Wei, Yu-Xuan; Shen, Ma-Ching; Tu, Yu-Hsuan; Wang, Chia-Chi; Huang, Hsiu-Chen

    2016-06-01

    The composition of Morinda citrifolia (M. citrifolia) was determined using high-performance liquid chromatography (HPLC), and the anticancer effects of M. citrifolia extract evaluated in HepG2, Huh7, and MDA-MB-231 cancer cells. M. citrifolia fruit extracts were obtained by using five different organic solvents, including hexane (Hex), methanol (MeOH), ethyl acetate (EtOAc), chloroform (CHCl3), and ethanol (EtOH). The water-EtOAc extracts from M. citrifolia fruits was found to have the highest anticancer activity. HPLC data revealed the predominance of chrysin in water-EtOAc extracts of M. citrifolia fruit. Furthermore, the combined effects of cotreatment with apigenin and chrysin on liver and breast cancer were investigated. Treatment with apigenin plus chrysin for 72-96 h reduced HepG2 and MDA-MB-231 cell viability and induced apoptosis through down-regulation of S-phase kinase-associated protein-2 (Skp2) and low-density lipoprotein receptor-related protein 6 (LRP6) expression. However, the combination treatment for 36 h synergistically decreased MDA-MB-231 cell motility but not cell viability through down-regulation of MMP2, MMP9, fibronectin, and snail in MDA-MB-231 cells. Additionally, chrysin combined with apigenin also suppressed tumor growth in human MDA-MB-231 breast cancer cells xenograft through down-regulation of ki-67 and Skp2 protein. The experimental results showed that chrysin combined with apigenin can reduce HepG2 and MDA-MB-231 proliferation and cell motility and induce apoptosis. It also offers opportunities for exploring new drug targets, and further investigations are underway in this regard.

  4. Effect of Boswellia Thurifera Gum Methanol Extract on Cytotoxicity and P53 Gene Expression in Human Breast Cancer Cell Line

    PubMed Central

    Yazdanpanahi, Nasrin; Behbahani, Mandana; Yektaeian, Afsaneh

    2014-01-01

    Boswellia has been widely used in traditional medicine for the treatment of different diseases such as cancer in Iran. The aim of this study was to evaluate the effect of the gum methanol extract of Boswellia thurifera on the viability and P53 gene expression of cultured breast cancer cells. The gum methanol extract was obtained in various concentrations using the maceration method. Normal (HEK-293) and cancer (MDA-MB-231) human cells were cultured and treated with various concentrations of the extract. Then MTT assay was used for the study of cytotoxic effect of the extract and real time PCR method was also applied for the investigation of P53 gene expression in cancer cells. The IC50 of the extract against cancer cells was 80 µg/mL and had less cytotoxic effect in normal cells. The effect of the extract was dose dependent. Induction of P53 expression by extract was also significantly more in treated cancer cells than untreated cells. This inductive effect in cells was higher after 12 h treatment than it was after 6 h. The results of the current study show that gum methanol extract of Boswellia thurifera has probably anti-cancer effects and could induce P53 gene transcription and toxicity in the cultured breast cancer cell line. The increase of P53 gene specific mRNA may be a mechanism of gum methanol extract induced cytotoxicity. However, for a definitive conclusion, further studies on other cell lines as well as animal models and subsequent clinical studies are warranted. PMID:25237368

  5. Antioxidant and apoptotic effects of an aqueous extract of Urtica dioica on the MCF-7 human breast cancer cell line.

    PubMed

    Fattahi, Sadegh; Ardekani, Ali Motevalizadeh; Zabihi, Ebrahim; Abedian, Zeinab; Mostafazadeh, Amrollah; Pourbagher, Roghayeh; Akhavan-Niaki, Haleh

    2013-01-01

    Breast cancer is the most prevalent cancer and one of the leading causes of death among women in the world. Plants and herbs may play an important role in complementary or alternative treatment. The aim of this study was to evaluate the antioxidant and anti-proliferative potential of Urtica dioica. The anti oxidant activity of an aqueous extract of Urtica dioica leaf was measured by MTT assay and the FRAP method while its anti-proliferative activity on the human breast cancer cell line (MCF-7) and fibroblasts isolated from foreskin tissue was evaluated using MTT assay. Mechanisms leading to apoptosis were also investigated at the molecular level by measuring the amount of anti and pro-apoptotic proteins and at the cellular level by studying DNA fragmentation and annexin V staining by flow cytometry. The aqueous extract of Urtica dioica showed antioxidant effects with a correlation coefficient of r(2)=0.997. Dose-dependent and anti-proliferative effects of the extract were observed only on MCF-7 cells after 72 hrs with an IC50 value of 2 mg/ml. This anti proliferative activity was associated with an increase of apoptosis as demonstrated by DNA fragmentation, the appearance of apoptotic cells in flow cytometry analysis and an increase of the amount of calpain 1, calpastatin, caspase 3, caspase 9, Bax and Bcl-2, all proteins involved in the apoptotic pathway. This is the first time such in vitro antiproliferative effect of aqueous extract of Urtica dioica leaf has been described for a breast cancer cell line. Our findings warrant further research on Urtica dioica as a potential chemotherapeutic agent for breast cancer.

  6. Effect of Polygonatum odoratum extract on human breast cancer MDA-MB-231 cell proliferation and apoptosis

    PubMed Central

    Tai, Yu; Sun, Yi-Ming; Zou, Xue; Pan, Qiong; Lan, Ya-Dong; Huo, Qiang; Zhu, Jing-Wen; Guo, Fei; Zheng, Chang-Quan; Wu, Cheng-Zhu; Liu, Hao

    2016-01-01

    Traditional Chinese medicine (TCM) is important in the provision of anti-tumor drugs. Recently, studies have shown that certain types of TCM agents are able to control the growth of tumors, enhance the body's immune function and enhance the therapeutic effect of chemotherapeutic drugs. In women, breast carcinoma is the most common tumor type and the second most common cause of death from cancer. Polygonatum odoratum (P. odoratum) is commonly used in TCM. The aim of the present study was to investigate the effects of P. odoratum extract on the proliferation and apoptosis of MDA-MB-231 breast cancer cells. Cell proliferation was assessed using MTT and colony formation assays. In addition, propidium iodide (PI)/Annexin V-FITC staining was used to investigate the apoptosis of MDA-MB-231 cells following treatment with P. odoratum extract. The protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were also detected using western blot analysis, while a JC-1 staining assay was used to assess the mitochondrial membrane potential (ΔΨm). The results of the MTT assay showed that the proliferation and colony formation of MDA-MB-231 cells were inhibited following treatment with the extract. Furthermore, the PI/Annexin-V staining showed that the apoptosis of MDA-MB-231 cells was enhanced by the extract, in a concentration-dependent manner. The extract also lowered the ΔΨm of MDA-MB-231 cells, upregulated the expression of Bax and inhibited the expression of Bcl-2. In conclusion, these results showed that the P. odoratum extract inhibited the proliferation and induced apoptosis of breast cancer MDA-MB-231 cells. PMID:27698772

  7. Effect of Polygonatum odoratum extract on human breast cancer MDA-MB-231 cell proliferation and apoptosis.

    PubMed

    Tai, Yu; Sun, Yi-Ming; Zou, Xue; Pan, Qiong; Lan, Ya-Dong; Huo, Qiang; Zhu, Jing-Wen; Guo, Fei; Zheng, Chang-Quan; Wu, Cheng-Zhu; Liu, Hao

    2016-10-01

    Traditional Chinese medicine (TCM) is important in the provision of anti-tumor drugs. Recently, studies have shown that certain types of TCM agents are able to control the growth of tumors, enhance the body's immune function and enhance the therapeutic effect of chemotherapeutic drugs. In women, breast carcinoma is the most common tumor type and the second most common cause of death from cancer. Polygonatum odoratum (P. odoratum) is commonly used in TCM. The aim of the present study was to investigate the effects of P. odoratum extract on the proliferation and apoptosis of MDA-MB-231 breast cancer cells. Cell proliferation was assessed using MTT and colony formation assays. In addition, propidium iodide (PI)/Annexin V-FITC staining was used to investigate the apoptosis of MDA-MB-231 cells following treatment with P. odoratum extract. The protein expression levels of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) were also detected using western blot analysis, while a JC-1 staining assay was used to assess the mitochondrial membrane potential (ΔΨm). The results of the MTT assay showed that the proliferation and colony formation of MDA-MB-231 cells were inhibited following treatment with the extract. Furthermore, the PI/Annexin-V staining showed that the apoptosis of MDA-MB-231 cells was enhanced by the extract, in a concentration-dependent manner. The extract also lowered the ΔΨm of MDA-MB-231 cells, upregulated the expression of Bax and inhibited the expression of Bcl-2. In conclusion, these results showed that the P. odoratum extract inhibited the proliferation and induced apoptosis of breast cancer MDA-MB-231 cells.

  8. Chemotherapy modulates the biological activity of breast cancer patients plasma: the protective properties of black chokeberry extract.

    PubMed

    Kędzierska, Magdalena; Malinowska, Joanna; Kontek, Bogdan; Kołodziejczyk-Czepas, Joanna; Czernek, Urszula; Potemski, Piotr; Piekarski, Janusz; Jeziorski, Arkadiusz; Olas, Beata

    2013-03-01

    In breast cancer patients (before and during anti-cancer therapy) oxidative/nitrative damage to various molecules is observed. Furthermore, anti-cancer treatments may also influence the hemostatic properties of blood platelets and plasma. The aim of our study was to assess the effect of oxidative/nitrative stress (estimated by measurements of the levels of carbonyl groups and 3-nitrotyrosine in proteins--ELISA and C-ELISA methods, respectively; lipid peroxidation and total antioxidant level--TAS) on the selected parameters of hemostatic activity of plasma (the process of fibrin polymerization and lysis) collected from breast cancer patients after surgery and after various phases of chemotherapy (doxorubicin and cyclophosphamide). Subsequently, we also evaluated the level of oxidative/nitrative stress and hemostatic activity in plasma from these patients in the presence of the commercial extract of Aronia melanocarpa (Aronox®) in vitro. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy in Medical University of Lodz, Poland. We observed increased levels of biomarkers of oxidative/nitrative stress in plasma from patients with breast cancer (before or after surgery and after various phases of chemotherapy) in comparison to healthy group. Our further experiments demonstrated the hemostatic activity of plasma from the investigated patients differs from hemostatic properties of plasma obtained from healthy volunteers. We also recognize the existence of a relationship between oxidative stress (measured by the level of carbonyl groups) and changes of hemostasis in breast cancer patients after I and IV phases of chemotherapy. Moreover, the obtained results showed that the commercial extract from A. melanocarpa berries significantly reduced, in in vitro system, the oxidative/nitrative stress and hemostasis changes in plasma from breast cancer patients, after surgery and different phases of chemotherapy. Considering the data

  9. The selective cytotoxicity elicited by phytochemical extract from Senecio graveolens (Asteraceae) on breast cancer cells is enhanced by hypoxia.

    PubMed

    Echiburú-Chau, Carlos; Alfaro-Lira, Susana; Brown, Nelson; Salas, Cristian O; Cuellar, Mauricio; Santander, Javier; Ogalde, Juan Pablo; Rothhammer, Francisco

    2014-04-01

    Breast cancer is the second cause of cancer‑related deaths in woman and the incidence of the disease has increased worldwide, in part due to improvements in early detection. Several drugs with anticancer effects have been extracted from plants in the last 20 years, many of which are particularly effective against breast cancer cells. In particular, we have become interested in the ethanolic extract from Senecio graveolens (synonym of S. nutans), a plant commonly called Chachacoma, in an effort to isolate compounds that could demonstrate cytotoxic effects on breast cancer cells. Senecio (Asteraceae) is the largest gender in Chile comprising approximatly 200 species. These herbs inhabit areas over 3,500 meters above the sea level in the Andes Mountains. S. graveolens is commonly used by local communities for its medicinal properties, particularly its capacity to ameliorate high-altitude-associated sickness. The cytotoxic effect of the alcoholic extract from S. graveolens, as well as its most abundant compound 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone, were tested in the breast cancer cell lines ZR-75-1, MCF-7 and MDA-MB‑231, and non-tumorigenic MCF-10F cells. We show that the phytochemical extract was able to induce cytotoxicity in cancer cells but not in MCF-10F. Importantly, this effect was enhanced under hypoxic conditions. However, 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone, the main compound, did not by itself show an effective anticarcinogenic activity in comparison to the whole extract. Interestingly, the cytotoxic effect of the phytochemical extract was dependent on the basal MnSOD protein expression. Thus, cytotoxicity was increased when MnSOD levels were low, but resistance was evident when protein levels were high. Additionally, the crude extract seems to trigger cell death by a variety of processes, including autophagy, apoptosis and necrosis, in MCF-7 cells. In summary, S. graveolens extract possess anticancer activity displaying a specific

  10. [Inhibition of human breast cancer cell line BCap-37 by flavonoid extract of wheat germ in vitro].

    PubMed

    Xu, G; Zhao, X; Zhao, L; Xu, H

    1999-05-30

    Cell growth and proliferation were measured by microculture tetrazolium(MTT) assay, cell colony-forming assay and the synthesis of DNA by 3H-thymidine incorporation. Flavonoid extract of wheat germ resulted to a dose-dependent, time-dependent growth inhibition, reduction of colony and 3H-thymiding incorporation in DNA of human breast cancer cell BCap-37. These findings indicated that the flavonoid extract of wheat germ can inhibit tumor cell growth and proliferation by blocking DNA synthesis in vitro.

  11. Improvement of DNA repair in lymphocytes of breast cancer patients treated with Viscum album extract (Iscador).

    PubMed

    Kovacs, E; Hajto, T; Hostanska, K

    1991-01-01

    We investigated alteration in DNA repair during therapy with an immunomodulator. 14 patients with advanced breast cancer were treated parenterally with Iscador, an extract of Viscum album (mistletoe). As a parameter for measurement of DNA repair the incorporation of (3H) thymidine into DNA of unstimulated lymphocytes after ultra violet light (UV) damage was taken. The DNA repair values in the patients were very low before treatment and on day 1: on average 16% of those in a healthy control population. Values started to increase on day 2 and on days 7-9 were on average 2.7 times higher than before treatment. 12/14 patients showed an improvement in repair. The values of spontaneous DNA synthesis were not altered during the treatment. We suggest that the increase of DNA repair could be due to a stimulation of repair enzymes by lymphokines or cytokines secreted by activated leukocytes or an alteration in the susceptibility to exogenic agents resulting in less damage.

  12. Decreased expression of Yes-associated protein is associated with outcome in the luminal A breast cancer subgroup and with an impaired tamoxifen response.

    PubMed

    Lehn, Sophie; Tobin, Nicholas P; Sims, Andrew H; Stål, Olle; Jirström, Karin; Axelson, Håkan; Landberg, Göran

    2014-02-22

    Yes-associated protein (YAP1) is frequently reported to function as an oncogene in many types of cancer, but in breast cancer results remain controversial. We set out to clarify the role of YAP1 in breast cancer by examining gene and protein expression in subgroups of patient material and by downregulating YAP1 in vitro and studying its role in response to the widely used anti-estrogen tamoxifen. YAP1 protein intensity was scored as absent, weak, intermediate or strong in two primary breast cancer cohorts (n = 144 and n = 564) and mRNA expression of YAP1 was evaluated in a gene expression dataset (n = 1107). Recurrence-free survival was analysed using the log-rank test and Cox multivariate analysis was used to test for independence. WST-1 assay was employed to measure cell viability and a luciferase ERE (estrogen responsive element) construct was used to study the effect of tamoxifen, following downregulation of YAP1 using siRNAs. In the ER+ (Estrogen Receptor α positive) subgroup of the randomised cohort, YAP1 expression was inversely correlated to histological grade and proliferation (p = 0.001 and p = 0.016, respectively) whereas in the ER- (Estrogen Receptor α negative) subgroup YAP1 expression correlated positively to proliferation (p = 0.005). Notably, low YAP1 mRNA was independently associated with decreased recurrence-free survival in the gene expression dataset, specifically for the luminal A subgroup (p < 0.001) which includes low proliferating tumours of lower grade, usually associated with a good prognosis. This subgroup specificity led us to hypothesize that YAP1 may be important for response to endocrine therapies, such as tamoxifen, extensively used for luminal A breast cancers. In a tamoxifen randomised patient material, absent YAP1 protein expression was associated with impaired tamoxifen response which was significant upon interaction analysis (p = 0.042). YAP1 downregulation resulted in increased progesterone receptor (PgR) expression and a

  13. Validation of an optimized method for the determination of iodine in human breast milk by inductively coupled plasma mass spectrometry (ICPMS) after tetramethylammonium hydroxide extraction.

    PubMed

    Huynh, Dao; Zhou, Shao Jia; Gibson, Robert; Palmer, Lyndon; Muhlhausler, Beverly

    2015-01-01

    In this study a novel method to determine iodine concentrations in human breast milk was developed and validated. The iodine was analyzed by inductively coupled plasma mass spectrometry (ICPMS) following tetramethylammonium hydroxide (TMAH) extraction at 90°C in disposable polypropylene tubes. While similar approaches have been used previously, this method adopted a shorter extraction time (1h vs. 3h) and used antimony (Sb) as the internal standard, which exhibited greater stability in breast milk and milk powder matrices compared to tellurium (Te). Method validation included: defining iodine linearity up to 200μgL(-1); confirming recovery of iodine from NIST 1549 milk powder. A recovery of 94-98% was also achieved for the NIST 1549 milk powder and human breast milk samples spiked with sodium iodide and thyroxine (T4) solutions. The method quantitation limit (MQL) for human breast milk was 1.6μgL(-1). The intra-assay and inter-assay coefficient of variation for the breast milk samples and NIST powder were <1% and <3.5%, respectively. NIST 1549 milk powder, human breast milk samples and calibration standards spiked with the internal standard were all stable for at least 2.5 months after extraction. The results of the validation process confirmed that this newly developed method provides greater accuracy and precision in the assessment of iodine concentrations in human breast milk than previous methods and therefore offers a more reliable approach for assessing iodine concentrations in human breast milk.

  14. Proapoptotic and Antimetastatic Properties of Supercritical CO2 Extract of Nigella sativa Linn. Against Breast Cancer Cells

    PubMed Central

    Baharetha, Hussein M.; Nassar, Zeyad D.; Aisha, Abdalrahim F.; Ahamed, Mohamed B. Khadeer; Al-Suede, Foaud Saleih R.; Kadir, Mohd Omar Abd; Ismail, Zhari

    2013-01-01

    Abstract Nigella sativa, commonly referred as black cumin, is a popular spice that has been used since the ancient Egyptians. It has traditionally been used for treatment of various human ailments ranging from fever to intestinal disturbances to cancer. This study investigated the apoptotic, antimetastatic, and anticancer activities of supercritical carbon dioxide (SC-CO2) extracts of the seeds of N. sativa Linn. against estrogen-dependent human breast cancer cells (MCF-7). Twelve extracts were prepared from N. sativa seeds using the SC-CO2 extraction method by varying pressure and temperature. Extracts were analyzed using FTIR and UV-Vis spectrometry. Cytotoxicity of the extracts was evaluated on various human cancer and normal cell lines. Of the 12 extracts, 1 extract (A3) that was prepared at 60°C and 2500 psi (∼17.24 MPa) showed selective antiproliferative activity against MCF-7 cells with an IC50 of 53.34±2.15 μg/mL. Induction of apoptosis was confirmed by evaluating caspases activities and observing the cells under a scanning electron microscope. In vitro antimetastatic properties of A3 were investigated by colony formation, cell migration, and cell invasion assays. The elevated levels of caspases in A3 treated MCF-7 cells suggest that A3 is proapoptotic. Further nuclear condensation and fragmentation studies confirmed that A3 induces cytotoxicity through the apoptosis pathway. A3 also demonstrated remarkable inhibition in migration and invasion assays of MCF-7 cells at subcytotoxic concentrations. Thus, this study highlights the therapeutic potentials of SC-CO2 extract of N. sativa in targeting breast cancer. PMID:24328702

  15. Proapoptotic and antimetastatic properties of supercritical CO2 extract of Nigella sativa Linn. against breast cancer cells.

    PubMed

    Baharetha, Hussein M; Nassar, Zeyad D; Aisha, Abdalrahim F; Ahamed, Mohamed B Khadeer; Al-Suede, Foaud Saleih R; Abd Kadir, Mohd Omar; Ismail, Zhari; Majid, Amin Malik Shah Abdul

    2013-12-01

    Nigella sativa, commonly referred as black cumin, is a popular spice that has been used since the ancient Egyptians. It has traditionally been used for treatment of various human ailments ranging from fever to intestinal disturbances to cancer. This study investigated the apoptotic, antimetastatic, and anticancer activities of supercritical carbon dioxide (SC-CO2) extracts of the seeds of N. sativa Linn. against estrogen-dependent human breast cancer cells (MCF-7). Twelve extracts were prepared from N. sativa seeds using the SC-CO2 extraction method by varying pressure and temperature. Extracts were analyzed using FTIR and UV-Vis spectrometry. Cytotoxicity of the extracts was evaluated on various human cancer and normal cell lines. Of the 12 extracts, 1 extract (A3) that was prepared at 60°C and 2500 psi (~17.24 MPa) showed selective antiproliferative activity against MCF-7 cells with an IC50 of 53.34±2.15 μg/mL. Induction of apoptosis was confirmed by evaluating caspases activities and observing the cells under a scanning electron microscope. In vitro antimetastatic properties of A3 were investigated by colony formation, cell migration, and cell invasion assays. The elevated levels of caspases in A3 treated MCF-7 cells suggest that A3 is proapoptotic. Further nuclear condensation and fragmentation studies confirmed that A3 induces cytotoxicity through the apoptosis pathway. A3 also demonstrated remarkable inhibition in migration and invasion assays of MCF-7 cells at subcytotoxic concentrations. Thus, this study highlights the therapeutic potentials of SC-CO2 extract of N. sativa in targeting breast cancer.

  16. Application of computer-extracted breast tissue texture features in predicting false-positive recalls from screening mammography

    NASA Astrophysics Data System (ADS)

    Ray, Shonket; Choi, Jae Y.; Keller, Brad M.; Chen, Jinbo; Conant, Emily F.; Kontos, Despina

    2014-03-01

    Mammographic texture features have been shown to have value in breast cancer risk assessment. Previous models have also been developed that use computer-extracted mammographic features of breast tissue complexity to predict the risk of false-positive (FP) recall from breast cancer screening with digital mammography. This work details a novel locallyadaptive parenchymal texture analysis algorithm that identifies and extracts mammographic features of local parenchymal tissue complexity potentially relevant for false-positive biopsy prediction. This algorithm has two important aspects: (1) the adaptive nature of automatically determining an optimal number of region-of-interests (ROIs) in the image and each ROI's corresponding size based on the parenchymal tissue distribution over the whole breast region and (2) characterizing both the local and global mammographic appearances of the parenchymal tissue that could provide more discriminative information for FP biopsy risk prediction. Preliminary results show that this locallyadaptive texture analysis algorithm, in conjunction with logistic regression, can predict the likelihood of false-positive biopsy with an ROC performance value of AUC=0.92 (p<0.001) with a 95% confidence interval [0.77, 0.94]. Significant texture feature predictors (p<0.05) included contrast, sum variance and difference average. Sensitivity for false-positives was 51% at the 100% cancer detection operating point. Although preliminary, clinical implications of using prediction models incorporating these texture features may include the future development of better tools and guidelines regarding personalized breast cancer screening recommendations. Further studies are warranted to prospectively validate our findings in larger screening populations and evaluate their clinical utility.

  17. Inhibition of Cdk2 activity decreases Aurora-A kinase centrosomal localization and prevents centrosome amplification in breast cancer cells.

    PubMed

    Leontovich, Alexey A; Salisbury, Jeffrey L; Veroux, Massimiliano; Tallarita, Tiziano; Billadeau, Daniel; McCubrey, James; Ingle, James; Galanis, Evanthia; D'Assoro, Antonino B

    2013-05-01

    Centrosome amplification plays a key role in the origin of chromosomal instability (CIN) during cancer development and progression. In this study, MCF-7 breast cancer cell lines harboring abrogated p53 function (vMCF-7DNp53) were employed to investigate the relationship between induction of genotoxic stress, activation of cyclin-A/Cdk2 and Aurora-A oncogenic signalings and development of centrosome amplification. Introduction of genotoxic stress in the vMCF-7DNp53 cell line by treatment with hydroxyurea (HU) induced centrosome amplification that was mechanistically linked to Aurora-A kinase activity. In cells carrying defective p53, the development of centrosome amplification also occurred following treatment with another DNA damaging agent, methotrexate. Importantly, we demonstrated that Aurora-A kinase-induced centrosome amplification was mediated by Cdk2 kinase since molecular inhibition of Cdk2 activity by SU9516 suppressed Aurora-A centrosomal localization and consequent centrosome amplification. In addition, we employed vMCF-7DRaf-1 cells that display high levels of endogenous cyclin-A and demonstrated that molecular targeting of Aurora-A by Alisertib reduces cyclin-A expression. Taken together, these findings demonstrate a novel positive feed-back loop between cyclin-A/Cdk2 and Aurora-A pathways in the development of centrosome amplification in breast cancer cells. They also provide the translational rationale for targeting 'druggable cell cycle regulators' as an innovative therapeutic strategy to inhibit centrosome amplification and CIN in breast tumors resistant to conventional chemotherapeutic drugs.

  18. Decrease social inequalities return-to-work: development and design of a randomised controlled trial among women with breast cancer

    PubMed Central

    2014-01-01

    Background Despite the improvement in the care management, women cancer patients who are still in employment find themselves for the most part obliged to stop working while they are having treatment. Their return-to-work probability is impacted by numerous psychosocial factors. The objective is to describe the development and the content of an intervention aimed to facilitate the return to work of female breast cancer patients and in particular the women in the most precarious situations through early active individualised psychosocial support (APAPI). Methods The intervention proposed is made up of 4 interviews with a psychologist at the hospital, distributed over the year according to the diagnosis and conducted on the same day as a conventional follow-up consultation, then a consultation with a specialist job retention physician. We expect, in the first instance, that this intervention will reduce the social inequalities of the return-to-work rate at 12 months. The EPICES score will enable the population to be broken down according to the level of social precariousness. The other expected results are the reduction of the social inequalities in the quality of the return to work at 18 and 24 months and the disparities between the individual and collective resources of the patients. This intervention is assessed in the context of a controlled and randomised multi-centre study. The patients eligible are women aged between 18 and 55 years with a unilateral breast cancer with local extension exclusively, having received surgery followed by adjuvant chemotherapy, in employment at the time of the diagnosis and dealt with by one of the 2 investigating centres. Discussion It is essential to assess this type of intervention before envisaging its generalisation. The study set in place will enable us to measure the impact of this intervention aiming to facilitate the return to work of breast cancer patients, in particular for those who suffer from social fragility

  19. Cochinchina momordica seed extract induces G2/M arrest and apoptosis in human breast cancer MDA-MB-231 cells by modulating the PI3K/Akt pathway.

    PubMed

    Meng, Lin-Yi; Liu, Hong-Rui; Shen, Yang; Yu, Yun-Qiu; Tao, Xia

    2011-01-01

    Cochinchina momordica seeds are a kind of traditional Chinese herb. In this study, anticancer activity and underlying mechanisms were investigated with an extract using human breast cancer MDA-MB-231 cells. The survival rate was reduced in a concentration- and time-dependent manner as assessed by MTT assay. After incubation for 48 h, typical apoptotic morphological changes were observed by Hoechst 33258 dye assay. Flow cytometry revealed that the treatment obviously induced G2/M arrest and apoptosis in MDA-MB-231 cells. Furthermore, western blotting demonstrated downregulation of protein expression of PI3K, Akt, NF-kB, Bcl-2, Cdk1 and cyclin B1, whereas Bax and caspase-3 were upregulated. Our results suggest that the extract induced cell cycle G2/M arrest and apoptosis in MDA-MB-231 cells by decreasing PI3K/Akt pathway. Therefore, we propose that ECMS has potential as a breast cancer chemotherapeutic agent.

  20. Color edges extraction using statistical features and automatic threshold technique: application to the breast cancer cells

    PubMed Central

    2014-01-01

    Background Color image segmentation has been so far applied in many areas; hence, recently many different techniques have been developed and proposed. In the medical imaging area, the image segmentation may be helpful to provide assistance to doctor in order to follow-up the disease of a certain patient from the breast cancer processed images. The main objective of this work is to rebuild and also to enhance each cell from the three component images provided by an input image. Indeed, from an initial segmentation obtained using the statistical features and histogram threshold techniques, the resulting segmentation may represent accurately the non complete and pasted cells and enhance them. This allows real help to doctors, and consequently, these cells become clear and easy to be counted. Methods A novel method for color edges extraction based on statistical features and automatic threshold is presented. The traditional edge detector, based on the first and the second order neighborhood, describing the relationship between the current pixel and its neighbors, is extended to the statistical domain. Hence, color edges in an image are obtained by combining the statistical features and the automatic threshold techniques. Finally, on the obtained color edges with specific primitive color, a combination rule is used to integrate the edge results over the three color components. Results Breast cancer cell images were used to evaluate the performance of the proposed method both quantitatively and qualitatively. Hence, a visual and a numerical assessment based on the probability of correct classification (P C ), the false classification (P f ), and the classification accuracy (Sens(%)) are presented and compared with existing techniques. The proposed method shows its superiority in the detection of points which really belong to the cells, and also the facility of counting the number of the processed cells. Conclusions Computer simulations highlight that the proposed method

  1. Breast Cancer Survival among African-Americans Living in the Midwest: Disparities and Recommendations to Decrease Mortality.

    PubMed

    Hill, Jackie; Watanabe-Galloway, Shinobu; Shostrom, Valerie; Nsiah-Kumi, Phyllis

    2015-07-01

    Socioeconomic status is highly correlated with breast cancer risk and outcomes. Omaha, Nebraska has the third highest African-American poverty rate of the 100 largest U.S. metropolitan areas. Access to healthcare is a major issue in this community. This study analyzed the state cancer registry data to establish a baseline for breast cancer survivorship among African-American women in Nebraska. Specifically, the study examined the 5-year survivorship difference between African-American women and White women and the factors associated with poor survival. It was found that the 5-year survival rate for African-American women was 43% compared to 75% for White women and that this disparity persisted after taking into consideration the staging differences. The multivariable analysis results indicated that in addition to being African-American, increasing age, late-stage diagnosis, and lower socioeconomic status were factors independently associated with reduced survival in this sample. Because of the younger age at diagnosis among African-American women, we recommend that health promotion and educational programs be directed toward younger women. A significantly larger proportion of African-Americans being diagnosed at a late stage also underscores the importance of education of women of all ages. Future research should examine quality and timing of treatment as well as comorbidity issues affecting African-American women.

  2. Acetylation-defective mutants of Pparγ are associated with decreased lipid synthesis in breast cancer cells

    PubMed Central

    Tian, Lifeng; Wang, Chenguang; Hagen, Fred K.; Gormley, Michael; Addya, Sankar; Soccio, Raymond; Casimiro, Mathew C.; Zhou, Jie; Powell, Michael J.; Xu, Ping; Deng, Haiteng; Sauve, Anthony A.; Pestell, Richard G.

    2014-01-01

    In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was confirmed by in vitro deacetylation assay. An in vivo labeling assay revealed K154/K155 as bona fide acetylation sites. The conserved acetylation sites of Pparγ1 and the catalytic domain of SIRT1 are both required for the interaction between Pparγ1 and SIRT1. Sirt1 and Pparγ1 converge to govern lipid metabolism in vivo. Acetylation-defective mutants of Pparγ1 were associated with reduced lipid synthesis in ErbB2 overexpressing breast cancer cells. Together, these results suggest that the conserved lysyl residues K154/K155 of Pparγ1 are acetylated and play an important role in lipid synthesis in ErbB2-positive breast cancer cells. PMID:25229978

  3. Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.

    PubMed

    Yu, Pan; Guo, Yawen; Yusufu, Maimaiti; Liu, Zeming; Wang, Shan; Yin, Xingjie; Peng, Gongling; Wang, Longqiang; Zhao, Xiangwang; Guo, Hui; Huang, Tao; Liu, Chunping

    2016-10-01

    EZH2, the catalytic subunit of polycomb repressor complex 2, has oncogenic properties, whereas RASSF2A, a Ras association domain family protein, has a tumor suppressor role in many types of human cancer. However, the interrelationship between these two genes remains unclear. Here, we showed that the downregulation of EZH2 reduces CpG island methylation of the RASSF2A promoter, thereby leading to increased RASSF2A expression. Our findings also showed that knockdown of EZH2 increased RASSF2A expression in the human breast cancer cell line MCF-7 in cooperation with DNMT1. This was similar to the effect of 5-Aza-CdR, a DNA methylation inhibitor that reactivates tumor suppressor genes and activated RASSF2A expression in our study. The EZH2 inhibitor DZNep markedly suppressed the proliferation, migration, and invasion of MCF-7 cells treated with ADR and TAM. EZH2 inhibits the expression of tumor suppressor gene RASSF2A via promoter hypermethylation. Thus, it plays an important role in tumorigenesis and is a potential therapeutic target for the treatment of breast cancer. © 2016 The Authors. Cell Biology International Published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology.

  4. Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse

    PubMed Central

    Jain, S.; Cohen, J.; Ward, M. M.; Kornhauser, N.; Chuang, E.; Cigler, T.; Moore, A.; Donovan, D.; Lam, C.; Cobham, M. V.; Schneider, S.; Hurtado Rúa, S. M.; Benkert, S.; Mathijsen Greenwood, C.; Zelkowitz, R.; Warren, J. D.; Lane, M. E.; Mittal, V.; Rafii, S.; Vahdat, L. T.

    2013-01-01

    Background Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. This study explores the effect of tetrathiomolybdate (TM), an anti-angiogenic copper chelator, on EPCs in patients at high risk for breast cancer recurrence. Patients and methods This phase 2 study enrolled breast cancer patients with stage 3 and stage 4 without evidence of disease (NED), and stage 2 if triple-negative. TM 100 mg orally was administered to maintain ceruloplasmin <17 mg/dl for 2 years or until relapse. The primary end point was change in EPCs. Results Forty patients (28 stage 2/3, 12 stage 4 NED) were enrolled. Seventy-five percent patients achieved the copper depletion target by 1 month. Ninety-one percent of triple-negative patients copper-depleted compared with 41% luminal subtypes. In copper-depleted patients only, there was a significant reduction in EPCs/ml by 27 (P = 0.04). Six patients relapsed while on study, of which only one patient had EPCs maintained below baseline. The 10-month relapse-free survival was 85.0% (95% CI 74.6%–96.8%). Only grade 3/4 toxicity was hematologic: neutropenia (3.1% of cycles), febrile neutropenia (0.2%), and anemia (0.2%). Conclusions TM is safe and appears to maintain EPCs below baseline in copper-depleted patients. TM may promote tumor dormancy and ultimately prevent relapse. PMID:23406736

  5. Tetrathiomolybdate-associated copper depletion decreases circulating endothelial progenitor cells in women with breast cancer at high risk of relapse.

    PubMed

    Jain, S; Cohen, J; Ward, M M; Kornhauser, N; Chuang, E; Cigler, T; Moore, A; Donovan, D; Lam, C; Cobham, M V; Schneider, S; Hurtado Rúa, S M; Benkert, S; Mathijsen Greenwood, C; Zelkowitz, R; Warren, J D; Lane, M E; Mittal, V; Rafii, S; Vahdat, L T

    2013-06-01

    Bone marrow-derived endothelial progenitor cells (EPCs) are critical for metastatic progression. This study explores the effect of tetrathiomolybdate (TM), an anti-angiogenic copper chelator, on EPCs in patients at high risk for breast cancer recurrence. This phase 2 study enrolled breast cancer patients with stage 3 and stage 4 without evidence of disease (NED), and stage 2 if triple-negative. TM 100 mg orally was administered to maintain ceruloplasmin <17 mg/dl for 2 years or until relapse. The primary end point was change in EPCs. Forty patients (28 stage 2/3, 12 stage 4 NED) were enrolled. Seventy-five percent patients achieved the copper depletion target by 1 month. Ninety-one percent of triple-negative patients copper-depleted compared with 41% luminal subtypes. In copper-depleted patients only, there was a significant reduction in EPCs/ml by 27 (P = 0.04). Six patients relapsed while on study, of which only one patient had EPCs maintained below baseline. The 10-month relapse-free survival was 85.0% (95% CI 74.6%-96.8%). Only grade 3/4 toxicity was hematologic: neutropenia (3.1% of cycles), febrile neutropenia (0.2%), and anemia (0.2%). TM is safe and appears to maintain EPCs below baseline in copper-depleted patients. TM may promote tumor dormancy and ultimately prevent relapse.

  6. Acetylation-defective mutant of Pparγ is associated with decreased lipid synthesis in breast cancer cells.

    PubMed

    Tian, Lifeng; Wang, Chenguang; Hagen, Fred K; Gormley, Michael; Addya, Sankar; Soccio, Raymond; Casimiro, Mathew C; Zhou, Jie; Powell, Michael J; Xu, Ping; Deng, Haiteng; Sauve, Anthony A; Pestell, Richard G

    2014-09-15

    In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was confirmed by in vitro deacetylation assay. An in vivo labeling assay revealed K154/K155 as bona fide acetylation sites. The conserved acetylation sites of Pparγ1 and the catalytic domain of SIRT1 are both required for the interaction between Pparγ1 and SIRT1. Sirt1 and Pparγ1 converge to govern lipid metabolism in vivo. Acetylation-defective mutants of Pparγ1 were associated with reduced lipid synthesis in ErbB2 overexpressing breast cancer cells. Together, these results suggest that the conserved lysyl residues K154/K155 of Pparγ1 are acetylated and play an important role in lipid synthesis in ErbB2-positive breast cancer cells.

  7. Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients.

    PubMed

    Karatas, Fatih; Erdem, Gokmen Umut; Sahin, Suleyman; Aytekin, Aydin; Yuce, Deniz; Sever, Ali R; Babacan, Taner; Ates, Ozturk; Ozisik, Yavuz; Altundag, Kadri

    2017-04-01

    The relation between higher body mass index (BMI) and pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer (BC) is a controversial issue according to the data of Western and Asian patients. The aim of this study is to evaluate BMI and pCR to NAC and discuss the importance of pCR outcomes in Turkish BC patients as a bridging country between Europe and Asia. Of the 4423 BC patients diagnosed between the years 1994 and 2015 in Hacettepe University Cancer Institute, 295 female patients with stage II and III BC were enrolled in the study. Three different group divisions were done according to patients' BMI as normal or underweight (N/U) patients (BMI <25 kg/m(2)), overweight (OW) patients (BMI = 25-29.9 kg/m(2)) and obese (OB) patients (BMI ≥30 kg/m(2)). BC subtypes were defined as luminal-like (ER/PR-positive and HER2-negative), HER2/luminal (ER/PR-positive and HER2-positive), HER2-type (ER/PR-negative and HER2-positive), and triple-negative (TNBC; ER/PR- and HER2-negative). The analysis of overall survival (OS) and recurrence-free survival (RFS) was performed according to Kaplan-Meier method. The Log-rank test was used to compare the subgroup analysis and logistic regression analysis to determine the independent prognostic factors. In this study, a total number of 93 (31.5%) patients were N/U, 107 (36.3%) patients were OW and 95 (32.2%) patients were OB. Among groups, except for the age, no baseline clinicopathological differences were found. In 70 (23.7%) patients, pCR was achieved. pCR rates in N/U, OW and OB were 31.2%, 22.4%, and 17.9% respectively, showing a considerable trend towards significance (P = 0.09 in chi-square test). In the multivariate logistic regression analysis, obesity was an independent adverse prognostic feature on pCR to NAC compared to N/U patients (OR, 0.34; 95% CI, 0.13 to 0.85, P = 0.02). The recurrence rates were slightly increased with the increase of BMI (N/U = 24.7%, OW = 29.0% and OB

  8. Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration.

    PubMed

    Brooker, Sonja; Martin, Susan; Pearson, Ann; Bagchi, Debasis; Earl, Judith; Gothard, Lone; Hall, Emma; Porter, Lucy; Yarnold, John

    2006-04-01

    Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n = 44) or placebo (n = 22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm(2)) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. At 12 months post-randomisation, > or =50% reduction in surface area (cm(2)) of breast induration was recorded in 13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. The study failed to show efficacy of orally-administered GSPE in patients with breast induration following radiotherapy for breast cancer.

  9. Can internal mammary chain treatment decrease the risk of death for patients with medial breast cancers and positive axillary lymph nodes

    SciTech Connect

    Le, M.G.; Arriagada, R.; de Vathaire, F.; Dewar, J.; Fontaine, F.; Lacour, J.; Contesso, G.; Tubiana, M. )

    1990-12-01

    The effect of internal mammary chain treatment on each type of malignant death-related event was analyzed in 1195 patients with operable breast cancer and histologically involved axillary lymph nodes. A group of 135 patients who had no internal mammary chain treatment was compared with a control group of 1060 patients who were treated by surgery and/or postoperative radiation therapy. In a multivariate analysis taking into account age, clinical size of the tumor, histoprognostic grading, and the number of positive axillary lymph nodes, quantitative interaction tests were used to determine whether the effects of internal mammary chain treatment on each type of malignant event were significantly different for patients with a lateral tumor compared with those with a medial tumor. The authors found that the effects of this treatment on the risks of distant metastases and of secondary breast cancer were not the same for the patients with a medial tumor as for those with a lateral tumor. For the untreated patients with a medial tumor, the risks of distant metastases and second breast cancer were, respectively, 1.6 (P = 0.02) and 2.9 (P = 0.02), compared with the treated patients. Conversely, for women with lateral tumor, no difference between the two treatment groups was observed. Thus, internal mammary chain treatment may improve long-term survival rate in patients with a medial tumor and positive axillary lymph nodes essentially by decreasing the risk of development of distant metastases (mainly brain, distant lymph nodes, multiple simultaneous metastases) and/or a secondary breast cancer.

  10. A maternal high n-6 fat diet with fish oil supplementation during pregnancy and lactation in rats decreases breast cancer risk in the female offspring.

    PubMed

    Su, Hui-Min; Hsieh, Pei-Hsuan; Chen, Hui-Feng

    2010-11-01

    The timing of dietary fat intake may modify breast cancer risk. In addition, n-3 fatty acids reduce, and n-6 fatty acids increase, the risk of breast cancer and a maternal high n-6 fat diet results in a greater risk of breast cancer in the female offspring. We hypothesized that the timing of n-3 fatty acid-enriched fish oil supplementation would be important for reducing the risk of breast cancer. Female rats were fed to a high n-6 fat diet containing 20% of the sunflower oil by weight during pregnancy and lactation, and the female offspring were exposed to fish oil by oral gavage either during the perinatal period via maternal intake or during puberty or adulthood. Exposure during the perinatal period to a maternal high n-6 fat diet with fish oil supplementation significantly reduced the incidence of carcinogen-induced mammary tumors in the female offspring compared to a maternal high n-6 fat diet with no fish oil supplementation or fish oil supplementation later in life (P=.0228 by Cox proportional hazards model). We found that a maternal high n-6 fat diet during pregnancy is more important in increasing the risk of mammary tumors in the female offspring than a maternal high n-6 fat diet during lactation. This study suggests that fish oil supplementation during the perinatal period decreases the effect of a maternal high n-6 fat diet on subsequent carcinogen-induced mammary tumor risk, whereas fish oil supplementation during puberty or adulthood does not. Copyright © 2010 Elsevier Inc. All rights reserved.

  11. Green tea aqueous extract reduces visceral fat and decreases protein availability in rats fed with a high-fat diet.

    PubMed

    Bajerska, Joanna; Wozniewicz, Małgorzata; Jeszka, Jan; Drzymala-Czyz, Slawomira; Walkowiak, Jaroslaw

    2011-02-01

    Green tea is associated with beneficial health effects mainly because of its body fat-reducing and hypocholesterolemic activities, but an effective dose without pronounced influence on protein availability is unknown. The objective of this study was to examine the hypothesis that green tea aqueous extract (GTAE) depending on dose improves cardiovascular risk indicators such as body weight, visceral fat content, and atherogenic index of plasma and does not have unfavorable effect on protein availability in rats fed with a high-fat diet. The rats fed with a high-fat diet enriched with 1.1 and 2.0% GTAE for 8 weeks had significantly (P < .05) lower atherogenic index (in both groups, about 14.3%). Only administration of 2.0% GTAE significantly (P < .05) decreased body weight gain (5.6%) and prevented visceral fat accumulation (17.8%) in rats. However, considerably (P < .05), reduction in the digestion of protein (but not fat) was observed in both GTAE groups (1.1% GTAE: 82.6% ± 1.8%; 2.0% GTAE: 84.3% ± 0.8%) when compared to the control (93.3% ± 1.5%). It was concluded that GTAE may have preventive effects on the accumulation of visceral fat but only in higher doses. Although both doses improved cardiovascular risk indicators, they, in addition, significantly inhibited protein digestion. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

    PubMed

    De, Soumita; Sen, Tuhinadri; Chatterjee, Mitali

    2015-11-01

    Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg(-1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

  13. Ivy leaves dry extract EA 575® decreases LPS-induced IL-6 release from murine macrophages.

    PubMed

    Schulte-Michels, J; Runkel, F; Gokorsch, S; Häberlein, H

    2016-03-01

    IL-6 plays a key role in the course of inflammatory processes as well as in the regulation of immune responses by the release of different cytokines. IL-6 is produced e.g. by macrophages recruited to the airways in response to a variety of inflammatory stimuli like allergens and respiratory viruses. Patients with inflammatory airway diseases therefore may benefit from therapies targeting the IL-6 pathway, e.g. reduction of the IL-6 release. Within this context, we tested the influence of the ivy leaves dry extract EA 575® on the LPS-induced release of IL-6 from murine macrophages (J774.2). One point seven µg/ml (5 µM) corticosterone served as positive control and was able to reduce LPS-induced IL-6 release by 46 ± 4%. EA 575® was tested in concentrations between 40 and 400 µg/ml. EA 575® decreased the LPS-induced IL-6 release in a dose-dependent manner and statistically significant by 25 ± 4%, 32 ± 4%, and 40 ± 7% in concentrations of 80, 160, and 400 µg/ml, respectively. The present data suggest an anti-inflammatory effect of EA 575® used in therapy of chronic- and acute inflammatory airway diseases accompanied with cough.

  14. Melinjo (Gnetum gnemon L.) Seed Extract Decreases Serum Uric Acid Levels in Nonobese Japanese Males: A Randomized Controlled Study

    PubMed Central

    Kanai, Yoshiaki; Katagiri, Mikiyuki; Mori, Akemi; Tatefuji, Tomoki

    2013-01-01

    Melinjo (Gnetum gnemon L.) seed extract (MSE) containing trans-resveratrol (3,5,4′-trihydroxy-trans-stilbene) and other derivatives exerts various beneficial effects. However, its mechanism of action in humans remains unknown. In this study, we aimed to investigate beneficial effects of MSE in healthy adult males. In this double-blind, randomized controlled study, 30 males aged 35–70 years with ≤10% flow-mediated dilatation received placebo or 750 mg MSE powder for 8 weeks, and twenty-nine males (45.1 ± 8.8 years old) completed the trial. There was a significant difference in the melinjo and placebo groups. Compared with the placebo control, MSE significantly reduced serum uric acid at 4 weeks and 8 weeks (n = 14 and 15, resp.). HDL cholesterol was significantly increased in the melinjo group. To clarify the mechanism of MSE for reducing uric acid, we investigated xanthine oxidase inhibitory activity, angiotensin II type 1 (AT1) receptor binding inhibition rate, and agonistic activities for PPARα and PPARγ. MSE, trans-resveratrol, and a resveratrol dimer, gnetin C (GC), significantly inhibit AT1 receptor binding and exhibit mild agonistic activities for PPARα and PPARγ. In conclusion, MSE may decrease serum uric acid regardless of insulin resistance and may improve lipid metabolism by increasing HDL cholesterol. PMID:24454499

  15. Evaluation of apoptotic activity of Withania coagulans methanolic extract against human breast cancer and Vero cell lines.

    PubMed

    Ahmad, Rumana; Fatima, Afreen; Srivastava, A N; Khan, Mohsin Ali

    The genus Withania (Family: Solanaceae) holds an important position in Ayurveda, the Indian traditional system of medicine. Withania somnifera Dunal and Withania coagulans Dunal have been documented in folklore as panaceas for various ailments since time immemorial. W. coagulans (WC), commonly called as Indian cheese maker is used for fermenting milk for cheese production in various parts of India. In the study, in vitro cytotoxicity of methanolic extract of dried fruits (berries) of WC was evaluated in a dose dependent manner using trypan blue dye exclusion method against human breast cancer cell line MDA-MB-231 and normal kidney epithelial cell line Vero in the range 20-200 μg/ml. The percentage viability of the cell lines was determined by using MTT assay and cytometry. Methanolic extract of WC showed significant anticancer activity against MDA-MB-231 cell line. Cell viability was reduced to about 50% at 40 μg/ml of methanolic extract in 50% DMSO. Cytotoxicity of the extract was lower in 10% and 1% DMSO. On the other hand, methanolic extract of WC did not exhibit any significant in vitro activity against Vero cells at 170 and 200 μg/ml. AGE of isolated DNA from treated cancer cells revealed characteristic ladder like fragmentation, a hallmark of apoptosis. HPLC profiling was carried out for identification of the active components, which demonstrated the presence of Withaferin A in the methanolic extract. Methanolic extract of WC possesses apoptotic activity against human breast cancer cells in vitro albeit lower in comparison to W. somnifera and warrants further investigation. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  16. Antiproliferative activity of brown Cuban propolis extract on human breast cancer cells.

    PubMed

    Popolo, Ada; Piccinelli, Lisa Anna; Morello, Silvana; Cuesta-Rubio, Osmany; Sorrentino, Rosalinda; Rastrelli, Luca; Pinto, Aldo

    2009-12-01

    Brown Cuban propolis (BCP) is the major type of propolis in Cuba; its chemical composition is exclusive and the principal component is nemorosone. In this study we investigated the antiproliferative activity of the ethanol extract of BCP on human breast cancer cell lines. The MTT assay showed a significant antiproliferative activity (P<0.005) of BCP on MCF-7 (estrogen receptor positive ER+) rather than MDA-MB 23 1 (ER-). This effect was concentration- (1-25 microg/mL) and time- (24-48 h) dependent, but it is only partially attributable to apoptosis. Indeed, our data showed that BCP administration to MCF-7 caused a significant (P>0.01) inhibition of cell growth in the G1 phase of cell cycle, which was mechanism dose- and time-dependent. 17-beta Estradiol (10 nM) administration to MCF-7 caused a significant (P<0.001), but not total reduction of BCP antiproliferative activity at concentrations of 1, 5 and 10 microg/mL, but not at the highest concentration (25 microg/mL). The coadministration of ICI 182,780 (100 nM), an antagonist of ER, on MCF-7 totally reduced the effect of BCP at 24 h, and showed a significant (P<0.001) reduction of BCP antiproliferative activity at 48 h. Thus it was hypothesized that BCP possesses an estrogen-like activity. It is to be noted, however, that BCP application to MDA-MB 23 1 at 48 h also induced increased cell mortality. Thus, it cannot be ruled out that BCP could not only interact with the ER, but also have an ER-independent activity.

  17. Linear classifier and textural analysis of optical scattering images for tumor classification during breast cancer extraction

    NASA Astrophysics Data System (ADS)

    Eguizabal, Alma; Laughney, Ashley M.; Garcia Allende, Pilar Beatriz; Krishnaswamy, Venkataramanan; Wells, Wendy A.; Paulsen, Keith D.; Pogue, Brian W.; López-Higuera, José M.; Conde, Olga M.

    2013-02-01

    Texture analysis of light scattering in tissue is proposed to obtain diagnostic information from breast cancer specimens. Light scattering measurements are minimally invasive, and allow the estimation of tissue morphology to guide the surgeon in resection surgeries. The usability of scatter signatures acquired with a micro-sampling reflectance spectral imaging system was improved utilizing an empirical approximation to the Mie theory to estimate the scattering power on a per-pixel basis. Co-occurrence analysis is then applied to the scattering power images to extract the textural features. A statistical analysis of the features demonstrated the suitability of the autocorrelation for the classification of notmalignant (normal epithelia and stroma, benign epithelia and stroma, inflammation), malignant (DCIS, IDC, ILC) and adipose tissue, since it reveals morphological information of tissue. Non-malignant tissue shows higher autocorrelation values while adipose tissue presents a very low autocorrelation on its scatter texture, being malignant the middle ground. Consequently, a fast linear classifier based on the consideration of just one straightforward feature is enough for providing relevant diagnostic information. A leave-one-out validation of the linear classifier on 29 samples with 48 regions of interest showed classification accuracies of 98.74% on adipose tissue, 82.67% on non-malignant tissue and 72.37% on malignant tissue, in comparison with the biopsy H and E gold standard. This demonstrates that autocorrelation analysis of scatter signatures is a very computationally efficient and automated approach to provide pathological information in real-time to guide surgeon during tissue resection.

  18. Ethanol extract of Brazilian red propolis induces apoptosis in human breast cancer MCF-7 cells through endoplasmic reticulum stress.

    PubMed

    Kamiya, Tetsuro; Nishihara, Hiroko; Hara, Hirokazu; Adachi, Tetsuo

    2012-11-07

    Propolis, a natural product collected from plants by honey bees, is commonly used in folk medicines. Endoplasmic reticulum (ER) stress is known to induce apoptosis through the induction of CCAAT/enhancer-binding protein homologous protein (CHOP). Here, we investigated whether ethanol extracts of propolis and caffeic acid phenethyl ester (CAPE) induce apoptosis, mitochondrial dysfunction, and ER stress in human breast cancer MCF-7 cells and human fibroblasts. Among several ethanol extracts of propolis and CAPE, Brazilian red propolis (BRP) significantly reduced MCF-7 cell viability through the induction of mitochondrial dysfunction, caspase-3 activity, and DNA fragmentation but did not affect those of fibroblasts. Moreover, treatment with BRP significantly induced CHOP expression in MCF-7 cells compared to fibroblasts. Further, pretreatment with a chemical chaperone, 4-phenylbutyric acid, suppressed BRP-triggered MCF-7 cell death. Overall, we revealed that an ethanol extract of BRP induces MCF-7 cell apoptosis through, at least in part, ER stress-related signaling.

  19. Medicinal herbs as a potential strategy to decrease methane production by rumen microbiota: a systematic evaluation with a focus on Perilla frutescens seed extract.

    PubMed

    Wang, Jiakun; Liu, Mei; Wu, Yuelei; Wang, Liang; Liu, Jianxin; Jiang, Linshu; Yu, Zhongtang

    2016-11-01

    Mitigation of the methane (CH4) emission from ruminants is needed to decrease the environmental impact of ruminant animal production. Different plant materials and chemicals have been tested, but few are both effective and practical. Medicinal herbs contain biological compounds and antimicrobials that may be effective in lowering the CH4 production. However, few studies have systematically evaluated medicinal herbs for their effect on CH4 production or on the rumen microbiota. In this study, extracts from 100 medicinal herbs were assessed for their ability to decrease CH4 production by rumen microbiota in vitro. The extracts of 12 herbs effectively lowered the CH4 production, with the extract of Perilla frutescens seeds being the most effective. The major components of P. frutescens seed extract were identified, and the effects of the extract on the fermentation characteristics and populations of rumen methanogens, fungi, protozoa, and select bacteria were also assessed. The decreased CH4 production induced by the P. frutescens seed extract was accompanied by an increased abundance of Ruminobacter, Selenomonas, Succinivibrio, Shuttleworthis, Pseudobutyrivbrio, Anaerovibrio, and Roseomonas and a decreased abundance of Methanobrevibacter millerae. The abundance of Pedobacter, Anaeroplasma, Paludibacter, Ruminococcus, and unclassified Lachnospiraceae was positively correlated with the CH4 production, with no effects on volatile fatty acids. This study suggests that medicinal herbs may be used to mitigate the CH4 emission from ruminants.

  20. Freshwater clam extract supplementation improves wound healing by decreasing the tumor necrosis factor α level in blood.

    PubMed

    Peng, Yi-Chi; Fwu-LinYang; Subeq, Yi-Maun; Tien, Chin-Chieh; Lee, Ru-Ping

    2017-03-01

    The freshwater clam (Corbicula fluminea) is a widely consumed functional food in Asia and is traditionally used to improve health and either prevent or treat inflammation-related diseases. Numerous studies have proposed that freshwater clams act to prevent and attenuate inflammatory responses, and also serve as a possible inhibitor to systemic inflammation. However, there is limited information available about the effects of freshwater clams on wound healing. The present study investigated the influence of freshwater clam extract (FCE) on wound healing and inflammatory responses in a cutaneous incision model. Sixteen rats were used and divided into two groups: the FCE group and the normal saline (NS) group. The rats underwent dorsal full-thickness skin excisional wounds (diameter 20 × 10 mm). FCE or NS was administered for oral feeding twice daily for 14 days after wounding. Blood samples were taken and analyzed, and wound areas were measured at several time points during the 2 weeks after excision. On day 14 after wounding, skin biopsies from the wound sites were sent for histological examination. Treatment with FCE (71.63 ± 9.51 pg mL(-1) ) decreased tumor necrosis factor-α levels compared to the NS group (109.86 ± 12.55 pg mL(-1) ) after wounding at 3 h (P < 0.05). There were no significant differences in the levels of white blood cells, interleukin (IL)-6, or IL-10. The wound areas of the NS group (23.9%) were larger than those in the FCE group (8.26%) on day 14 (P < 0.05). Numerous fibroblasts and collagen fiber organization were observed in the FCE group. FCE supplementation improves the wound healing process. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  1. Gallotannin-rich Caesalpinia spinosa fraction decreases the primary tumor and factors associated with poor prognosis in a murine breast cancer model

    PubMed Central

    2013-01-01

    Background Several treatment alternatives are available for primary breast cancer, although those for metastatic disease or inflammation associated with tumor progression are ineffective. Therefore, there is a great need for new therapeutic alternatives capable of generating an immune response against residual tumor cells, thus contributing to eradication of micrometastases and cancer stem cells. The use of complex natural products is an excellent therapeutic alternative widely used by Chinese, Hindu, Egyptian, and ancestral Latin-American Indian populations. Methods The present study evaluated cytotoxic, antitumor, and tumor progression activities of a gallotannin-rich fraction derived from Caesalpinia spinosa (P2Et). The parameters evaluated in vitro were mitochondrial membrane depolarization, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and clonogenic activity. The parameters evaluated in vivo were tumor growth, leukocyte number, metastatic cell number, and cytokine production by flow cytometry. Results The in vitro results showed that the P2Et fraction induced apoptosis with mitochondrial membrane potential loss, phosphatidylserine externalization, caspase 3 activation, DNA fragmentation, and decreased clonogenic capacity of 4T1 cells. In vivo, the P2Et fraction induced primary tumor reduction in terms of diameter and weight in BALB/c mice transplanted with 4T1 cells and decreased numbers of metastatic cells, mainly in the spleen. Furthermore, decreases in the number of peripheral blood leukocytes (leukemoid reaction) and interleukin 6 (IL-6) serum levels were found, which are events associated with a poor prognosis. The P2Et fraction exerts its activity on the primary tumor, reduces cell migration to distant organs, and decreases IL-6 serum levels, implying tumor microenvironment mechanisms. Conclusions Overall, the P2Et fraction lessens risk factors associated with tumor progression and diminishes primary tumor size, showing

  2. Polyphenolic extract of InsP 5-ptase expressing tomato plants reduce the proliferation of MCF-7 breast cancer cells.

    PubMed

    Alimohammadi, Mohammad; Lahiani, Mohamed Hassen; McGehee, Diamond; Khodakovskaya, Mariya

    2017-01-01

    In recent years, by extensive achievements in understanding the mechanisms and the pathways affected by cancer, the focus of cancer research is shifting from developing new chemotherapy methods to using natural compounds with therapeutic properties to reduce the adverse effects of synthetic drugs on human health. We used fruit extracts from previously generated human type I InsP 5-ptase gene expressing transgenic tomato plants for assessment of the anti-cancer activity of established genetically modified tomato lines. Cellular assays (MTT, Fluorescent microscopy, Flow Cytometry analysis) were used to confirm that InsP 5-ptase fruit extract was more effective for reducing the proliferation of breast cancer cells compared to wild-type tomato fruit extract. Metabolome analysis of InsP 5-ptase expressing tomato fruits performed by LC-MS identified tomato metabolites that may play a key role in the increased anti-cancer activity observed for the transgenic fruits. Total transcriptome analysis of cancer cells (MCF-7 line) exposed to an extract of transgenic fruits revealed a number of differently regulated genes in the cells treated with transgenic extract compared to untreated cells or cells treated with wild-type tomato extract. Together, this data demonstrate the potential role of the plant derived metabolites in suppressing cell viability of cancer cells and further prove the potential application of plant genetic engineering in the cancer research and drug discovery.

  3. BZL101, a phytochemical extract from the Scutellaria barbata plant, disrupts proliferation of human breast and prostate cancer cells through distinct mechanisms dependent on the cancer cell phenotype.

    PubMed

    Marconett, Crystal N; Morgenstern, Travis J; San Roman, Adrianna K; Sundar, Shyam N; Singhal, Ankur K; Firestone, Gary L

    2010-08-15

    BZL101 is an aqueous extract from the Scutellaria barbata plant shown to have anticancer properties in a variety of human cancers. In order to determine its efficacy on human reproductive cancers, we assessed the responses of two human breast cancer cell lines, estrogen sensitive MCF7 and estrogen insensitive MDA-MB-231, and of two human prostate cancer cell lines, androgen sensitive LNCaP and androgen insensitive PC3 which are human cell lines that represent early and late stage reproductive cancers. BZL101 inhibited reproductive cancer growth in all cell lines by regulating expression levels of key cell cycle components that differ with respect to the cancer cell phenotypes. In early stage estrogen sensitive MCF7 cells, BZL101 induced a G₁ cell cycle arrest and ablated expression of key G₁ cell cycle regulators Cyclin D1, CDK2 and CDK4, as well as growth factor stimulatory pathways and estrogen receptor-α expression. Transfection of luciferase reporter plasmids revealed that the loss of CDK2, CDK4 and estrogen receptor-α transcript expression resulted from the BZL-dependent ablation of promoter activities. BZL101 growth arrests early stage androgen sensitive LNCaP cells in the G₂/M phase with corresponding decreases in Cyclin B1, CDK1 and androgen receptor expression. In late stage hormone insensitive breast (MDA-MB-231) and prostate (PC3) cancer cells, BZL101 induced an S phase arrest with corresponding ablations in Cyclin A2 and CDK2 expression. Our results demonstrate that BZL101 exerts phenotype specific anti-proliferative gene expression responses in human breast and prostate cancer cells, which will be valuable in the potential development of BZL-based therapeutic strategies for human reproductive cancers.

  4. Unsupervised feature construction and knowledge extraction from genome-wide assays of breast cancer with denoising autoencoders.

    PubMed

    Tan, Jie; Ung, Matthew; Cheng, Chao; Greene, Casey S

    2015-01-01

    Big data bring new opportunities for methods that efficiently summarize and automatically extract knowledge from such compendia. While both supervised learning algorithms and unsupervised clustering algorithms have been successfully applied to biological data, they are either dependent on known biology or limited to discerning the most significant signals in the data. Here we present denoising autoencoders (DAs), which employ a data-defined learning objective independent of known biology, as a method to identify and extract complex patterns from genomic data. We evaluate the performance of DAs by applying them to a large collection of breast cancer gene expression data. Results show that DAs successfully construct features that contain both clinical and molecular information. There are features that represent tumor or normal samples, estrogen receptor (ER) status, and molecular subtypes. Features constructed by the autoencoder generalize to an independent dataset collected using a distinct experimental platform. By integrating data from ENCODE for feature interpretation, we discover a feature representing ER status through association with key transcription factors in breast cancer. We also identify a feature highly predictive of patient survival and it is enriched by FOXM1 signaling pathway. The features constructed by DAs are often bimodally distributed with one peak near zero and another near one, which facilitates discretization. In summary, we demonstrate that DAs effectively extract key biological principles from gene expression data and summarize them into constructed features with convenient properties.

  5. Multiple effects of Xihuang pill aqueous extract on the Hs578T triple-negative breast cancer cell line

    PubMed Central

    Zheng, Wenxian; Han, Shuyan; Jiang, Shantong; Pang, Lina; Li, Xiaohong; Liu, Xijuan; Cao, Minhua; Li, Pingping

    2016-01-01

    The management of triple-negative breast cancer (TNBC) is challenging due to the aggressive behavior, lack of therapeutic options and relatively poor prognosis. Xihuang pill (XHP) is a well-known Traditional Chinese Medicine with anticancer activity. The aim of the present study was to investigate whether the aqueous extract of XHP (AEXHP) has anti-proliferative activity against the Hs578T TNBC cell line, and to elucidate its molecular mechanisms of action. First, an MTT assay was used to evaluate the anti-proliferative activity of AEXHP on the Hs578T cell line; furthermore, the cell cycle distribution, mitochondrial membrane potential and apoptotic rate were determined by flow cytometry, and western blot analysis was used to assess the expression of apoptosis and cell cycle regulatory proteins to investigate the mechanisms of action. The results revealed that the cell viability was significantly inhibited by AEXHP in a dose- and time-dependent manner. Apoptosis and mitochondrial membrane potential loss were detected, and after treatment with 4, 8 and 12 mg/ml AEXHP for 24 h, cleaved caspase-3 was 1.70-, 1.81- and 1.84-fold of that of the control, while procaspase-3, procaspase-8, cleaved caspase-8, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and the Bcl-2/Bax ratio were not significantly affected. Cell cycle analysis revealed that treatment with AEXHP led to S-phase arrest of Hs578T cells. Furthermore, AEXHP treatment resulted in decreased expression of cyclin A and cyclin dependent kinase 2 (CDK2), and increased expression of cyclin E and p21Cip1, as compared to the control group. In conclusion, the viability of Hs578T cells was significantly inhibited by AEXHP in a dose- and time-dependent manner, the likely mechanisms of which being induction of apoptosis, probably via the intrinsic, Bcl-2-independent pathway, and cell cycle arrest in S phase due to decreased expression of cyclin A and CDK2, and increased expression of cyclin E and p21Cip1. PMID

  6. Effects of Combined Soy Isoflavone Extract and Docetaxel Treatment on Murine 4T1 Breast Tumor Model

    PubMed Central

    Hejazi, Ehsan; Nasrollahzadeh, Javad; Fatemi, Ramina; Barzegar-Yar Mohamadi, Leila; Saliminejad, Kioomars; Amiri, Zohre; Kimiagar, Masoud; Houshyari, Mohammad; Tavakoli, Maryam; Idali, Farah

    2015-01-01

    Background Emergence of drug resistance has brought major problems in chemotherapy. Using nutrients in combination with chemotherapy could be beneficial for improvement of sensitivity of tumors to drug resistance. Soybean-derived isoflavones have been suggested as chemopreventive agents for certain types of cancer, particularly breast cancer. In this study, the synergistic effects of soy isoflavone extract in combination with docetaxel in murine 4T1 breast tumor model were investigated. Methods In this study, mice were divided into 4 groups (15 mice per group) of control, the dietary Soy Isoflavone Extract (SIE, 100 mg/kg diet), the Docetaxel (DOCE, 10 mg/kg) injection and the combination of dietary soy isoflavone extract and intravenous docetaxel injection (DOCE+SIE). After 3 injections of docetaxel (once a week), 7 mice were sacrificed to analyze MKI67 gene and protein expressions and the rest were monitored for diet consumption, tumor growth and survival rates. Results In DOCE+SIE group, diet consumption was significantly higher than DOCE group. While lifespan showed a trend towards improvement in DOCE+SIE group, no significant difference was observed among the 4 studied groups. Tumor volume was not significantly affected in treated groups. A lower but not significant MKI67 protein expression was detected in western blot in DOCE+SIE group. The mRNA expression was not significantly different among groups. Conclusion The results suggest that the combination of soy isoflavone as an adjunct to docetaxel chemotherapy can be effective in improving diet consumption in breast cancer. PMID:25926948

  7. Grape seed extract dose-responsively decreases disease severity in a rat model of mucositis; concomitantly enhancing chemotherapeutic effectiveness in colon cancer cells.

    PubMed

    Cheah, Ker Yeaw; Howarth, Gordon Stanley; Bastian, Susan Elaine Putnam

    2014-01-01

    Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Female Dark Agouti rats were gavaged with grape seed extract (400-1000 mg/kg) or water (day 3-11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. Compared with 5-Fluorouracil controls, grape seed extract (400-1000 mg/kg) significantly decreased the histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10-25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05) in Caco-2 cells and was more potent than 5-Fluorouracil at 50-100 µg/mL. Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells.

  8. Grape Seed Extract Dose-Responsively Decreases Disease Severity in a Rat Model of Mucositis; Concomitantly Enhancing Chemotherapeutic Effectiveness in Colon Cancer Cells

    PubMed Central

    Cheah, Ker Yeaw; Howarth, Gordon Stanley; Bastian, Susan Elaine Putnam

    2014-01-01

    Objective Mucositis is a serious disorder of the gastrointestinal tract that results from cancer chemotherapy. We investigated the effects of increasing grape seed extract doses on the severity of chemotherapy in a rat model and its coincident impact on chemotherapeutic effectiveness in colon cancer cells. Design Female Dark Agouti rats were gavaged with grape seed extract (400–1000 mg/kg) or water (day 3–11) and were injected intraperitoneally with 5-Fluorouracil (150 mg/kg) or saline (control) on day 9 to induce mucositis. Daily metabolic data were collected and rats were sacrificed on day 12. Intestinal tissues were collected for histological and myeloperoxidase analyses. Caco-2 cell viability was examined in response to grape seed extract in combination with 5-Fluorouracil by 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide) assay. Results Compared with 5-Fluorouracil controls, grape seed extract (400–1000 mg/kg) significantly decreased the histological damage score (P<0.05) in the jejunum. Grape seed extract (1000 mg/kg) increased jejunal crypt depth by 25% (P<0.05) in 5-Fluorouracil treated rats compared to 5-Fluorouracil controls, and attenuated the 5-Fluorouracil -induced reduction of mucosal thickness (25%, P<0.05). Grape seed extract (600 mg/kg) decreased myeloperoxidase activity by 55% (P<0.01) compared to 5-Fluorouracil controls. Grape seed extract was more effective at ameliorating 5-Fluorouracil induced intestinal injury, with effects most pronounced in the proximal jejunum. Grape seed extract (10–25 ug/mL) significantly enhanced the growth-inhibitory effects of 5-Fluorouracil by 26% (P<0.05) in Caco-2 cells and was more potent than 5-Fluorouracil at 50–100 µg/mL. Conclusion Grape seed extract may represent a new therapeutic option to decrease the symptoms of intestinal mucositis while concurrently impacting on the viability of colon cancer cells. PMID:24465501

  9. [Study on process and principle of lactose grinding modification to decrease hygroscopic of Rhodiolae Crenulatae Radix et Rhizoma extract].

    PubMed

    Zhang, Ding-Kun; Zhang, Fang; Lin, Jun-Zhi; Han, Li; Wu, Zhen-Feng; Yang, Ying-Guang; Yang, Ming

    2014-04-01

    In this paper, Rhodiolae Crenulatae Radix et Rhizoma extract,with high hygroscopic,was selected as research model, while lactose was selected as modifiers to study the effect of the grinding modification method on the hygroscopic. Subsequently, particle size distribution, scannin electron microscopy, infrared spectroscopy and surface properties were adopted for a phase analysis. The results showed that the modified extract, prepared by Rhodiolae Crenulatae Radix et Rhizoma extract grinding 5 min with the same amount of lactose UP2, which hygroscopic initial velocity, acceleration, and critical relative humidity moisture were less than that of Rhodiolae Crenulatae Radix et Rhizoma extract and the mixture dramatically. In addition, compared with the mixture, the size distribution of modified extract was much less, the microstructure was also difference, while the infrared spectroscopy and surface properties were similar with that of lactose. It is the main principle that lactose particle adhered to the surface of Rhodiolae Crenulatae Radix et Rhizoma extract after grinding mofication to decress the moisture obviously.

  10. Fatigue and gene expression in human leukocytes: increased NF-κB and decreased glucocorticoid signaling in breast cancer survivors with persistent fatigue.

    PubMed

    Bower, Julienne E; Ganz, Patricia A; Irwin, Michael R; Arevalo, Jesusa M G; Cole, Steve W

    2011-01-01

    Fatigue is highly prevalent in the general population and is one of the most common side effects of cancer treatment. There is growing evidence that pro-inflammatory cytokines play a role in cancer-related fatigue, although the molecular mechanisms for chronic inflammation and fatigue have not been determined. The current study utilized genome-wide expression microarrays to identify differences in gene expression and associated alterations in transcriptional activity in leukocytes from breast cancer survivors with persistent fatigue (n=11) and non-fatigued controls (n=10). We focused on transcription of inflammation-related genes, particularly those responsive to the pro-inflammatory NF-κB transcription control pathway. Further, given the role of glucocorticoids as key regulators of inflammatory processes, we examined transcription of glucocorticoid-responsive genes indicative of potential glucocorticoid receptor (GR) desensitization. Plasma levels of cortisol were also assessed. Consistent with hypotheses, results showed increased expression of transcripts with response elements for NF-κB, and reduced expression of transcripts with response elements for glucocorticoids (p<.05) in fatigued breast cancer survivors. No differences in plasma levels of cortisol were observed. These data indicate that increased activity of pro-inflammatory transcription factors may contribute to persistent cancer-related fatigue and provide insight into potential mechanisms for tonic increases in NF-κB activity, specifically decreased expression of GR anti-inflammatory transcription factors.

  11. Applying Data Mining Techniques to Extract Hidden Patterns about Breast Cancer Survival in an Iranian Cohort Study.

    PubMed

    Khalkhali, Hamid Reza; Lotfnezhad Afshar, Hadi; Esnaashari, Omid; Jabbari, Nasrollah

    2016-01-01

    Breast cancer survival has been analyzed by many standard data mining algorithms. A group of these algorithms belonged to the decision tree category. Ability of the decision tree algorithms in terms of visualizing and formulating of hidden patterns among study variables were main reasons to apply an algorithm from the decision tree category in the current study that has not studied already. The classification and regression trees (CART) was applied to a breast cancer database contained information on 569 patients in 2007-2010. The measurement of Gini impurity used for categorical target variables was utilized. The classification error that is a function of tree size was measured by 10-fold cross-validation experiments. The performance of created model was evaluated by the criteria as accuracy, sensitivity and specificity. The CART model produced a decision tree with 17 nodes, 9 of which were associated with a set of rules. The rules were meaningful clinically. They showed in the if-then format that Stage was the most important variable for predicting breast cancer survival. The scores of accuracy, sensitivity and specificity were: 80.3%, 93.5% and 53%, respectively. The current study model as the first one created by the CART was able to extract useful hidden rules from a relatively small size dataset.

  12. Identification of error making patterns in lesion detection on digital breast tomosynthesis using computer-extracted image features

    NASA Astrophysics Data System (ADS)

    Wang, Mengyu; Zhang, Jing; Grimm, Lars J.; Ghate, Sujata V.; Walsh, Ruth; Johnson, Karen S.; Lo, Joseph Y.; Mazurowski, Maciej A.

    2016-03-01

    Digital breast tomosynthesis (DBT) can improve lesion visibility by eliminating the issue of overlapping breast tissue present in mammography. However, this new modality likely requires new approaches to training. The issue of training in DBT is not well explored. We propose a computer-aided educational approach for DBT training. Our hypothesis is that the trainees' educational outcomes will improve if they are presented with cases individually selected to address their weaknesses. In this study, we focus on the question of how to select such cases. Specifically, we propose an algorithm that based on previously acquired reading data predicts which lesions will be missed by the trainee for future cases (i.e., we focus on false negative error). A logistic regression classifier was used to predict the likelihood of trainee error and computer-extracted features were used as the predictors. Reader data from 3 expert breast imagers was used to establish the ground truth and reader data from 5 radiology trainees was used to evaluate the algorithm performance with repeated holdout cross validation. Receiver operating characteristic (ROC) analysis was applied to measure the performance of the proposed individual trainee models. The preliminary experimental results for 5 trainees showed the individual trainee models were able to distinguish the lesions that would be detected from those that would be missed with the average area under the ROC curve of 0.639 (95% CI, 0.580-0.698). The proposed algorithm can be used to identify difficult cases for individual trainees.

  13. Changbai Mountain Ginseng (Panax ginseng C.A. Mey) Extract Supplementation Improves Exercise Performance and Energy Utilization and Decreases Fatigue-Associated Parameters in Mice.

    PubMed

    Ma, Guo-Dong; Chiu, Chun-Hui; Hsu, Yi-Ju; Hou, Chien-Wen; Chen, Yi-Ming; Huang, Chi-Chang

    2017-02-05

    Changbai Mountain Ginseng (CMG, Panax ginseng C.A. Mey) is a traditional medicine commonly found in Northeast China and grows at elevations of 2000 m or higher in the Changbai Mountain Range. CMG, considered to be a "buried treasure medicine", is priced higher than other types of ginseng. However, few studies have demonstrated the effects of CMG supplementation on exercise performance, physical fatigue, and the biochemical profile. The major compound of CMG extract was characterized by electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Male ICR mice were divided into 3 groups, the vehicle, CMG-1X and CMG-5X groups (n = 8 per group), and respectively administered 0, 5, or 25 mg/kg/day of CMG extract orally for four weeks. HPLC-ESI-MS/MS results showed that the major compound in CMG extract is ginsenoside Ro. CMG extract significantly increased muscle weight and relative muscle weight (%). CMG extract supplementation dose-dependently increased grip strength (p < 0.0001) and endurance swimming time, decreased levels of serum lactate (p < 0.0001), ammonia (p < 0.0001), creatine kinase (CK, p = 0.0002), and blood urea nitrogen (p < 0.0001), and economized glucose levels (p < 0.0001) after acute exercise challenge. The glycogen in the gastrocnemius muscle was significantly increased with CMG extract treatment. Biochemical profile results showed that creatinine and triacylglycerol significantly decreased and total protein and glucose increased with CMG treatment. This is the first report that CMG extract supplementation increases muscle mass, improves exercise performance and energy utilization, and decreases fatigue-associated parameters in vivo. The major component of CMG extract is ginsenoside Ro, which could be a potential bioactive compound for use as an ergogenic aid ingredient by the food industry.

  14. Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research

    PubMed Central

    Kienle, Gunver S; Glockmann, Anja; Schink, Michael; Kiene, Helmut

    2009-01-01

    Background Viscum album L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment. Methods Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality. Results 19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission

  15. Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats

    PubMed Central

    Sun, Wenyan; Yan, Chunhong; Frost, Bess; Wang, Xin; Hou, Chen; Zeng, Mengqi; Gao, Hongli; Kang, Yuming; Liu, Jiankang

    2016-01-01

    High blood pressure, or “hypertension,” is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension. PMID:27713551

  16. Protective effects of a freeze-dried extract of vegetables and fruits on the hydroxyl radical-mediated oxidative damage of DNA and decrease of erythrocytes deformability.

    PubMed

    Wang, Hsiao-Ning; Liu, Tsan-Zon; Chen, Ya-Lei; Shiuan, David

    2007-01-01

    The protective effects of a freeze-dried extracts of vegetables and fruits (BauYuan; BY) on the hydroxyl radical-mediated DNA strand breakages and the structural integrity of human red blood cells (RBCs) were investigated. First, the supercoiled plasmid (pEGFP-C1) DNA was subjected to oxidation damage by an ascorbate-fortified Fenton reaction and the protective effects were analyzed by agarose gel electrophoresis. In the absence of BY extracts, exposure of the high-throughput .OH-generating system (Fe2+ concentration >1.0 microM) caused a complete fragmentation of DNA. Supplementation of BY extract (1 mg/mL) to the plasmid DNA prior to the exposure could prevent it significantly. In contrast, as the plasmid exposed to a low-grade .OH-generating system (Fe2+<0.1 microM), the BY extract (1 mg/mL) provided an almost complete protection. Next, the cell deformabilities were measured to assess the protection effects of various BY extracts on human erythrocytes exposed to the oxidative insults. We found that both the aqueous extract and the organic solvent-derived extracts could strongly protect human RBCs from the reactive oxygen species (ROS)-mediated decrease in the deformability indices. The results implicated that the BY extracts could effectively protect the cell membrane integrity via scavenging ROS which enabling RBCs to maintain a balance of water content and surface area to prevent the drop of cell deformability.

  17. Optimized Protocol for Protein Extraction from the Breast Tissue that is Compatible with Two-Dimensional Gel Electrophoresis.

    PubMed

    Zakharchenko, Olena; Greenwood, Christina; Alldridge, Louise; Souchelnytskyi, Serhiy

    2011-03-10

    Proteomics is a highly informative approach to analyze cancer-associated transformation in tissues. The main challenge to use a tissue for proteomics studies is the small sample size and difficulties to extract and preserve proteins. The choice of a buffer compatible with proteomics applications is also a challenge. Here we describe a protocol optimized for the most efficient extraction of proteins from the human breast tissue in a buffer compatible with two-dimensional gel electrophoresis (2D-GE). This protocol is based on mechanically assisted disintegration of tissues directly in the 2D-GE buffer. Our method is simple, robust and easy to apply in clinical practice. We demonstrate high quality of separation of proteins prepared according to the reported here protocol.

  18. Levels of Vitamin E Decreases and Retinol Increases in Oil Extracts from Aged Alaska Pollock (Theragra chalcogramma) By-Products

    USDA-ARS?s Scientific Manuscript database

    The Alaska Pollock constitutes one of the largest commercial fish catch and generation of by-products in the world. Crude oil is one of the products generated from the by-products; however, quality loss is expected if time delay or temperature abuse is encountered before oil extraction. The objectiv...

  19. A low dose of droperidol decreases the desflurane concentration needed during breast cancer surgery: a randomized double-blinded study

    PubMed Central

    Adachi, Yushi U; Makita, Koshi

    2017-01-01

    Background Droperidol (DHB) reportedly reduces the dose of propofol needed to achieve hypnosis when anesthesia is induced and decreases the bispectral index (BIS) in propofol-sedated patients during spinal anesthesia. We reported previously that supplemental DHB decreased the BIS after the administration of sevoflurane and remifentanil. This study investigated the effect of DHB on desflurane (DES) consumption in a clinical setting. Methods We conducted a prospective, randomized double-blinded study of 35 women with American Society of Anesthesiologist physical status I or II who underwent a mastectomy. Either DHB (20 µg/kg) or a saline placebo was administered to patients 30 min after the induction of anesthesia. A blinded anesthesiologist maintained a BIS value of 50 during anesthesia by modulating inhaled DES concentrations that changed 0.5% at 2.5 min intervals and maintained analgesia via the constant administration of remifentanil by referring to vital signs. The primary endpoint was the effect of DHB on DES consumption. The secondary endpoints included blood circulatory parameters, the time from the end of surgery to extubation, and discharge time between the groups. Results The characteristics of the patients did not differ between the groups. The DHB group used a mean of 27.2 ± 6.0 ml of DES compared with 41.4 ± 9.5 ml by the placebo group (P < 0.05). Conclusions A small dose of DHB reduced the DES concentration needed to maintain a BIS of 50. Our results show that DHB reduced the consumption of DES without adverse effects. PMID:28184263

  20. The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line.

    PubMed

    Riva, L; Coradini, D; Di Fronzo, G; De Feo, V; De Tommasi, N; De Simone, F; Pizza, C

    2001-01-01

    Uncaria tomentosa, also known as "Uña de gato", is a Rubiaceae species widely used in South-American folk medicine for the treatment of cancer, arthritis, gastritis and epidemic diseases. Extracts of the plant have been shown to possess cytostatic and anti-inflammatory activity as well as mutagenic and antimutagenic properties. However, to date no studies have been carried out to verify the direct antitumor activity of the extracts. The present study investigates the effects of some extracts and their chromatographic fractions from the bark of U. tomentosa on the growth of a human breast cancer cell line (MCF7). Our data indicated that, in addition to the antimutagenic activity, U. tomentosa extracts and fractions exert a direct antiproliferative activity on MCF7. The bioassay-directed fractionation from barks and leaves resulted in the isolation of two active fractions, which displayed an IC50 of 10 mg/ml and 20 mg/ml, respectively and an antiproliferative effect, with about 90% of inhibition at a concentration of 100 mg/ml.

  1. Tomatine-containing green tomato extracts inhibit growth of human breast, colon, liver, and stomach cancer cells.

    PubMed

    Friedman, Mendel; Levin, Carol E; Lee, Seung-Un; Kim, Hyun-Jeong; Lee, In-Seon; Byun, Jae-Oke; Kozukue, Nobuyuki

    2009-07-08

    Tomato plants ( Lycopersicon esculentum ) synthesize the glycoalkaloids dehydrotomatine and alpha-tomatine, possibly as a defense against bacteria, fungi, viruses, and insects. Six green and three red tomato extracts were investigated for their ability to induce cell death in human cancer and normal cells using a microculture tetrazolium (MTT) assay. Compared to untreated controls, the high-tomatine green tomato extracts strongly inhibited the following human cancer cell lines: breast (MCF-7), colon (HT-29), gastric (AGS), and hepatoma (liver) (HepG2), as well as normal human liver cells (Chang). There was little inhibition of the cells by the three low-tomatine red tomato extracts. Cell death induced by the pure glycoalkaloids dehydrotomatine and alpha-tomatine isolated from green tomatoes and characterized by HPLC, GC, and GC-MS, as well as their respective aglycones tomatidenol and tomatidine, was also evaluated. alpha-Tomatine was highly effective in inhibiting all of the cell lines. Dehydrotomatine, tomatidenol, and tomatidine had little, if any, effect on cell inhibition. The results show that the susceptibility to destruction varies with the nature of the alkaloid and plant extract and the type of cancer cell. These findings extend related observations on the anticarcinogenic potential of glycoalkaloids and suggest that consumers may benefit by eating not only high-lycopene red tomatoes but also green tomatoes containing glycoalkaloids. Possible mechanisms of the anticarcinogenic and other beneficial effects and the significance of the cited observations for breeding improved tomatoes and for the human diet are discussed.

  2. Effect of Neem Leaf Extract (Azadirachta indica) on c-Myc Oncogene Expression in 4T1 Breast Cancer Cells of BALB/c Mice

    PubMed Central

    Othman, Fauziah; Motalleb, Gholamreza; Lam Tsuey Peng, Sally; Rahmat, Asmah; Basri, Rusliza; Pei Pei, Chong

    2012-01-01

    Objective: Breast cancer is the most common cause of cancer-related deaths in women both worldwide and in Malaysia. Azadirachta indica (A. Juss), commonly known as neem, is one of the most versatile medicinal plants that has gained worldwide prominence due to its medicinal properties. However, the anticancer effect of ethanolic neem leaf extract against breast cancer has not been documented. The purpose of the present study is to investigate the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice. Materials and Methods: In this experimental study, A total of 48 female BALB/c mice were divided randomly into four groups of 12 mice per group: i.cancer control (CC) treated with 0.5% Tween 20 in PBS, ii. 0.5 µg/mL tamoxifen citrate (CT), iii. 250 mg/kg neem leaf extract (C250), and iv. 500 mg/kg neem leaf extract (C500). in situ reverse transcription polymerase chain reaction (in situ RT-PCR) was applied to evaluate suppression of c-Myc oncogene expression in breast cancer tissue. Results: The C500 group showed significant (p<0.05) suppression of c-Myc oncogene expression compared to the CC group. Conclusion: c-Myc was found to be down regulated under the effect of 500 mg/kg ethanolic neem leaf extract. PMID:23626938

  3. Effect of Neem Leaf Extract (Azadirachta indica) on c-Myc Oncogene Expression in 4T1 Breast Cancer Cells of BALB/c Mice.

    PubMed

    Othman, Fauziah; Motalleb, Gholamreza; Lam Tsuey Peng, Sally; Rahmat, Asmah; Basri, Rusliza; Pei Pei, Chong

    2012-01-01

    Breast cancer is the most common cause of cancer-related deaths in women both worldwide and in Malaysia. Azadirachta indica (A. Juss), commonly known as neem, is one of the most versatile medicinal plants that has gained worldwide prominence due to its medicinal properties. However, the anticancer effect of ethanolic neem leaf extract against breast cancer has not been documented. The purpose of the present study is to investigate the effect of neem leaf extract on c-Myc oncogene expression in 4T1 breast cancer BALB/c mice. In this experimental study, A total of 48 female BALB/c mice were divided randomly into four groups of 12 mice per group: i.cancer control (CC) treated with 0.5% Tween 20 in PBS, ii. 0.5 µg/mL tamoxifen citrate (CT), iii. 250 mg/kg neem leaf extract (C250), and iv. 500 mg/kg neem leaf extract (C500). in situ reverse transcription polymerase chain reaction (in situ RT-PCR) was applied to evaluate suppression of c-Myc oncogene expression in breast cancer tissue. The C500 group showed significant (p<0.05) suppression of c-Myc oncogene expression compared to the CC group. c-Myc was found to be down regulated under the effect of 500 mg/kg ethanolic neem leaf extract.

  4. Cytotoxic effect of Alpinia scabra (Blume) Náves extracts on human breast and ovarian cancer cells

    PubMed Central

    2013-01-01

    Background Alpinia scabra, locally known as 'Lengkuas raya’, is an aromatic, perennial and rhizomatous herb from the family Zingiberaceae. It is a wild species which grows largely on mountains at moderate elevations in Peninsular Malaysia, but it can also survive in the lowlands like in the states of Terengganu and Northern Johor. The present study reports the cytotoxic potential of A. scabra extracts from different parts of the plant. Methods The experimental approach in the present study was based on a bioassay-guided fractionation. The crude methanol and fractionated extracts (hexane, chloroform and water) from different parts of A. scabra (leaves, rhizomes, roots and pseudo stems) were prepared prior to the cytotoxicity evaluation against human ovarian (SKOV-3) and hormone-dependent breast (MCF7) carcinoma cells. The identified cytotoxic extracts were then subjected to chemical investigations in order to identify the active ingredients. A normal human lung fibroblast cell line (MRC-5) was used to determine the specificity for cancerous cells. The cytotoxic extracts and fractions were also subjected to morphological assessment, DNA fragmentation analysis and DAPI nuclear staining. Results The leaf (hexane and chloroform) and rhizome (chloroform) extracts showed high inhibitory effect against the tested cells. Ten fractions (LC1-LC10) were yielded after purification of the leaf chloroform extract. Fraction LC4 which showed excellent cytotoxic activity was further purified and resulted in 17 sub-fractions (VLC1-VLC17). Sub-fraction VLC9 showed excellent cytotoxicity against MCF7 and SKOV-3 cells but not toxic against normal MRC-5 cells. Meanwhile, eighteen fractions (RC1-RC18) were obtained after purification of the rhizome chloroform extract, of which fraction RC5 showed cytotoxicity against SKOV-3 cells with high selectivity index. There were marked morphological changes when observed using phase-contrast inverted microscope, DAPI nuclear staining and also DNA

  5. GK-1 peptide reduces tumor growth, decreases metastatic burden, and increases survival in a murine breast cancer model.

    PubMed

    Torres-García, D; Pérez-Torres, A; Manoutcharian, K; Orbe, U; Servín-Blanco, R; Fragoso, G; Sciutto, E

    2017-10-09

    GK-1 is a parasite-derived peptide adjuvant of 18 amino acid-length that enhances T-cell function and increases survival in B16-F10 melanoma tumor-bearing mice. This study was designed to evaluate in vivo the antitumor efficacy of GK-1 on 4T1 mouse mammary carcinoma. BALB/c mice with palpable primary tumors were weekly intravenously injected three times with saline solution or three different concentrations (10, 50, or 100μg per mouse) of GK-1. GK-1 significantly increased lifespan (p<0.0001) and reduced the primary tumor weight (p=0.014) and volume (p<0.0001) with respect to control mice, with no statistically significant differences among GK-1 doses. At the primary tumor, we found increased necrotic areas associated with a reduction in tumor mass, as well as an increase in the antitumor cytokine IL-12. Especially encouraging is the ability of GK-1 to reduce the number of lung metastasis (p=0.006) disregarding the dose used. The participation of IL-6 in metastasis development and the decreased levels of CCL-2, CCL-3, TNF-α, CXCL-9, GM-CSF, and b-FGF found in lungs of GK-1-treated mice is discussed. Our study supports the effectiveness of GK-1 as an antineoplastic agent that merits further exploration in combination with other therapeutic approaches in future translational studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Validation of natural language processing to extract breast cancer pathology procedures and results

    PubMed Central

    Wieneke, Arika E.; Bowles, Erin J. A.; Cronkite, David; Wernli, Karen J.; Gao, Hongyuan; Carrell, David; Buist, Diana S. M.

    2015-01-01

    Background: Pathology reports typically require manual review to abstract research data. We developed a natural language processing (NLP) system to automatically interpret free-text breast pathology reports with limited assistance from manual abstraction. Methods: We used an iterative approach of machine learning algorithms and constructed groups of related findings to identify breast-related procedures and results from free-text pathology reports. We evaluated the NLP system using an all-or-nothing approach to determine which reports could be processed entirely using NLP and which reports needed manual review beyond NLP. We divided 3234 reports for development (2910, 90%), and evaluation (324, 10%) purposes using manually reviewed pathology data as our gold standard. Results: NLP correctly coded 12.7% of the evaluation set, flagged 49.1% of reports for manual review, incorrectly coded 30.8%, and correctly omitted 7.4% from the evaluation set due to irrelevancy (i.e. not breast-related). Common procedures and results were identified correctly (e.g. invasive ductal with 95.5% precision and 94.0% sensitivity), but entire reports were flagged for manual review because of rare findings and substantial variation in pathology report text. Conclusions: The NLP system we developed did not perform sufficiently for abstracting entire breast pathology reports. The all-or-nothing approach resulted in too broad of a scope of work and limited our flexibility to identify breast pathology procedures and results. Our NLP system was also limited by the lack of the gold standard data on rare findings and wide variation in pathology text. Focusing on individual, common elements and improving pathology text report standardization may improve performance. PMID:26167382

  7. Validation of natural language processing to extract breast cancer pathology procedures and results.

    PubMed

    Wieneke, Arika E; Bowles, Erin J A; Cronkite, David; Wernli, Karen J; Gao, Hongyuan; Carrell, David; Buist, Diana S M

    2015-01-01

    Pathology reports typically require manual review to abstract research data. We developed a natural language processing (NLP) system to automatically interpret free-text breast pathology reports with limited assistance from manual abstraction. We used an iterative approach of machine learning algorithms and constructed groups of related findings to identify breast-related procedures and results from free-text pathology reports. We evaluated the NLP system using an all-or-nothing approach to determine which reports could be processed entirely using NLP and which reports needed manual review beyond NLP. We divided 3234 reports for development (2910, 90%), and evaluation (324, 10%) purposes using manually reviewed pathology data as our gold standard. NLP correctly coded 12.7% of the evaluation set, flagged 49.1% of reports for manual review, incorrectly coded 30.8%, and correctly omitted 7.4% from the evaluation set due to irrelevancy (i.e. not breast-related). Common procedures and results were identified correctly (e.g. invasive ductal with 95.5% precision and 94.0% sensitivity), but entire reports were flagged for manual review because of rare findings and substantial variation in pathology report text. The NLP system we developed did not perform sufficiently for abstracting entire breast pathology reports. The all-or-nothing approach resulted in too broad of a scope of work and limited our flexibility to identify breast pathology procedures and results. Our NLP system was also limited by the lack of the gold standard data on rare findings and wide variation in pathology text. Focusing on individual, common elements and improving pathology text report standardization may improve performance.

  8. Learning from Social Media: Utilizing Advanced Data Extraction Techniques to Understand Barriers to Breast Cancer Treatment

    PubMed Central

    Freedman, Rachel A.; Viswanath, Kasisomayajula; Vaz-Luis, Ines; Keating, Nancy L.

    2017-01-01

    Purpose Past examinations of breast cancer treatment barriers have typically included registry, claims-based and smaller survey studies. We examined treatment barriers using a novel, comprehensive, social media analysis of on-line, candid discussions about breast cancer. Methods Using an innovative toolset to search postings on social networks, message boards, patient communities, and topical sites, we performed a large-scale qualitative analysis. We examined the sentiments and barriers expressed about breast cancer treatments by internet users during 1 year (2/1/14-1/31/15). We categorized posts based on thematic patterns and examined trends in discussions by race/ethnicity (white/black/Hispanic) when this information was available. Results We identified 1,024,041 unique posts related to breast cancer treatment. Overall, 57% of posts expressed negative sentiments. Using machine learning software, we assigned treatment barriers for 387,238 posts (38%). Barriers included emotional (23% of posts), preferences and spiritual/religious beliefs (21%), physical (18%), resource (15%), health care perceptions (9%), treatment processes/duration (7%), and relationships (7%). Black and Hispanic (vs. white) users more frequently reported barriers related to health care perceptions, beliefs, and pre-diagnosis/diagnosis organizational challenges and fewer emotional barriers. Conclusions Using a novel analysis of diverse social media users, we observed numerous breast cancer treatment barriers that differed by race/ethnicity. Social media is a powerful tool, allowing use of real world data for qualitative research, capitalizing on the rich discussions occurring spontaneously on-line. Future research should focus on how to further employ and learn from this type of social intelligence research across all medical disciplines. PMID:27339067

  9. Learning from social media: utilizing advanced data extraction techniques to understand barriers to breast cancer treatment.

    PubMed

    Freedman, Rachel A; Viswanath, Kasisomayajula; Vaz-Luis, Ines; Keating, Nancy L

    2016-07-01

    Past examinations of breast cancer treatment barriers have typically included registry, claims-based, and smaller survey studies. We examined treatment barriers using a novel, comprehensive, social media analysis of online, candid discussions about breast cancer. Using an innovative toolset to search postings on social networks, message boards, patient communities, and topical sites, we performed a large-scale qualitative analysis. We examined the sentiments and barriers expressed about breast cancer treatments by Internet users during 1 year (2/1/14-1/31/15). We categorized posts based on thematic patterns and examined trends in discussions by race/ethnicity (white/black/Hispanic) when this information was available. We identified 1,024,041 unique posts related to breast cancer treatment. Overall, 57 % of posts expressed negative sentiments. Using machine learning software, we assigned treatment barriers for 387,238 posts (38 %). Barriers included emotional (23 % of posts), preferences and spiritual/religious beliefs (21 %), physical (18 %), resource (15 %), healthcare perceptions (9 %), treatment processes/duration (7 %), and relationships (7 %). Black and Hispanic (vs. white) users more frequently reported barriers related to healthcare perceptions, beliefs, and pre-diagnosis/diagnosis organizational challenges and fewer emotional barriers. Using a novel analysis of diverse social media users, we observed numerous breast cancer treatment barriers that differed by race/ethnicity. Social media is a powerful tool, allowing use of real-world data for qualitative research, capitalizing on the rich discussions occurring spontaneously online. Future research should focus on how to further employ and learn from this type of social intelligence research across all medical disciplines.

  10. Extracts of Artocarpus communis Decrease α-Melanocyte Stimulating Hormone-Induced Melanogenesis through Activation of ERK and JNK Signaling Pathways

    PubMed Central

    Fu, Yi-Tzu; Lee, Chiang-Wen; Ko, Horng-Huey; Yen, Feng-Lin

    2014-01-01

    Artocarpus communis is an agricultural plant that is also used in folk medicine to prevent skin diseases, including acne and dermatitis. Extracts of A. communis have been used to effectively inhibit melanogenesis; however, the antimelanogenesis mechanism of these extracts has not yet been investigated. The present study utilized a cell-free tyrosinase assay as well as α-melanocyte stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells, performed a cytotoxicity assay, and determined cellular melanin content to examine the effects of a methanolic extract of A. communis (ACM) and various organic partition fractions of A. communis on melanogenesis. In addition, we performed western blot analysis to elucidate the mechanism of their antimelanogenesis effect. Our results indicated that, except for the n-hexane extract, ACM and the various partition extracts at noncytotoxic concentrations effectively decreased melanin content and tyrosinase activity by downregulating microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP response element-binding protein (p-CREB). Moreover, ACM and the partition fractions activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and finally to decrease melanin production. In conclusion, we suggest that noncytotoxic concentrations of ACM and the various partition fractions may be useful as references for developing skin-lighting agents for use in medicines or cosmetics. PMID:24737988

  11. Extracts of Artocarpus communis decrease α-melanocyte stimulating hormone-induced melanogenesis through activation of ERK and JNK signaling pathways.

    PubMed

    Fu, Yi-Tzu; Lee, Chiang-Wen; Ko, Horng-Huey; Yen, Feng-Lin

    2014-01-01

    Artocarpus communis is an agricultural plant that is also used in folk medicine to prevent skin diseases, including acne and dermatitis. Extracts of A. communis have been used to effectively inhibit melanogenesis; however, the antimelanogenesis mechanism of these extracts has not yet been investigated. The present study utilized a cell-free tyrosinase assay as well as α-melanocyte stimulating hormone- (-MSH-) induced tyrosinase assay conducted in B16F10 cells, performed a cytotoxicity assay, and determined cellular melanin content to examine the effects of a methanolic extract of A. communis (ACM) and various organic partition fractions of A. communis on melanogenesis. In addition, we performed western blot analysis to elucidate the mechanism of their antimelanogenesis effect. Our results indicated that, except for the n-hexane extract, ACM and the various partition extracts at noncytotoxic concentrations effectively decreased melanin content and tyrosinase activity by downregulating microphthalmia-associated transcription factor (MITF) and phosphorylated cAMP response element-binding protein (p-CREB). Moreover, ACM and the partition fractions activated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) to inhibit the synthesis of MITF and finally to decrease melanin production. In conclusion, we suggest that noncytotoxic concentrations of ACM and the various partition fractions may be useful as references for developing skin-lighting agents for use in medicines or cosmetics.

  12. Antioxidant and Cytotoxic Effect of Barringtonia racemosa and Hibiscus sabdariffa Fruit Extracts in MCF-7 Human Breast Cancer Cell Line

    PubMed Central

    Amran, Norliyana; Rani, Anis Najwa Abdul; Mahmud, Roziahanim; Yin, Khoo Boon

    2016-01-01

    Background: The fruits of Barringtonia racemosa and Hibiscus sabdariffa have been used in the treatment of abscess, ulcer, cough, asthma, and diarrhea as traditional remedy. Objective: This study aims to evaluate cytotoxic effect of B. racemosa and H. sabdariffa methanol fruit extracts toward human breast cancer cell lines (MCF-7) and its antioxidant activities. Materials and Methods: Total antioxidant activities of extracts were assayed using 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) and β-carotene bleaching assay. Content of phytochemicals, total flavonoid content (TFC), and total phenolic content (TPC) were determined using aluminum chloride colorimetric method and Folin–Ciocalteu's reagent, respectively. Cytotoxic activity in vitro was investigated through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Results: B. racemosa extract exhibited high antioxidant activities compared to H. sabdariffa methanol fruit extracts in DPPH radical scavenging assay (inhibitory concentration [IC50] 15.26 ± 1.25 μg/mL) and ί-carotene bleaching assay (I% 98.13 ± 1.83%). B. racemosa also showed higher TPC (14.70 ± 1.05 mg gallic acid equivalents [GAE]/g) and TFC (130 ± 1.18 mg quercetin equivalents [QE]/g) compared to H. sabdariffa (3.80 ± 2.13 mg GAE/g and 40.75 ± 1.15 mg QE/g, respectively). In MTT assay, B. racemosa extract also showed a higher cytotoxic activity (IC50 57.61 ± 2.24 μg/mL) compared to H. sabdariffa. Conclusion: The present study indicated that phenolic and flavonoid compounds known for oxidizing activities indicated an important role among the contents of these plants extract. B. racemosa methanol extract have shown potent cytotoxic activity toward MCF-7. Following these promising results, further fractionation of the plant extract is underway to identify important phytochemical bioactives for the development of potential nutraceutical and pharmaceutical use. SUMMARY The phenolic and flavonoid compounds were

  13. Decrease of breast cancer cell invasiveness by sodium phenylacetate (NaPa) is associated with an increased expression of adhesive molecules.

    PubMed

    Vasse, M; Thibout, D; Paysant, J; Legrand, E; Soria, C; Crépin, M

    2001-03-23

    Sodium phenylacetate (NaPa), a non-toxic phenylalanine metabolite, has been shown to induce in vivo and in vitro cytostatic and antiproliferative effects on various cell types. In this work, we analysed the effect of NaPa on the invasiveness of breast cancer cell (MDA-MB-231, MCF-7 and MCF-7 ras). Using the highly invasive breast cancer cell line MDA-MB-231, we demonstrated that an 18-hour incubation with NaPa strongly inhibits the cell invasiveness through Matrigel (86% inhibition at 20 mM of NaPa). As cell invasiveness is greatly influenced by the expression of urokinase (u-PA) and its cell surface receptor (u-PAR) as well as the secretion of matrix metalloproteinases (MMP), we tested the effect of NaPa on these parameters. An 18-hour incubation with NaPa did not modify u-PA expression, either on MDA-MB-231 or on MCF-7 and MCF-7 ras cell lines, and induced a small u-PA decrease after 3 days of treatment of MDA-MB-321 with NaPa. In contrast, an 18 h incubation of MDA-MB-231 increased the expression of u-PAR and the secretion of MMP-9. As u-PAR is a ligand for vitronectin, a composant of the extracellular matrix, these data could explain the increased adhesion of MDA-MB-231 to vitronectin, while cell adhesivity of MCF-7 and MCF-7 ras was unmodified by NaPa treatment. NaPa induced also an increased expression of both Lymphocyte Function-Associated-1 (LFA-1) and Intercellular Adhesion Molecule-1 (ICAM-1), which was obvious from 18 hour incubation with NaPa for the MDA-MB-231 cells, but was delayed (3 days) for MCF-7 and MCF-7 ras. Only neutralizing antibodies against LFA-1 reversed the decreased invasiveness of NaPa-treated cells. Therefore we can conclude that the strong inhibition of MDA-MB-231 invasiveness is not due to a decrease in proteases involved in cell migration (u-PA and MMP) but could be related both to the modification of cell structure and an increased expression of adhesion molecules such as u-PAR and LFA-1.

  14. Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin.

    PubMed

    Kim, Kwang-Youn; Kim, Sang-Hun; Yu, Sun-Nyoung; Park, Suel-Ki; Choi, Hyeun-Deok; Yu, Hak-Sun; Ji, Jae-Hoon; Seo, Young-Kyo; Ahn, Soon-Cheol

    2015-08-01

    Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicin-resistant MCF-7/MDR human breast cancer cells. The results demonstrated that doxorubicin-mediated cytotoxicity was significantly enhanced by salinomycin in the MCF-7/MDR cells, and this occurred in a dose-dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin-treated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR-1 and MRP-1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF-7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapy.

  15. Artemisia iwayomogi Extract Attenuates High-Fat Diet-Induced Obesity by Decreasing the Expression of Genes Associated with Adipogenesis in Mice

    PubMed Central

    Choi, Yeji; Yanagawa, Yasuko; Kim, Sungun; Whang, Wan Kyunn; Park, Taesun

    2013-01-01

    The objective of the present study was to determine whether Artemisia iwayomogi (AI) extract reduces visceral fat accumulation and obesity-related biomarkers in mice fed a high-fat diet (HFD), and if so, whether these effects are exerted by modulation of the expression of genes associated with adipogenesis and inflammation. AI extract supplementation for 11 weeks significantly prevented HFD-induced increments in body weight, visceral adiposity, adipocyte hypertrophy, and plasma levels of lipids and leptin. Additionally, AI extract supplementation resulted in downregulation of adipogenic transcription factors (PPARγ2 and C/EBPα) and their target genes (CD36, aP2, and FAS) in epididymal adipose tissue compared to the HFD alone. The AI extract effectively reversed the HFD-induced elevations in plasma glucose and insulin levels and the homeostasis model assessment of insulin resistance index. Furthermore, the extract significantly decreased gene expression of proinflammatory cytokines (TNFα, MCP1, IL-6, IFNα, and INFβ) in epididymal adipose tissue and reduced plasma levels of TNFα and MCP1 as compared to HFD alone. In conclusion, these results suggest that AI extract may prevent HFD-induced obesity and metabolic disorders, probably by downregulating the expression of genes related to adipogenesis and inflammation in visceral adipose tissue. PMID:23401719

  16. Acceleration of pro-caspase-3 maturation and cell migration inhibition in human breast cancer cells by phytoconstituents of Rheum emodi rhizome extracts

    PubMed Central

    Naveen Kumar, D.R.; George, V. Cijo; Suresh, P.K.; Kumar, R. Ashok

    2013-01-01

    The aggressive nature of estrogen receptor (ER)-negative breast cancer subtype obligates for innovative targeted therapies. The present study aimed to investigate the phytoconstituents and specific anticancer activities of Rheum emodi rhizome, a known food source used locally to treat various ailments. Petroleum ether extracts (hot [PHR] and cold [PCR]) of R. emodi, exhibited significant free radical scavenging potentials through DPPH and reducing power assays, rendering them as good sources of antioxidants. The extracts, PHR and PCR had shown significant (P < 0.05) cancer-cell-specific cytotoxicity in the assayed cells (MDA-MB-231 [breast carcinoma] and WRL-68 [non-tumoral]) at 100 μg/ml, and 50 and 100 μg/ml concentrations respectively. Extracts also induced fervent apoptosis in ER-negative cells (MDA-MB-231) compared to ER-positive subtype (MCF-7), and found to involve CPP32/caspase-3 in its apoptosis induction mechanism. Moreover, extracts had an inevitable potential to inhibit the migration of metastatic breast cancer cells (MDA-MB-231) in vitro. Further, the active principles of extracts were identified through HPLC and GC-MS analysis to reveal major polyphenolics, 4,7-Dimethyl-(octahydro)indolo[4,3-fg]quinolin-10-one, 5-Oxo-isolongifolene, Valencene-2, and other quinone, quinoline and anthraquinone derivatives. The extracts are thus good candidates to target malignant ER-negative breast cancer, and the identified phytoconstituents could be eluted in further exploratory studies for use in dietary-based anti-breast cancer therapies. PMID:26417238

  17. Rhododendron oldhamii leaf extract improves fatty liver syndrome by increasing lipid oxidation and decreasing the lipogenesis pathway in mice

    PubMed Central

    Liu, Ya-Ling; Lin, Lei-Chen; Tung, Yu-Tang; Ho, Shang-Tse; Chen, Yao-Li; Lin, Chi-Chen; Wu, Jyh-Horng

    2017-01-01

    Some members of Rhododendron genus are traditionally used as medicinal plants for arthritis, acute and chronic bronchitis, asthma, pain, inflammation, rheumatism, hypertension and metabolic diseases. To the best of our knowledge, there is no report on the protective effects of R. oldhamii leaf extract on non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. In this study, the effects of R. oldhamii leaf extract on inhibiting the free fatty acid (FFA)-induced accumulation of fat in HepG2 cells and on improving fatty liver syndrome in mice with high fat diet (HFD)-induced NAFLD were investigated. For the in vitro assay, HepG2 cells were treated with FFAs (oleate/palmitate = 2:1) with or without treatment with R. oldhamii leaf ethyl acetate (EtOAc) fraction to observe lipid accumulation using Nile red and oil red O stains. For the in vivo assay, C57BL/6 mice were randomly assigned to three groups (n = 5), including the normal diet group, the HFD group and the HFD+EtOAc group. After 11 weeks, body weight, serum biochemical indices and the mRNA expressions of the liver tissue, as well as the outward appearance, weight and histopathological analysis of liver and adipose tissues were evaluated. Among the fractions derived from R. oldhamii leaf, the EtOAc fraction exhibited a strong fat-accumulation inhibitory activity. Following reverse-phase high-performance liquid chromatography (HPLC), four specific phytochemicals, including (2R, 3R)-astilbin (AS), hyposide (HY), guaijaverin (GU) and quercitrin (QU), were isolated and identified from the EtOAc fraction of R. oldhamii leaf extract. Among them, AS and HY showed excellent fat-accumulation inhibitory activity. Thus, the EtOAc fraction of R. oldhamii leaf and its derived phytochemicals have great potential in preventing FFA-induced fat accumulation. In addition, the EtOAc fraction of R. oldhamii leaf significantly improved fatty liver syndrome and reduced total cholesterol (TC) and triglyceride (TG) in HFD

  18. Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy.

    PubMed

    Liu, Zhongbo; Li, Xuesen; Simoneau, Anne R; Jafari, Mahtab; Zi, Xiaolin

    2012-03-01

    The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti-aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high altitude or cold regions of the world, has been reported to have anti-aging effects in Drosophila. We demonstrated that a R. rosea extract and one of its bioactive components, salidroside, inhibited the growth of bladder cancer cell lines with a minimal effect on nonmalignant bladder epithelial cells TEU-2. Interestingly, the R. rosea extract and salidroside component exhibited a selective ability to inhibit the growth of p53 knockout primary mouse embryo fibroblasts (p53-/- MEFs) compared to their wild-type counterparts. The growth inhibitory effects of the R. rosea extract and salidroside were, however, attenuated in TSC2 and p53 double knock MEFs (TSC2-/-, p53-/- MEFs), suggesting that TSC2 protein is, at least in part, required for the growth inhibitory effects of the R. rosea extract and salidroside. The R. rosea extract and salidroside treatment of UMUC3 cells resulted in an increase of AMP-activated protein kinase (AMPK)-α phosphorylation and a decrease of 4E-BP1 phosphorylation, leading to increased binding of 4E-BP1 to m7 GTP. These results indicate that the R. rosea extract and salidroside inhibit translation initiation. Furthermore, both the R. rosea extract and salidroside treatment of UMUC3 cells caused a significant percentage of cells undergoing autophagy. Therefore, the R. rosea extract and salidroside deserve further study as novel agents for chemoprevention of bladder carcinogenesis. Copyright © 2011 Wiley Periodicals, Inc.

  19. Rhodiola rosea extracts and salidroside decrease the growth of bladder cancer cell lines via inhibition of the mTOR pathway and induction of autophagy

    PubMed Central

    Liu, Zhongbo; Li, Xuesen; Simoneau, Anne R.; Jafari, Mahtab; Zi, Xiaolin

    2011-01-01

    The incidence of human urinary bladder cancer increases markedly with age, suggesting a mechanistic connection between aging and bladder carcinogenesis and a potential use of anti-aging agents in bladder cancer chemoprevention. Rhodiola rosea, growing in high-altitude or cold regions of the world, has been reported to have anti-aging effects in Drosophila. We demonstrated that a R. rosea extract and one of its bioactive components, salidroside, inhibited the growth of bladder cancer cell lines with a minimal effect on non-malignant bladder epithelial cells TEU-2. Interestingly, the R. rosea extract and salidroside component exhibited a selective ability to inhibit the growth of p53 knockout primary mouse embryo fibroblasts (p53−/− MEFs) compared to their wild type counterparts. The growth inhibitory effects of the R. rosea extract and salidroside were, however, attenuated in TSC2 and p53 double knock MEFs (TSC2−/−, p53−/− MEFs), suggesting that TSC2 protein is, at least in part, required for the growth inhibitory effects of the R. rosea extract and salidroside. The R. rosea extract and salidroside treatment of UMUC3 cells resulted in an increase of AMP-activated protein kinase (AMPK)-α phosphorylation and a decrease of 4EBP1 phosphorylation, leading to increased binding of 4EBP1 to m7GTP. These results indicate that the R. rosea extract and salidroside inhibit translation initiation. Furthermore, both the R. rosea extract and salidroside treatment of UMUC3 cells caused a significant percentage of cells undergoing autophagy. Therefore, the R. rosea extract and salidroside deserve further study as novel agents for chemoprevention of bladder carcinogenesis. PMID:21520297

  20. A semianalytic model to extract differential linear scattering coefficients of breast tissue from energy dispersive x-ray diffraction measurements

    SciTech Connect

    LeClair, Robert J.; Boileau, Michel M.; Wang Yinkun

    2006-04-15

    The goal of this work is to develop a technique to measure the x-ray diffraction signals of breast biopsy specimens. A biomedical x-ray diffraction technology capable of measuring such signals may prove to be of diagnostic use to the medical field. Energy dispersive x-ray diffraction measurements coupled with a semianalytical model were used to extract the differential linear scattering coefficients [{mu}{sub s}(x)] of breast tissues on absolute scales. The coefficients describe the probabilities of scatter events occurring per unit length of tissue per unit solid angle of detection. They are a function of the momentum transfer argument, x=sin({theta}/2)/{lambda}, where {theta}=scatter angle and {lambda}=incident wavelength. The technique was validated by using a 3 mm diameter 50 kV polychromatic x-ray beam incident on a 5 mm diameter 5 mm thick sample of water. Water was used because good x-ray diffraction data are available in the literature. The scatter profiles from 6 deg. to 15 deg. in increments of 1 deg. were measured with a 3 mmx3 mmx2 mm thick cadmium zinc telluride detector. A 2 mm diameter Pb aperture was placed on top of the detector. The target to detector distance was 29 cm and the duration of each measurement was 10 min. Ensemble averages of the results compare well with the gold standard data of A. H. Narten [''X-ray diffraction data on liquid water in the temperature range 4 deg. C-200 deg. C, ORNL Report No. 4578 (1970)]. An average 7.68% difference for which most of the discrepancies can be attributed to the background noise at low angles was obtained. The preliminary measurements of breast tissue are also encouraging.

  1. Antiproliferative effect of the Ginkgo biloba extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells.

    PubMed

    Zhao, Xiao-Dan; Dong, Ni; Man, Hong-Tao; Fu, Zhong-Lin; Zhang, Mei-Hong; Kou, Shuang; Ma, Shi-Liang

    2013-09-01

    Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway.

  2. Antiproliferative effect of the Ginkgo biloba extract is associated with the enhancement of cytochrome P450 1B1 expression in estrogen receptor-negative breast cancer cells

    PubMed Central

    ZHAO, XIAO-DAN; DONG, NI; MAN, HONG-TAO; FU, ZHONG-LIN; ZHANG, MEI-HONG; KOU, SHUANG; MA, SHI-LIANG

    2013-01-01

    Ginkgo biloba is a dioecious tree and its extract is a complex mixture that has been used for thousands of years to treat a variety of ailments in traditional Chinese medicine. The aim of this study was to present our observations on the inhibitory effects of different Ginkgo biloba extracts on human breast cancer cell proliferation and growth. Our results demonstrated that treatment of MCF-7 and MDA-MB-231 human breast cancer cells with Ginkgo biloba leaves and ginkgo fruit extract inhibited cell proliferation. It was also observed that this inhibition was accompanied by the enhancement of cytochrome P450 (CYP) 1B1 expression in MDA-MB-231 cells. In addition, treatment with ginkgo fruit extract resulted in a higher CYP1B1 expression in MDA-MB-231 cells compared to treatment with the Ginkgo biloba leaves extract. Our results suggested that the inhibitory effects of the Ginkgo biloba extract on estrogen receptor-negative breast cancer proliferation and the induction of CYP1B1 expression may be exerted through an alternative pathway, independent of the estrogen receptor or the aryl hydrocarbon receptor pathway. PMID:24649031

  3. Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan).

    PubMed

    Abu Bakar, Mohd Fadzelly; Mohamad, Maryati; Rahmat, Asmah; Burr, Steven A; Fry, Jeffrey R

    2010-06-01

    An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5 microg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72 h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36 h for MCF-7 cells and 24 h for MDA-MB-231 cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines.

  4. Validation of self-reported post-treatment mammography surveillance among breast cancer survivors by electronic medical record extraction method.

    PubMed

    Tiro, Jasmin A; Sanders, Joanne M; Shay, L Aubree; Murphy, Caitlin C; A Hamann, Heidi; Bartholomew, L Kay; Savas, Lara S; Vernon, Sally W

    2015-06-01

    Little is known about validity of self-reported mammography surveillance among breast cancer survivors. Most studies have focused on accuracy among healthy, average-risk populations and none have assessed validity by electronic medical record (EMR) extraction method. To assess validity of survivor-reported mammography post-active treatment care, we surveyed all survivors diagnosed 2004-2009 in an academic hospital cancer registry (n = 1441). We used electronic query and manual review to extract EMR data. Concordance, sensitivity, specificity, positive predictive value, and report-to-records ratio were calculated by comparing survivors' self-reports to data from each extraction method. We also assessed average difference in months between mammography dates by source and correlates of concordance. Agreement between the two EMR extraction methods was high (concordance 0.90; kappa 0.70), with electronic query identifying more mammograms. Sensitivity was excellent (0.99) regardless of extraction method; concordance and positive predictive value were good; however, specificity was poor (manual review 0.20, electronic query 0.31). Report-to-records ratios were both over 1 suggesting over-reporting. We observed slight forward telescoping for survivors reporting mammograms 7-12 months prior to survey date. Higher educational attainment and less time since mammogram receipt were associated with greater concordance. Accuracy of survivors' self-reported mammograms was generally high with slight forward telescoping among those recalling their mammograms between 7 and 12 months prior to the survey date. Results are encouraging for clinicians and practitioners relying on survivor reports for surveillance care delivery and as a screening tool for inclusion in interventions promoting adherence to surveillance guidelines.

  5. Validation of self-reported post-treatment mammography surveillance among breast cancer survivors by electronic medical record extraction method

    PubMed Central

    Sanders, Joanne M.; Shay, L. Aubree; Murphy, Caitlin C.; Hamann, Heidi A.; Bartholomew, L. Kay; Savas, Lara S.; Vernon, Sally W.

    2016-01-01

    Little is known about validity of self-reported mammography surveillance among breast cancer survivors. Most studies have focused on accuracy among healthy, average-risk populations and none have assessed validity by electronic medical record (EMR) extraction method. To assess validity of survivor-reported mammography post-active treatment care, we surveyed all survivors diagnosed 2004–2009 in an academic hospital cancer registry (n = 1441). We used electronic query and manual review to extract EMR data. Concordance, sensitivity, specificity, positive predictive value, and report-to-records ratio were calculated by comparing survivors' self-reports to data from each extraction method. We also assessed average difference in months between mammography dates by source and correlates of concordance. Agreement between the two EMR extraction methods was high (concordance 0.90; kappa 0.70), with electronic query identifying more mammograms. Sensitivity was excellent (0.99) regardless of extraction method; concordance and positive predictive value were good; however, specificity was poor (manual review 0.20, electronic query 0.31). Report-to-records ratios were both over 1 suggesting over-reporting. We observed slight forward telescoping for survivors reporting mammograms 7–12 months prior to survey date. Higher educational attainment and less time since mammogram receipt were associated with greater concordance. Accuracy of survivors' self-reported mammograms was generally high with slight forward telescoping among those recalling their mammograms between 7 and 12 months prior to the survey date. Results are encouraging for clinicians and practitioners relying on survivor reports for surveillance care delivery and as a screening tool for inclusion in interventions promoting adherence to surveillance guidelines. PMID:25922083

  6. Effect of selected phytochemicals and apple extracts on NF-kappaB activation in human breast cancer MCF-7 cells.

    PubMed

    Yoon, Hyungeun; Liu, Rui Hai

    2007-04-18

    Nuclear factor kappaB (NF-kappaB) is a transcription factor, which plays an important role in inflammation, cell proliferation, apoptosis, and immunity in eukaryotes. In cancer cells, NF-kappaB induces resistance to anticancer chemotherapeutic agents by increasing cell proliferation and inhibiting apoptosis. Therefore, inhibition of NF-kappaB activation in cancer cells is advantageous in cancer therapy by lowing the resistance to chemotherapy. Several phytochemicals from fruits and vegetables have been reported to inhibit NF-kappaB activation, but the mechanisms of how the phytochemicals work have not been fully understood. The present study examines the effects of selected phytochemicals and apple extracts on TNF-alpha-induced NF-kappaB activation in human breast cancer MCF-7 cells. Apple extracts significantly inhibited the TNF-alpha-induced NF-kappaB activation at a dose of 5 mg/mL (p < 0.05). Curcumin also significantly blocked the TNF-alpha-induced NF-kappaB activation at doses of 10 and 20 microM (p < 0.05). Neither apple extracts nor curcumin affected phosphorylation of inhibitor of NF-kappaB-alpha (IkappaB-alpha); both significantly inhibited proteasomal activity of MCF-7 cells at doses of 2.5 and 5 mg/mL of apple extracts and 20 microM of curcumin (p < 0.05). These results suggest that apple extracts and curcumin have the capabilities of inhibiting TNF-alpha-induced NF-kappaB activation of MCF-7 cells by inhibiting the proteasomal activities instead of IkappaB kinase (IKK) activation.

  7. Ajwa Date (Phoenix dactylifera L.) Extract Inhibits Human Breast Adenocarcinoma (MCF7) Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest.

    PubMed

    Khan, Fazal; Ahmed, Farid; Pushparaj, Peter Natesan; Abuzenadah, Adel; Kumosani, Taha; Barbour, Elie; AlQahtani, Mohammed; Gauthaman, Kalamegam

    2016-01-01

    Phoenix dactylifera L (Date palm) is a native plant of the Kingdom of Saudi Arabia (KSA) and other Middle Eastern countries. Ajwa date has been described in the traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remains to be scientifically validated. Herein, we evaluated the anticancer effects of the Methanolic Extract of Ajwa Date (MEAD) on human breast adenocarcinoma (MCF7) cells in vitro. MCF7 cells were treated with various concentrations (5, 10, 15, 20 and 25 mg/ml) of MEAD for 24, 48 and 72 h and changes in cell morphology, cell cycle, apoptosis related protein and gene expression were studied. Phase contrast microscopy showed various morphological changes such as cell shrinkage, vacuolation, blebbing and fragmentation. MTT (2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay demonstrated statistically significant dose-dependent inhibitions of MCF7 cell proliferation from 35% to 95%. Annexin V-FITC and TUNEL assays showed positive staining for apoptosis of MCF7 cells treated with MEAD (15 mg and 25 mg for 48 h). Flow cytometric analyses of MCF7 cells with MEAD (15 mg/ml and 20 mg/ml) for 24 h demonstrated cell cycle arrest at 'S' phase; increased p53, Bax protein expression; caspase 3activation and decreased the mitochondrial membrane potential (MMP). Quantitative real time PCR (qRT-PCR) analysis showed up-regulation of p53, Bax, Fas, and FasL and down-regulation of Bcl-2. MEAD inhibited MCF7 cells in vitro by the inducing cell cycle arrest and apoptosis. Our results indicate the anticancer effects of Ajwa dates, which therefore may be used as an adjunct therapy with conventional chemotherapeutics to achieve a synergistic effect against breast cancer.

  8. Ajwa Date (Phoenix dactylifera L.) Extract Inhibits Human Breast Adenocarcinoma (MCF7) Cells In Vitro by Inducing Apoptosis and Cell Cycle Arrest

    PubMed Central

    Khan, Fazal; Ahmed, Farid; Pushparaj, Peter Natesan; Abuzenadah, Adel; Kumosani, Taha; Barbour, Elie; AlQahtani, Mohammed; Gauthaman, Kalamegam

    2016-01-01

    Introduction Phoenix dactylifera L (Date palm) is a native plant of the Kingdom of Saudi Arabia (KSA) and other Middle Eastern countries. Ajwa date has been described in the traditional and alternative medicine to provide several health benefits including anticholesteremic, antioxidant, hepatoprotective and anticancer effects, but most remains to be scientifically validated. Herein, we evaluated the anticancer effects of the Methanolic Extract of Ajwa Date (MEAD) on human breast adenocarcinoma (MCF7) cells in vitro. Methods MCF7 cells were treated with various concentrations (5, 10, 15, 20 and 25 mg/ml) of MEAD for 24, 48 and 72 h and changes in cell morphology, cell cycle, apoptosis related protein and gene expression were studied. Results Phase contrast microscopy showed various morphological changes such as cell shrinkage, vacuolation, blebbing and fragmentation. MTT (2-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay demonstrated statistically significant dose-dependent inhibitions of MCF7 cell proliferation from 35% to 95%. Annexin V-FITC and TUNEL assays showed positive staining for apoptosis of MCF7 cells treated with MEAD (15 mg and 25 mg for 48 h). Flow cytometric analyses of MCF7 cells with MEAD (15 mg/ml and 20 mg/ml) for 24 h demonstrated cell cycle arrest at 'S' phase; increased p53, Bax protein expression; caspase 3activation and decreased the mitochondrial membrane potential (MMP). Quantitative real time PCR (qRT-PCR) analysis showed up-regulation of p53, Bax, Fas, and FasL and down-regulation of Bcl-2. Conclusions MEAD inhibited MCF7 cells in vitro by the inducing cell cycle arrest and apoptosis. Our results indicate the anticancer effects of Ajwa dates, which therefore may be used as an adjunct therapy with conventional chemotherapeutics to achieve a synergistic effect against breast cancer. PMID:27441372

  9. Pinus radiata bark extract induces caspase-independent apoptosis-like cell death in MCF-7 human breast cancer cells.

    PubMed

    Venkatesan, Thamizhiniyan; Choi, Young-Woong; Mun, Sung-Phil; Kim, Young-Kyoon

    2016-10-01

    In the present study, we investigated the anticancer activity of Pinus radiata bark extract (PRE) against MCF-7 human breast cancer cells. First, we observed that PRE induces potent cytotoxic effects in MCF-7 cells. The cell death had features of cytoplasmic vacuolation, plasma membrane permeabilization, chromatin condensation, phosphatidylserine externalization, absence of executioner caspase activation, insensitivity to z-VAD-fmk (caspase inhibitor), increased accumulation of autophagic markers, and lysosomal membrane permeabilization (LMP). Both the inhibition of early stage autophagy flux and lysosomal cathepsins did not improve cell viability. The antioxidant, n-acetylcysteine, and the iron chelator, deferoxamine, failed to restore the lysosomal integrity indicating that PRE-induced LMP is independent of oxidative stress. This was corroborated with the absence of enhanced ROS production in PRE-treated cells. Chelation of both intracellular calcium and zinc promotes PRE-induced LMP. Geranylgeranylacetone, an inducer of Hsp70 expression, also had no significant protective effect on PRE-induced LMP. Moreover, we found that PRE induces endoplasmic reticulum (ER) stress and mitochondrial membrane depolarization in MCF-7 cells. The ER stress inhibitor, 4-PBA, did not restore the mitochondrial membrane integrity, whereas cathepsin inhibitors demonstrated significant protective effects. Collectively, our results suggest that PRE induces an autophagic block, LMP, ER stress, and mitochondrial dysfunction in MCF-7 cells. However, further studies are clearly warranted to explore the exact mechanism behind the anticancer activity of PRE in MCF-7 human breast cancer cells.

  10. Curcumin- and natural extract-loaded nanofibres for potential treatment of lung and breast cancer: in vitro efficacy evaluation.

    PubMed

    Sridhar, Radhakrishnan; Ravanan, Swamy; Venugopal, Jayarama Reddy; Sundarrajan, Subramanian; Pliszka, Damian; Sivasubramanian, S; Gunasekaran, P; Prabhakaran, Mohana; Madhaiyan, Kalaipriya; Sahayaraj, Arockia; Lim, Keith Hsiu Chin; Ramakrishna, Seeram

    2014-07-01

    Drug-eluting medical implants are more common, particularly for fighting against cancers. FDA and other drug regulatory bodies have approved many nanoformulated devices eluting active pharmaceutical ingredients and thus there is growing demand for further value- added devices. Nanofibre membranes are known for its versatility of drug incorporation and sustained drug release. We intend to fabricate natural ingredient or extract, and their combination loaded polycaprolactone (PCL) nanofibre for usage as drug-eluting stents or implants for anticancer activity against lung and breast cancers. The fabricated nanofibre membranes were characterised by scanning electron microscope for morphology, FT-IR for chemical nature and tensile testing for mechanical strengths. Release of curcumin was studied with time to find the applicability of the device as drug-eluting implant. The activity of the nanofibre membranes was tested against human breast cancer (MCF7) and lung cancer (A459) cell lines in vitro. In both the cell lines tested, 1% aloe vera and 5% curcumin-loaded PCL nanofibre exhibited 15% more cytotoxicity in comparison with the commercial drug 1% cis-Platin-loaded PCL nanofibre after 24 h incubation.

  11. Decreased expression of B7-H3 reduces the glycolytic capacity and sensitizes breast cancer cells to AKT/mTOR inhibitors

    PubMed Central

    Nunes-Xavier, Caroline E.; Karlsen, Karine Flem; Tekle, Christina; Pedersen, Cathrine; Øyjord, Tove; Hongisto, Vesa; Nesland, Jahn M.; Tan, Ming; Sahlberg, Kristine Kleivi; Fodstad, Øystein

    2016-01-01

    B7 family proteins are important immune response regulators, and can mediate oncogenic signaling and cancer development. We have used human triple-negative breast cancer cell lines with different expression levels of B7-H3 to evaluate its effects on the sensitivity to 22 different anticancer compounds in a drug screen. API-2 (triciribidine) and everolimus (RAD-001), two inhibitors that target the PI3K/AKT/mTOR pathway, showed enhanced inhibition of cell viability and proliferation in B7-H3 knockdown tumor cells compared to their B7-H3 expressing counterparts. Similar inhibition was seen in control cells treated with an anti-B7-H3 monoclonal antibody. In B7-H3 overexpressing cells, the effects of the two drugs were reduced, supported also by in vivo experiments in which B7-H3 overexpressing xenografts were less sensitive to everolimus than control tumors. In API-2 and everolimus-treated B7-H3 overexpressing cells, phospho-mTOR levels were decreased. However, phosphorylation of p70S6K was differentially regulated in B7-H3 cells treated with API-2 or everolimus, suggesting a different B7-H3-mediated mechanism downstream of mTOR. Both API-2 and everolimus decreased the glycolysis of the cells, whereas knockdown of B7-H3 decreased and B7-H3 overexpression increased the glycolytic capacity. In conclusion, we have unveiled a previously unknown relationship between B7-H3 expression and glycolytic capacity in tumor cells, and found that B7-H3 confers resistance to API-2 and everolimus. The results provide novel insights into the function of B7-H3 in cancer, and suggest that targeting of B7-H3 may be a novel alternative to improve current anticancer therapies. PMID:26771843

  12. Use of advanced techniques for the extraction of phenolic compounds from Tunisian olive leaves: phenolic composition and cytotoxicity against human breast cancer cells.

    PubMed

    Taamalli, Amani; Arráez-Román, David; Barrajón-Catalán, Enrique; Ruiz-Torres, Verónica; Pérez-Sánchez, Almudena; Herrero, Miguel; Ibañez, Elena; Micol, Vicente; Zarrouk, Mokhtar; Segura-Carretero, Antonio; Fernández-Gutiérrez, Alberto

    2012-06-01

    A comparison among different advanced extraction techniques such as microwave-assisted extraction (MAE), supercritical fluid extraction (SFE) and pressurized liquid extraction (PLE), together with traditional solid-liquid extraction, was performed to test their efficiency towards the extraction of phenolic compounds from leaves of six Tunisian olive varieties. Extractions were carried out at the best selected conditions for each technique; the obtained extracts were chemically characterized using high-performance liquid chromatography (HPLC) coupled to electrospray time-of-flight mass spectrometry (ESI-TOF-MS) and electrospray ion trap tandem mass spectrometry (ESI-IT-MS(2)). As expected, higher extraction yields were obtained for PLE while phenolic profiles were mainly influenced by the solvent used as optimum in the different extraction methods. A larger number of phenolic compounds, mostly of a polar character, were found in the extracts obtained by using MAE. Best extraction yields do not correlate with highest cytotoxic activity against breast cancer cells, indicating that cytotoxicity is highly dependent on the presence of certain compounds in the extracts, although not exclusively on a single compound. Therefore, a multifactorial behavior is proposed for the anticancer activity of olive leaf compounds.

  13. Green and black tea extracts inhibit HMG-CoA reductase and activate AMP-kinase to decrease cholesterol synthesis in hepatoma cells

    PubMed Central

    Singh, Dev K.; Banerjee, Subhashis; Porter, Todd D.

    2009-01-01

    Recent studies have demonstrated that green and black tea consumption can lower serum cholesterol in animals and in man, and suppression of hepatic cholesterol synthesis is suggested to contribute to this effect. To evaluate this hypothesis, we measured cholesterol synthesis in cultured rat hepatoma cells in the presence of green and black tea extracts and selected components. Green and black tea decreased cholesterol synthesis by up to 55% and 78%, respectively, as measured by a 3-h incorporation of radiolabeled acetate. Inhibition was much less evident when radiolabeled mevalonate was used, suggesting that the inhibition was mediated largely at or above the level of HMG-CoA reductase. Both extracts directly inhibited HMG-CoA reductase when added to microsomal preparations, although the extent of inhibition was considerably less than the decrease in cholesterol synthesis observed in whole cells. As HMG-CoA reductase activity also can be decreased by enzyme phosphorylation by AMP-kinase, the phosphorylation state of HMG-CoA reductase and AMP-kinase, which is activated by phosphorylation, was determined in lysates from cells treated with tea extracts. Both extracts increased AMP-kinase phosphorylation and HMG-CoA reductase phosphorylation by 2.5- to 4-fold, but with different time-courses: maximal phosphorylation with green tea was evident within 30 min of treatment, whereas with black tea phosphorylation was slower to develop, with maximal phosphorylation occurring 3 or more h after treatment. These results suggest that both green and black tea decrease cholesterol synthesis in whole cells by directly inhibiting HMG-CoA reductase and by promoting its inactivation by AMP-kinase. PMID:18926682

  14. Six weeks oral gavage of a Phyllanthus acidus leaf water extract decreased visceral fat, the serum lipid profile and liver lipid accumulation in middle-aged male rats.

    PubMed

    Chongsa, Watchara; Radenahmad, Nisaudah; Jansakul, Chaweewan

    2014-08-08

    Advancing age is associated with an increased accumulation of visceral fat and liver lipid which is then responsible for an age-related risk for cardiovascular disease. Looking after ourselves well with suitable micronutrients could prevent disease or prolong our healthy cardiovascular functions. In Thai traditional medicine, leaves of Phyllanthus acidus (PA) have been used for many purposes including as an antihypertensive agent and to provide relief from a headache caused by hypertension. We aimed to investigate the effects of a chronic oral administration of PA extracts to middle-aged (12-14 months) rats on their body weight, food intake, body fats, liver and kidney functions, fasting blood glucose and lipid profiles, liver lipid accumulation and on blood pressure. Three different kinds of PA extracts were used: (1) a PA water extract, (2) a heated PA water extract, and (3) an n-butanol fraction of the PA water extract, prepared from fresh leaves of Phyllanthus acidus. The rats were orally gavaged with the three PA extracts at 1.0 g/kg body weight or, as a control, with distilled water once a day for 6 weeks. Fasting blood sugar, lipid profile and ALP, SGOT, SGPT, BUN and creatinine levels were measured by enzymatic methods. Liver lipid accumulation was measured using oil red O staining on fresh thin cryostat liver tissue sections. The animal basal blood pressure and heart rate were measured in anesthetized rats via a common carotid artery using a polygraph. Results showed that after 6 weeks of treatment using gavaged heated PA extract and PA n-butanol extract there were no changes in any of the parameters studied. However, the initial PA water extract caused a slight decrease in the animal body weight with no change in food intake. No changes were observed in the liver and kidney functions (serum ALP, SGOT, SGPT, BUN and creatinine did not change), nor did the fasting blood sugar or triglyceride levels differ significantly. Serum cholesterol, HDL and LDL levels

  15. Reproducibility of quantitative high-throughput BI-RADS features extracted from ultrasound images of breast cancer.

    PubMed

    Hu, Yuzhou; Qiao, Mengyun; Guo, Yi; Wang, Yuanyuan; Yu, Jinhua; Li, Jiawei; Chang, Cai

    2017-07-01

    Digital Breast Imaging Reporting and Data System (BI-RADS) features extracted from ultrasound images are essential in computer-aided diagnosis, prediction, and prognosis of breast cancer. This study focuses on the reproducibility of quantitative high-throughput BI-RADS features in the presence of variations due to different segmentation results, various ultrasound machine models, and multiple ultrasound machine settings. Dataset 1 consists of 399 patients with invasive breast cancer and is used as the training set to measure the reproducibility of features, while dataset 2 consists of 138 other patients and is a validation set used to evaluate the diagnosis performances of the final reproducible features. Four hundred and sixty high-throughput BI-RADS features are designed and quantized according to BI-RADS lexicon. Concordance Correlation Coefficient (CCC) and Deviation (Dev) are used to assess the effect of the segmentation methods and Between-class Distance (BD) is used to study the influences of the machine models. In addition, the features jointly shared by two methodologies are further investigated on their effects with multiple machine settings. Subsequently, the absolute value of Pearson Correlation Coefficient (Rabs ) is applied for redundancy elimination. Finally, the features that are reproducible and not redundant are preserved as the stable feature set. A 10-fold Support Vector Machine (SVM) classifier is employed to verify the diagnostic ability. One hundred and fifty-three features were found to have high reproducibility (CCC > 0.9 & Dev < 0.1) within the manual and automatic segmentation. Three hundred and thirty-nine features were stable (BD < 0.2) at different machine models. Two feature sets shared the same 102 features, in which nine features were highly sensitive to the machine settings. Forty-six features were finally preserved after redundancy elimination. For the validation in dataset 2, the area under curve (AUC) of the 10-fold SVM

  16. Dillenia suffruticosa dichloromethane root extract induced apoptosis towards MDA-MB-231 triple-negative breast cancer cells.

    PubMed

    Foo, Jhi Biau; Saiful Yazan, Latifah; Tor, Yin Sim; Wibowo, Agustono; Ismail, Norsharina; Armania, Nurdin; Cheah, Yoke Kqueen; Abdullah, Rasedee

    2016-07-01

    Dillenia suffruticosa is traditionally used for treatment of cancerous growth including breast cancer in Malaysia. Dillenia suffruticosa is a well-known medicinal plant in Malaysia for the treatment of cancer. Nevertheless, no study has been reported the cytotoxicity of this plant towards MDA-MB-231 triple-negative breast cancer cells. The present study was designed to investigate the mode of cell death and signalling pathways of MDA-MB-231 cells treated with dichloromethane Dillenia suffruticosa root extract (DCM-DS). Extraction of Dillenia suffruticosa root was performed by the use of sequential solvent procedure. The cytotoxicity of DCM-DS was determined by using MTT assay. The mode of cell death was evaluated by using an inverted light microscope and flow cytometry analysis using Annexin-V/PI. Cell cycle analysis and measurement of reactive oxygen species level were performed by using flow cytometry. The cells were treated with DCM-DS and antioxidants α-tocopherol or ascorbic acid to evaluate the involvement of ROS in the cytotoxicity of DCM-DS. Effect of DCM-DS on the expression of antioxidant, apoptotic, growth, survival genes and proteins were analysed by using GeXP-based multiplex system and Western blot, respectively. The cytotoxicity of compounds isolated from DCM-DS was evaluated towards MDA-MB-231 cells using MTT assay. DCM-DS induced apoptosis, G2/M phase cell cycle arrest and oxidative stress in MDA-MB-231 cells. The induction of apoptosis in MDA-MB-231 cells by DCM-DS is possibly due to the activation of pro-apoptotic JNK1 and down-regulation of anti-apoptotic ERK1, which in turn down-regulates anti-apoptotic BCL-2 to increase the BAX/BCL-2 ratio to initiate the mitochondrial apoptotic pathway. The cell cycle arrest in DCM-DS-treated MDA-MB-231 cells is possibly via p53-independent but p21-dependent pathway. A total of 3 triterpene compounds were isolated from DCM-DS. Betulinic acid appears to be the most major and most cytotoxic compound in DCM

  17. Extraction and preconcentration of hemin from human blood serum and breast cancer supernatant.

    PubMed

    Sedaghat, Somayeh; Shamspur, Tayebeh; Mohamadi, Maryam; Mostafavi, Ali

    2015-12-01

    A green, facile, fast, and sensitive liquid-phase microextraction method is presented for the extraction and preconcentration of hemin in the presence of free iron ions prior to flame atomic absorption spectroscopic determination. In this technique, an anion-functionalized task-specific ionic liquid is used as the extracting solvent. The interface between the extracting solvent and the bulk aqueous phase containing hemin is enormously enlarged by dispersing the ionic liquid to the aqueous phase with the help of ultrasound radiation. Hemin is selectively extracted into the ionic liquid after interaction with the functional group of the ionic liquid. Then, the concentration of the extracted hemin is determined through the absorbance of the iron ions contained in the hemin structure using flame atomic absorption spectroscopy. Different experimental parameters affecting the extraction efficiency have been optimized. Under the optimized conditions, the proposed method has a hemin concentration linear range of 0.020-0.80 mg/L with a detection limit of 0.0080 mg/L. This method has been successfully applied to the extraction and determination of hemin in human serum and supernatant samples.

  18. Changes in plasma thiol levels induced by different phases of treatment in breast cancer; the role of commercial extract from black chokeberry.

    PubMed

    Kędzierska, Magdalena; Głowacki, Rafał; Czernek, Urszula; Szydłowska-Pazera, Katarzyna; Potemski, Piotr; Piekarski, Janusz; Jeziorski, Arkadiusz; Olas, Beata

    2013-01-01

    Different low-molecular-weight thiols, including glutathione, cysteine, and cysteinylglycine are physiological free radical scavengers. On the other hand, homocysteine may play a role as an oxidant. The aim of our present study was to establish in vitro the effects of the commercial extract of Aronia melanocarpa (Aronox(®)) on the amount of selected low-molecular-weight thiols and the activity of antioxidative enzymes (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in plasma obtained from patients with invasive breast cancer during different phases of treatment [before or after the surgery and patients after different phases of chemotherapy (doxorubicin and cyclophosphamide)] and from healthy subjects. Patients were hospitalized in Department of Oncological Surgery and Department of Chemotherapy, Medical University of Lodz, Poland. The level of low-molecular-weight thiols was determined by high-performance liquid chromatography. We observed that in the presence of the Aronia extract changes in amount of thiols in plasma from breast cancer patients (at all tested groups) were significantly reduced. Our results showed that tested commercial extract reduced modifications of antioxidative enzymes activity in plasma from patients during different phases of treatment, but this effect was not statistical significant. Our results suggest that the Aronia extract supplementation in breast cancer patients has a beneficial effect on thiols concentration in plasma. Plasma, as reported in this work, could be used as an experimental model to evaluate the beneficial action of plant supplements, including phenolic extracts on thiols or other molecules during different phases of treatment.

  19. Syzygium cumini extract decrease adenosine deaminase, 5'nucleotidase activities and oxidative damage in platelets of diabetic patients.

    PubMed

    De Bona, Karine S; Bellé, Luziane P; Sari, Marcel H; Thomé, Gustavo; Schetinger, Maria R C; Morsch, Vera M; Boligon, Aline; Athayde, Margareth L; Pigatto, Aline S; Moretto, Maria B

    2010-01-01

    Diabetes mellitus, a chronic metabolic disorder, has assumed epidemic proportions and its long-term complications can have devastating consequences. The oxidative stress in diabetes was greatly increased due to prolonged exposure to hyperglycemia and impairment of oxidant/antioxidant equilibrium. Syzygium cumini is being widely used to treat diabetes by the traditional practitioners over many centuries. Adenosine deaminase (ADA) and 5'-Nucleotidase (5'NT) are enzymes of purine nucleoside metabolism that play an important role in the regulation of adenosine (Ado) levels. In this study, we investigated the effect of Syzygium cumini aqueous leaves extract (ASc) on ADA and 5'NT activities and on parameters of oxidative stress under in vitro conditions, using platelets of patients with Type 2 diabetes mellitus. Platelet-Rich Plasma (PRP) was assayed by ADA, 5'NT, Catalase (CAT), Superoxide Dismutase (SOD) activities and Thiobarbituric acid reactive substances (TBARS) levels. We observed that ADA, 5'NT activities and TBARS levels were significantly higher when compared to the control group, and ASc (100 and 200 μg/mL) prevented these effects. Our study demonstrates that ASc was able to remove oxidant species generated in diabetic conditions and modulates in the Ado levels. Then, ASc may promote a compensatory response in platelet function, improving the susceptibility-induced by the diabetes mellitus. Copyright © 2010 S. Karger AG, Basel.

  20. Agrimonia pilosa Ledeb. aqueous extract improves impaired glucose tolerance in high-fat diet-fed rats by decreasing the inflammatory response.

    PubMed

    Jang, Hwan Hee; Nam, Song Yee; Kim, Mi Ju; Kim, Jung Bong; Choi, Jeong Sook; Kim, Haeng Ran; Lee, Young Min

    2017-09-05

    Agrimonia pilosa Ledeb. is a medicinal plant with physiological activities such as anti-cancer, antioxidant, anti-inflammatory activities and in vitro anti-diabetic activity. However, the effects of aqueous extracts from A. pilosa on insulin-resistant rats have not yet been examined. We investigated the effects of aqueous extract from A. pilosa on impaired glucose metabolism induced by a high-fat diet in rats. Male Sprague-Dawley rats were assigned to the following groups: normal-fat diet (NF, n = 9); high-fat diet (HF, n = 9); high-fat diet with 0.1% A. pilosa aqueous extract (HFA, n = 10). Experimental diets were administered for 16 weeks. At the end of the treatment, liver and fat tissues were isolated, and serum was collected for biochemical analysis. The HF group rats had a significantly higher liver weight than the NF group rats did, and increased hepatic lipid accumulation (p < 0.05); however, supplementation with A. pilosa decreased liver weight. Blood glucose levels in the HFA group were lower than levels measured in the HF group 30, 60, and 120 min after glucose administration (p < 0.05). In addition, dietary A. pilosa supplementation decreased tumor necrosis factor α and interleukin 6 levels, while increasing serum adiponectin concentrations (p < 0.05 vs. the HF group). These effects were accompanied by reduced hepatic and adipose tissue expression of inflammation-related genes such as Tnf and Il1b (p < 0.05). Our findings indicate that A. pilosa aqueous extract can ameliorate insulin resistance in high-fat diet-fed rats by decreasing the inflammatory response.

  1. Characterization of Bizzy Nut extracts in estrogen-responsive MCF-7 breast cancer cells

    SciTech Connect

    Fontenot, Krystal . E-mail: Krystal_Fontenot_01@subr.edu; Naragoni, Srivatcha . E-mail: Srivatcha_Naragoni00@subr.edu; Claville, Michelle . E-mail: Michelle_Claville@subr.edu; Gray, Wesley . E-mail: wesley_gray@subr.edu

    2007-04-01

    Kola acuminate, also known as Bizzy Nut or Kola Nut, is a natural product that contains bioactive chemicals that possess hormonal properties. The purpose of this study was to characterize the putative phytoestrogenic compounds present in Bizzy Nut for estrogenic-like activity. As an initial step, five extracts (E1 - hexane, E2 - ether, E3 - acetone, E4 - methanol and E5 - water) were sequentially generated using solid-liquid phase extraction and their bioactivity was examined in MCF-7, MDA-MB-468 and LNCaP cancer cell models. MTT cell viability, dye exclusion, caspase activity and microscopic assessment of apoptotic cells demonstrated that extracts of Bizzy were cytotoxic to MCF-7, MDA-MB 468 and LNCaP cells. In MCF-7 cells, the acetone extract (E3) at 100 ppm elicited a potent cytotoxic response with a growth-inhibitory concentration (GI{sub 50}) of 67 ppm. In contrast, E3 stimulated growth in LNCaP cells. The ether extract (E2) showed a dose-dependent cytotoxic response with a GI{sub 50} of 13 ppm in the LNCaP cell line. Examination of the apoptotic response induced by E2 and E3 paralleled the level of cell cytotoxicity observed in both cell lines. The methanol extract (E4) was the only extract that showed a time-, dose-, and estrogen-receptor-dependent stimulation of pS2 gene expression. On the other hand, the acetone extract (E3), which showed the highest degree of cytotoxicity, showed no transcription stimulation of pS2 in MCF-7 cells. Altogether, these data indicate that Bizzy contains unique active hormonal compounds that have specific biological properties that are cell line-dependent.

  2. Cytotoxic activity of methanolic extract of Mentha longifolia and Ocimum basilicum against human breast cancer.

    PubMed

    Al-Ali, Khalil H; El-Beshbishy, Hesham A; El-Badry, Ayman A; Alkhalaf, Moussa

    2013-12-01

    Labiatae family is represented in Saudi Arabia. The aim of the present study was to go insight to investigate the anticancer activity and antioxidative potentials of methanolic extracts of Mentha longifolia L. (ML) and Ocimum basilicum L. (OB) that grown in Madina province, western region, Saudi Arabia. OB exhibited the greater phenolic contents as mg gallic acid equivalent/g weight (mg GAE/g) for a value of 105 +/- 5.5 mg GAE/g. On the other hand, ML produced 29 +/- 3.12 mg GAE/g. The standard antioxidant vitamin E used in this experiment elicited a value of total phenolic contents equal 22 +/- 2.2 mg GAE/g. The percentage scavenging activity of against diphenylpicrylhydrazyl (DPPH) was 850 and 160% for OB and ML extracts, respectively. Vitamin E elicited% scavenging activity of against DPPH equal to 198%. Brine shrimp cytotoxic assay clearly indicated the cytotoxic effects of either ML or OB extract. The brine shrimp survival is inversely proportional to the concentration of either ML or OB extract used with LD50 191.23 and 235.50 ppm, respectively. Toxic effects on brine shrimps indicated the anticancer potential of ML or OB extract. The ML or OB extract was unable to produce pbluescript (pBS) plasmid DNA damage, while the plasmid DNA treated with EcoRI produced a single band as a result of DNA damage. Also, both ML and OB extract exhibited marked cytotoxic activity against MCF-7 cells at various concentrations (20, 40, 80, 160 and 320 microg mL(-1)). The 160 and 320 microg mL(-1) showed more cytotoxic effect against MCF-7 cells. Based on results achieved, we can concluded that, OB and ML extracts have the potency to act as powerful antioxidants and protect against DNA damage and have cytotoxic activity against MCF-7 cell line.

  3. Effects of Mung Bean (Vigna radiata L.) Ethanol Extracts Decrease Proinflammatory Cytokine-Induced Lipogenesis in the KK-Ay Diabese Mouse Model.

    PubMed

    Kang, Inhae; Choi, Seojin; Ha, Tae Joung; Choi, Munji; Wi, Hae-Ri; Lee, Byong Won; Lee, Myoungsook

    2015-08-01

    Rapid increase in the prevalence of obesity-related metabolic inflammatory diseases has led to research focused on nutraceuticals for their treatment. This study investigated the effects of the ethanol extracts of mung bean testa (MBT) on the metabolic inflammation-induced lipogenesis in gastrocnemius muscle of KK-Ay diabese mice. Ethanol extracts of MBT were orally administered to diabese KK-Ay mice for 4 weeks after diet-induced obesity model was generated by feeding a 60% high-fat diet for 3 weeks. Although there were no changes in body weight gain, MBT treatments decreased total weight of white adipose tissue. MBT also decreased triacylglycerol and total cholesterol levels in the muscle by 30%, which was correlated with suppression of lipogenic genes such as ACC, C/EBP alpha, PGC-1 alpha, and PPAR gamma. In particular, decreased levels of p-ERK1/2, PPAR gamma, and C/EBP alpha in the MBT-treated groups suggest that MBT might inhibit adipogenesis and decrease differentiation via the MEK/ERK pathway. Furthermore, significantly lower amounts of plasma interleukin (IL)-6 and intramuscular tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein-1 (MCP-1) were detected in MBT groups, confirming the anti-inflammatory effect of mung bean. In addition, our in vitro pilot study with 3T3-L1 cells showed that vitexin, the functional chemical in MBT, inhibited inflammation-induced lipogenesis with significantly lower amounts of IL-6 and MCP-1 after 14 days of vitexin treatment. Thus, the functional compounds in the mung bean ethanol extracts such as vitexin and isovitexin may regulate intracellular lipogenesis and adipogenesis via anti-inflammatory mechanisms and MEK/ERK pathway in the KK-Ay mouse model.

  4. Effects of Mung Bean (Vigna radiata L.) Ethanol Extracts Decrease Proinflammatory Cytokine-Induced Lipogenesis in the KK-Ay Diabese Mouse Model

    PubMed Central

    Kang, Inhae; Choi, Seojin; Ha, Tae Joung; Choi, Munji; Wi, Hae-Ri; Lee, Byong Won

    2015-01-01

    Abstract Rapid increase in the prevalence of obesity-related metabolic inflammatory diseases has led to research focused on nutraceuticals for their treatment. This study investigated the effects of the ethanol extracts of mung bean testa (MBT) on the metabolic inflammation-induced lipogenesis in gastrocnemius muscle of KK-Ay diabese mice. Ethanol extracts of MBT were orally administered to diabese KK-Ay mice for 4 weeks after diet-induced obesity model was generated by feeding a 60% high-fat diet for 3 weeks. Although there were no changes in body weight gain, MBT treatments decreased total weight of white adipose tissue. MBT also decreased triacylglycerol and total cholesterol levels in the muscle by 30%, which was correlated with suppression of lipogenic genes such as ACC, C/EBP alpha, PGC-1 alpha, and PPAR gamma. In particular, decreased levels of p-ERK1/2, PPAR gamma, and C/EBP alpha in the MBT-treated groups suggest that MBT might inhibit adipogenesis and decrease differentiation via the MEK/ERK pathway. Furthermore, significantly lower amounts of plasma interleukin (IL)-6 and intramuscular tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein-1 (MCP-1) were detected in MBT groups, confirming the anti-inflammatory effect of mung bean. In addition, our in vitro pilot study with 3T3-L1 cells showed that vitexin, the functional chemical in MBT, inhibited inflammation-induced lipogenesis with significantly lower amounts of IL-6 and MCP-1 after 14 days of vitexin treatment. Thus, the functional compounds in the mung bean ethanol extracts such as vitexin and isovitexin may regulate intracellular lipogenesis and adipogenesis via anti-inflammatory mechanisms and MEK/ERK pathway in the KK-Ay mouse model. PMID:25826234

  5. Heartwood extract of Acacia catechu induces apoptosis in human breast carcinoma by altering bax/bcl-2 ratio

    PubMed Central

    Ghate, Nikhil Baban; Hazra, Bibhabasu; Sarkar, Rhitajit; Mandal, Nripendranath

    2014-01-01

    Background: The heartwood extract of A. catechu, called pale catechu or “Katha” in Hindi has been widely used in traditional Indian medicinal system. Although various pharmacological properties of this plant had been reported previously, only a few were concerned with the anticancer activity of this plant. Objective: The objective was to assess the in vitro anticancer and apoptosis inducing effect of 70% methanolic extract of “Katha” (ACME) on human breast adenocarcinoma cell line (MCF-7). Materials and Methods: MCF-7 cell line was treated with increasing concentrations of ACME and cell viability was calculated. Flow cytometric methods were used to confirm the apoptosis promoting role of ACME. Morphological changes were then analysed using confocal microscopy. Western blotting was then performed to investigate the expression of apoptogenic proteins and to analyse the activation of caspases. Results: ACME showed significant cytotoxicity to MCF-7 cells with an IC50 value of 288.85 ± 25.79 μg/ml. Flow cytometric analysis and morphological studies confirmed that ACME is able to induce apoptosis in MCF-7 cells. Furthermore, immunoblot results suggested the pathway of apoptosis induction by increasing Bax/Bcl-2 ratio which results in the activation of caspase-cascade and ultimately leads to the cleavage of Poly adeno ribose polymerase (PARP). Conclusion: These results provide the evidence that ACME is able to inhibit the proliferation of MCF-7 cells by inducing apoptosis through intrinsic pathway. PMID:24695415

  6. Biotransformed soybean extract induces cell death of estrogen-dependent breast cancer cells by modulation of apoptotic proteins.

    PubMed

    Stocco, Bianca; Toledo, Karina A; Fumagalli, Helen F; Bianchini, Francine J; Fortes, Vanessa S; Fonseca, Maria José V; Toloi, Maria Regina T

    2015-01-01

    The process of soybean biotransformation increases the quantity of isoflavones (daidzein and genistein), which besides being considered an alternative to estroprogestive hormone replacement therapy (HRT), are able of hindering the growth and development of tumor cells. We investigated the effects of soybean extract biotransformed by fungus on estrogen-dependent (MCF-7) and nondependent (SK-BR-3) breast cell lines. Cells were treated with different concentrations of biotransformed (BSE) and nonbiotransformed soybean extract (SE), or daidzein (D) and genistein (G) patterns isolated and in combination (D + G). Afterwards, we analyzed cell viability by MTT assay, phosphatidylserine exposure and cell permeability by flow cytometry; expression of apoptotic proteins by Western blotting. BSE promoted reduction in cell viability and increase in DNA degradation in both cell lines. In addition, we verified increase in cell permeability and in the expression of phosphatidylserine, as well as modulation in the expression of apoptotic proteins in MCF-7 cells. The cells did not show any signs of cell death when incubated with the controls (D, G, and D + G). Unknown components found in the BSE induce cell death by apoptosis and necrosis, mainly in MCF-7 cells. These processes depend on the activation of caspase-3 and involve an increase in the expression of proapoptotic molecules.

  7. Medications to decrease the risk for breast cancer in women: recommendations from the U.S. Preventive Services Task Force recommendation statement.

    PubMed

    Moyer, Virginia A

    2013-11-19

    Update of the 2002 U.S. Preventive Services Task Force (USPSTF) recommendation on the use of medications for breast cancer risk reduction. The USPSTF reviewed evidence on the effectiveness,adverse effects, and subgroup variations of medications to reduce the risk for breast cancer—specifically, the selective estrogen receptor modulators tamoxifen and raloxifene. The USPSTF also reviewed a meta-analysis of placebo-controlled trials to understand the relative benefits and harms of tamoxifen and raloxifene. This recommendation applies to asymptomatic women aged 35 years or older without a prior diagnosis of breast cancer,ductal carcinoma in situ, or lobular carcinoma in situ. The USPSTF recommends that clinicians engage in shared, informed decision making with women who are at increased risk for breast cancer about medications to reduce their risk.For women who are at increased risk for breast cancer and at low risk for adverse medication effects, clinicians should offer to prescribe risk-reducing medications, such as tamoxifen or raloxifene. (B recommendation)The USPSTF recommends against the routine use of medications,such as tamoxifen or raloxifene, for risk reduction of primary breast cancer in women who are not at increased risk for breast cancer. (D recommendation).

  8. Flavonoid C-glucosides Derived from Flax Straw Extracts Reduce Human Breast Cancer Cell Growth In vitro and Induce Apoptosis

    PubMed Central

    Czemplik, Magdalena; Mierziak, Justyna; Szopa, Jan; Kulma, Anna

    2016-01-01

    Flax straw of flax varieties that are grown for oil production is a by product which represents a considerable biomass source. Therefore, its potential application for human use is of high interest. Our research has revealed that flax straw is rich in flavonoid C-glucosides, including vitexin, orientin, and isoorientin. The objective of this study was to evaluate the cytotoxicity and possible proapoptotic effect of flax straw derived C-glucosides of flavonoids in the human breast adenocarcinoma cell line (MCF-7). The effects of flax straw derived flavonoid C-glucosides on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B assays. The expression of apoptosis-related genes was assessed by real-time PCR. Our data revealed that flax C-glucosides as well as pure compounds are cytotoxic toward MCF-7 cells and inhibit their proliferation. Moreover, the induction of apoptosis was correlated with the changes in the mRNA level of pro-apoptotic genes. Increased expression of bax and caspase-7, -8, and -9 and decreased mRNA expression of bcl-2 was observed, whereas the mRNA levels of p53 and mdm2 were not altered. These results clearly demonstrated that flax straw metabolites effectively induced growth inhibition and apoptosis in human breast adenocarcinoma cells. PMID:27630565

  9. Flavonoid C-glucosides Derived from Flax Straw Extracts Reduce Human Breast Cancer Cell Growth In vitro and Induce Apoptosis.

    PubMed

    Czemplik, Magdalena; Mierziak, Justyna; Szopa, Jan; Kulma, Anna

    2016-01-01

    Flax straw of flax varieties that are grown for oil production is a by product which represents a considerable biomass source. Therefore, its potential application for human use is of high interest. Our research has revealed that flax straw is rich in flavonoid C-glucosides, including vitexin, orientin, and isoorientin. The objective of this study was to evaluate the cytotoxicity and possible proapoptotic effect of flax straw derived C-glucosides of flavonoids in the human breast adenocarcinoma cell line (MCF-7). The effects of flax straw derived flavonoid C-glucosides on cell proliferation of MCF-7 cells were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and sulforhodamine B assays. The expression of apoptosis-related genes was assessed by real-time PCR. Our data revealed that flax C-glucosides as well as pure compounds are cytotoxic toward MCF-7 cells and inhibit their proliferation. Moreover, the induction of apoptosis was correlated with the changes in the mRNA level of pro-apoptotic genes. Increased expression of bax and caspase-7, -8, and -9 and decreased mRNA expression of bcl-2 was observed, whereas the mRNA levels of p53 and mdm2 were not altered. These results clearly demonstrated that flax straw metabolites effectively induced growth inhibition and apoptosis in human breast adenocarcinoma cells.

  10. Daily ingestion of grains of paradise (Aframomum melegueta) extract increases whole-body energy expenditure and decreases visceral fat in humans.

    PubMed

    Sugita, Jun; Yoneshiro, Takeshi; Sugishima, Yuuki; Ikemoto, Takeshi; Uchiwa, Hideyo; Suzuki, Isao; Saito, Masayuki

    2014-01-01

    We reported previously that a single ingestion of an alcohol extract of grains of paradise (GP, Aframomum melegueta), a species of the ginger family, increases energy expenditure (EE) through the activation of brown adipose tissue, a site of sympathetically mediated metabolic theromogenesis. The present study aimed to examine a daily ingestion of GP extract on whole-body EE and body fat in humans. Whole-body EE and body fat content were measured before and after daily oral ingestion of GP extract (30 mg/d) for 4 wk in 19 non-obese female volunteers aged 20-22 y in a single-blind, randomized, placebo-controlled, crossover design. Four-week daily ingestion of GP and a placebo decreased and increased slightly the visceral fat area at the umbilicus level, respectively. The GP-induced change was significantly different from that induced by the placebo (p<0.05), and negatively correlated with the initial visceral fat area (r=-0.64, p<0.01). Neither GP nor placebo ingestion affected subcutaneous or total fat. The daily ingestion of GP, but not the placebo, increased whole-body EE (p<0.05). These results suggest that GP extract may be an effective and safe tool for reducing body fat, mainly by preventing visceral fat accumulation.

  11. Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer's disease.

    PubMed

    Hritcu, Lucian; Noumedem, Jaurès A; Cioanca, Oana; Hancianu, Monica; Kuete, Victor; Mihasan, Marius

    2014-04-01

    The present study analyzed the possible memory-enhancing and antioxidant proprieties of the methanolic extract of Piper nigrum L. fruits (50 and 100 mg/kg, orally, for 21 days) in amyloid beta(1-42) rat model of Alzheimer's disease. The memory-enhancing effects of the plant extract were studied by means of in vivo (Y-maze and radial arm-maze tasks) approaches. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase-, catalase-, glutathione peroxidase-specific activities and the total content of reduced glutathione, malondialdehyde, and protein carbonyl levels. The amyloid beta(1-42)-treated rats exhibited the following: decrease of spontaneous alternations percentage within Y-maze task and increase of working memory and reference memory errors within radial arm-maze task. Administration of the plant extract significantly improved memory performance and exhibited antioxidant potential. Our results suggest that the plant extract ameliorates amyloid beta(1-42)-induced spatial memory impairment by attenuation of the oxidative stress in the rat hippocampus.

  12. Green tea extract decreases starch digestion and absorption from a test meal in humans: a randomized, placebo-controlled crossover study.

    PubMed

    Lochocka, Klaudia; Bajerska, Joanna; Glapa, Aleksandra; Fidler-Witon, Ewa; Nowak, Jan K; Szczapa, Tomasz; Grebowiec, Philip; Lisowska, Aleksandra; Walkowiak, Jaroslaw

    2015-07-30

    Green tea is known worldwide for its beneficial effects on human health. However, objective data evaluating this influence in humans is scarce. The aim of the study was to assess the impact of green tea extract (GTE) on starch digestion and absorption. The study comprised of 28 healthy volunteers, aged 19 to 28 years. In all subjects, a starch (13)C breath test was performed twice. Subjects randomly ingested naturally (13)C-abundant cornflakes during the GTE test (GTE 4 g) or placebo test. The cumulative percentage dose recovery (CPDR) was significantly lower for the GTE test than for the placebo test (median [interquartile range]: 11.4% [5.5-15.5] vs. 16.1% [12.7-19.5]; p = 0.003). Likewise, CPDR expressed per hour was considerably lower in each point of the measurement. In conclusion, a single dose of green tea extract taken with a test meal decreases starch digestion and absorption.

  13. Clinical and immunological assessment in breast cancer patients receiving anticancer therapy and bovine dialyzable leukocyte extract as an adjuvant.

    PubMed

    Lara, Humberto H; Turrent, Liliana Ixtepan; Garza-Treviño, Elsa N; Tamez-Guerra, Reyes; Rodriguez-Padilla, Cristina

    2010-05-01

    Dialyzable leukocyte extract (DLE) is one of the immunological agents used as an adjuvant in cancer therapy; it has been associated with improved quality of life during cancer chemotherapy. Based on these previous findings and on the observed clinical benefits attributed to DLE in other types of cancer, we investigated its clinical and immunological effects as a therapy adjuvant on breast cancer patients who received only chemotherapy, as compared to patients administered bovine DLE (bDLE) as an adjuvant. This study included 43 breast cancer patients who were about to begin chemotherapy. This group was divided as follows: 25 received chemotherapy and bDLE as an adjuvant therapy, and 18 received only chemotherapy without the adjuvant. All patient clinical and immunological responses were monitored. Among patients in the group that received bDLE as adjuvant, 60% showed a complete response, 32% showed a partial response and 8% did not respond. By contrast, in the group without the adjuvant, 39% showed a complete response, 50% displayed a partial response and 11% were non-responders. In addition, bDLE treatment in combination with chemotherapy resulted in the enhancement of the Karnofsky performance scale during chemotherapy. Even though patients underwent several cycles of chemotherapy without bDLE, the lymphocyte population dropped to below the reference value. On the other hand, in patients with bDLE as adjuvant, the CD4(+) and CD8(+) lymphocytes and the B lymphocytes were maintained within the median range of the reference value. The number of natural killer cells also increased after chemotherapy treatment with bDLE as an adjuvant. In conclusion, bDLE treatment contributes to significant immunological recovery in patients that have undergone heavy chemotherapy, increasing the clinical response and quality of life during chemotherapy.

  14. Radish (Raphanus sativus L. leaf) ethanol extract inhibits protein and mRNA expression of ErbB(2) and ErbB(3) in MDA-MB-231 human breast cancer cells.

    PubMed

    Kim, Woo Kyoung; Kim, Ji Hae; Jeong, Da Hee; Chun, Young Hee; Kim, Sun Hee; Cho, Kang Jin; Chang, Moon-Jeong

    2011-08-01

    In this study, we investigated the effects of the ethanol extract of aerial parts of Raphanus sativus L. (ERL) on breast cancer cell proliferation and gene expression associated with cell proliferation and apoptosis in MDA-MB-231 human breast cancer cells. The MDA-MB-231 cells were cultured in the presence or absence of various concentrations (100, 200, or 300 µg/mL) of ERL. ERL significantly decreased cell proliferation after 48 h of incubation (P < 0.05). The protein and mRNA expression of ErbB(2) were decreased significantly in a dose-dependent manner (P < 0.05). The protein expression of ErbB(3) was decreased significantly at an ERL concentration of 300 µg/mL (P < 0.05), and mRNA expression of ErbB(3) was decreased significantly in a dose-dependent manner (P < 0.05). The protein expression of Akt was decreased significantly at the ERL concentration of 200 µg/mL (P < 0.05), and the protein expression of pAkt was decreased significantly in a dose-dependent manner (P < 0.05). The mRNA expression of Akt was decreased significantly at the ERL concentration of 200 µg/mL ERL (P < 0.05). The protein and mRNA expression of Bax were increased significantly at ERL concentrations of 200 µg/mL or higher (P < 0.05). The protein expression of Bcl(2) was increased significantly at ERL concentrations of 100 µg/mL or higher (P < 0.05), and mRNA expression of Bcl(2) was increased significantly at an ERL concentration of 300 µg/mL (P < 0.05). In conclusion, we suggest that Raphanus sativus, L. inhibits cell proliferation via the ErbB-Akt pathway in MDA-MB-231 cells.

  15. Synergistic anti-cancer effects of grape seed extract and conventional cytotoxic agent doxorubicin against human breast carcinoma cells.

    PubMed

    Sharma, Girish; Tyagi, Anil K; Singh, Rana P; Chan, Daniel C F; Agarwal, Rajesh

    2004-05-01

    With an approach to enhance the efficacy of chemotherapy agents against breast cancer treatment, here, we investigated the anti-cancer effects of grape seed extract (GSE) and doxorubicin (Dox), either alone or in combination, in estrogen receptor-positive MCF-7 and receptor-negative MDA-MB468 human breast carcinoma cells. GSE (25-200 micro g/ml) treatment of cells resulted in 16-72% growth inhibition and 9-33% cell death, in a dose- and a time-dependent manner. In other studies, Dox (10-100 nM) treatment showed 23-96% growth inhibition and 10-55% cell death. Based on these results, several combinations of GSE (25-100 micro g/ml) with Dox (10-75 nM) were next assessed for their synergistic, additive and/or antagonistic efficacy towards cell growth inhibition and death. In both MCF-7 and MDA-MB468 cells, a combination of 100 micro g/ml GSE with 25-75 nM Dox treatment for 48 h showed a strong synergistic effect [combination index (CI) < 0.5] in cell growth inhibition, but mostly an additive effect (CI approximately 1) in cell death. In cell-cycle progression studies, GSE plus Dox combination resulted in a moderate increase in G1 arrest in MCF-7 cells compared to each agent alone. GSE plus Dox combination showed a very strong and significant G1 arrest in MDA-MB468 cells when compared with Dox alone, however, it was less than that observed with GSE alone. In quantitative apoptosis studies, GSE and Dox alone and in combination showed comparable apoptotic death of MCF-7 cells, however, a combination of the two was inhibitory to Dox induced apoptosis in MDA-MB468 cells. This was further confirmed in another estrogen receptor-negative MDA-MB231 cell line, in which GSE and Dox combination strongly inhibited cell growth but did not show any increase in apoptotic cell death caused by Dox. Together, these results suggest a strong possibility of synergistic efficacy of GSE and Dox combination for breast cancer treatment, independent of estrogen receptor status of the cancer cell.

  16. The role of bicarbonate in regulatory volume decrease (RVD) in the epithelial-derived human breast cancer cell line ZR-75-1.

    PubMed

    Nicholl, A J; Killey, J; Leonard, M N; Garner, C

    2002-03-01

    This study investigates the mechanisms involved in the regulatory volume decrease (RVD) in ZR-75-1 epithelial-derived human breast cancer cells. Cell volume changes were measured during osmotic shock using video imaging. In HEPES-buffered hypotonic solutions no RVD was observed; however, RVD was observed in HCO(3)(-)-buffered hypotonic solutions. Inhibition of RVD by 10 microM tamoxifen and 100 microM DIDS (inhibitors of volume-regulated anion channels; VRAC) and 2 mM TEA(+) (inhibitor of K(+) channels) indicates a role for these channels. In HCO(3)(-)-buffered Cl(-)-free solutions RVD was partially abolished indicating that HCO(3)(-) efflux can support RVD but also may have another role. Further experiments investigated whether HCO(3)(-) assists in the accumulation of Cl(-) via Cl(-)-HCO(3)(-) exchange. Regulatory volume increase (RVI) was also HCO(3)(-)-dependent and was inhibited by 500 microM DIDS and 10 microM 5-( N, N-dimethyl)-amiloride (DMA) indicating a role for coupled Cl(-)-HCO(3)(-) and Na(+)-H(+) exchange. Finally, in the presence of 10 microM DMA, RVD was partially inhibited providing further evidence for a role of Cl(-)-HCO(3)(-) exchange. Thus RVD in ZR-75-1 cells involves the activation of VRAC and K(+) channels. RVD is HCO(3)(-)-dependent and HCO(3)(-) efflux through VRAC appears to contribute directly to RVD. HCO(3)(-), however, also has another role in facilitating Cl(-) accumulation via Cl(-)-HCO(3)(-) exchange.

  17. Ultrasonographic observation of the breast in early postmenopausal women during therapy with Cimicifuga foetida extract and sequential therapy with estrogen and progestin.

    PubMed

    Gaowa, Sharen; Sun, Ai-Jun; Jiang, Ying; He, Fa-Wei; Zheng, Ting-Ping; Wang, Ya-Ping

    2015-04-20

    It is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women. This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment. In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum target check. In early

  18. HET0016, a Selective Inhibitor of 20-HETE Synthesis, Decreases Pro-Angiogenic Factors and Inhibits Growth of Triple Negative Breast Cancer in Mice

    PubMed Central

    Borin, Thaiz Ferraz; Zuccari, Debora A. P. C.; Jardim-Perassi, Bruna V.; Ferreira, Lívia C.; Iskander, A. S. M.; Varma, Nadimpalli Ravi S.; Shankar, Adarsh; Guo, Austin M.; Scicli, Guillermo; Arbab, Ali S.

    2014-01-01

    A selective inhibitor of 20-HETE synthesis, HET0016, has been reported to inhibit angiogenesis. 20-HETE has been known as a second mitogenic messenger of angiogenesis inducing growth factors. HET0016 effects were analyzed on MDA-MB-231 derived breast cancer in mouse and in vitro cell line. MDA-MB-231 tumor cells were implanted in animals’ right flank and randomly assigned to early (1 and 2), starting treatments on day 0, or delayed groups (3 and 4) on day 8 after implantation of tumor. Animals received HET0016 (10 mg/kg) treatment via intraperitoneal injection for 5 days/week for either 3 or 4 weeks. Control group received vehicle treatment. Tumor sizes were measured on days 7, 14, 21, and 28 and the animals were euthanized on day 22 and 29. Proteins were extracted from the whole tumor and from cells treated with 10 µM HET0016 for 4 and 24 hrs. Protein array kits of 20 different cytokines/factors were used. ELISA was performed to observe the HIF-1α and MMP-2 protein expression. Other markers were confirmed by IHC. HET0016 significantly inhibited tumor growth in all treatment groups at all-time points compared to control (p<0.05). Tumor growth was completely inhibited on three of ten animals on early treatment group. Treatment groups showed significantly lower expression of pro-angiogenic factors compared to control at 21 days; however, there was no significant difference in HIF-1α expression after treatments. Similar results were found in vitro at 24 hrs of HET0016 treatment. After 28 days, significant increase of angiogenin, angiopoietin-1/2, EGF-R and IGF-1 pro-angiogenic factors were found (p<0.05) compared to control, as well as an higher intensity of all factors were found when compared to that of 21 day’s data, suggesting a treatment resistance. HET0016 inhibited tumor growth by reducing expression of different set of pro-angiogenic factors; however, a resistance to treatment seemed to happen after 21 days. PMID:25549350

  19. HET0016, a selective inhibitor of 20-HETE synthesis, decreases pro-angiogenic factors and inhibits growth of triple negative breast cancer in mice.

    PubMed

    Borin, Thaiz Ferraz; Zuccari, Debora A P C; Jardim-Perassi, Bruna V; Ferreira, Lívia C; Iskander, A S M; Varma, Nadimpalli Ravi S; Shankar, Adarsh; Guo, Austin M; Scicli, Guillermo; Arbab, Ali S

    2014-01-01

    A selective inhibitor of 20-HETE synthesis, HET0016, has been reported to inhibit angiogenesis. 20-HETE has been known as a second mitogenic messenger of angiogenesis inducing growth factors. HET0016 effects were analyzed on MDA-MB-231 derived breast cancer in mouse and in vitro cell line. MDA-MB-231 tumor cells were implanted in animals' right flank and randomly assigned to early (1 and 2), starting treatments on day 0, or delayed groups (3 and 4) on day 8 after implantation of tumor. Animals received HET0016 (10 mg/kg) treatment via intraperitoneal injection for 5 days/week for either 3 or 4 weeks. Control group received vehicle treatment. Tumor sizes were measured on days 7, 14, 21, and 28 and the animals were euthanized on day 22 and 29. Proteins were extracted from the whole tumor and from cells treated with 10 µM HET0016 for 4 and 24 hrs. Protein array kits of 20 different cytokines/factors were used. ELISA was performed to observe the HIF-1α and MMP-2 protein expression. Other markers were confirmed by IHC. HET0016 significantly inhibited tumor growth in all treatment groups at all-time points compared to control (p<0.05). Tumor growth was completely inhibited on three of ten animals on early treatment group. Treatment groups showed significantly lower expression of pro-angiogenic factors compared to control at 21 days; however, there was no significant difference in HIF-1α expression after treatments. Similar results were found in vitro at 24 hrs of HET0016 treatment. After 28 days, significant increase of angiogenin, angiopoietin-1/2, EGF-R and IGF-1 pro-angiogenic factors were found (p<0.05) compared to control, as well as an higher intensity of all factors were found when compared to that of 21 day's data, suggesting a treatment resistance. HET0016 inhibited tumor growth by reducing expression of different set of pro-angiogenic factors; however, a resistance to treatment seemed to happen after 21 days.

  20. Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis

    PubMed Central

    Arya, Rakesh K.; Singh, Akhilesh; Yadav, Navneet K.; Cheruvu, Srikanth H.; Hossain, Zakir; Meena, Sanjeev; Maheshwari, Shrankhla; Singh, Anup K.; Shahab, Uzma; Sharma, Chetan; Singh, Kavita; Narender, Tadigoppula; Mitra, Kalyan; Arya, Kamal R.; Singh, Rama K.; Gayen, Jiaur R.; Datta, Dipak

    2015-01-01

    Major challenges for current therapeutic strategies against breast cancer are associated with drug-induced toxicities. Considering the immense potential of bioactive phytochemicals to deliver non-toxic, efficient anti-cancer therapeutics, we performed bio-guided fractionation of Eclipta alba extract and discovered that particularly the chloroform fraction of Eclipta alba (CFEA) is selectively inducing cytotoxicity to breast cancer cells over non-tumorigenic breast epithelial cells. Our unbiased mechanistic hunt revealed that CFEA specifically activates the intrinsic apoptotic pathway by disrupting the mitochondrial membrane potential, upregulating Hsp60 and downregulating the expression of anti-apoptotic protein XIAP. By utilizing Hsp60 specific siRNA, we identified a novel pro-apoptotic role of Hsp60 and uncovered that following CFEA treatment, upregulated Hsp60 is localized in the endoplasmic reticulum (ER). To our knowledge, this is the first evidence of ER specific localization of Hsp60 during cancer cell apoptosis. Further, our LC-MS approach identified that luteolin is mainly attributed for its anti-cancer activities. Moreover, oral administration of CFEA not only offers potential anti-breast cancer effects in-vivo but also mitigates tumor induced hepato-renal toxicity. Together, our studies offer novel mechanistic insight into the CFEA mediated inhibition of breast cancer and may potentially open up new avenues for further translational research. PMID:26672742

  1. The red-vine-leaf extract AS195 increases nitric oxide synthase-dependent nitric oxide generation and decreases oxidative stress in endothelial and red blood cells.

    PubMed

    Grau, Marijke; Bölck, Birgit; Bizjak, Daniel Alexander; Stabenow, Christina Julia Annika; Bloch, Wilhelm

    2016-02-01

    The red-vine-leaf extract AS195 improves cutaneous oxygen supply and the microcirculation in patients suffering from chronic venous insufficiency. Regulation of blood flow was associated to nitric oxide synthase (NOS)-dependent NO (nitric oxide) production, and endothelial and red blood cells (RBC) have been shown to possess respective NOS isoforms. It was hypothesized that AS195 positively affects NOS activation in human umbilical vein endothelial cells (HUVECs) and RBC. Because patients with microvascular disorders show increased oxidative stress which limits NO bioavailability, it was further hypothesized that AS195 increases NO bioavailability by decreasing the content of reactive oxygen species (ROS) and increasing antioxidant capacity. Cultured HUVECs and RBCs from healthy volunteers were incubated with AS195 (100 μmol/L), tert-butylhydroperoxide (TBHP, 1 mmol/L) to induce oxidative stress and with both AS195 and TBHP. Endothelial and red blood cell-nitric oxide synthase (RBC-NOS) activation significantly increased after AS195 incubation. Nitrite concentration, a marker for NO production, increased in HUVEC but decreased in RBC after AS195 application possibly due to nitrite scavenging potential of flavonoids. S-nitrosylation of RBC cytoskeletal spectrins and RBC deformability were increased after AS195 incubation. TBHP-induced ROS were decreased by AS195, and antioxidative capacity was significantly increased in AS195-treated cells. TBHP also reduced RBC deformability, but reduction was attenuated by parallel incubation with AS195. Adhesion of HUVEC was also reduced after AS195 treatment. Red-vine-leaf extract AS195 increases NOS activation and decreases oxidative stress. Both mechanisms increase NO bioavailability, improve cell function, and may thus account for enhanced microcirculation in both health and disease.

  2. Five-Year Follow-Up of Patients with Early Stage Breast Cancer After a Randomized Study Comparing Additional Treatment with Viscum Album (L.) Extract to Chemotherapy Alone

    PubMed Central

    Tröger, Wilfried; Ždrale, Zdravko; Stanković, Nikola; Matijašević, Miodrag

    2012-01-01

    Additional therapy with extracts of Viscum album [L.] (VaL) increases the quality of life of patients suffering from early stage breast cancer during chemotherapy. In the current study patients received chemotherapy, consisting of six cycles of cyclophosphamide, anthracycline, and 5-Fluoro-Uracil (CAF). Two groups also received one of two VaL extracts differing in their preparation as subcutaneous injection three times per week. A control group received CAF with no additional therapy. Six of 28 patients in one of the VaL groups and eight of 29 patients in the control group developed relapse or metastasis within 5 years. Subgroup analysis for hormone- and radiotherapy also showed no difference between groups. Additional VaL therapy during chemotherapy of early stage breast cancer patients appears not to influence the frequency of relapse or metastasis within 5 years. PMID:23150723

  3. Phyllanthus Niruri Standardized Extract Alleviates the Progression of Non-Alcoholic Fatty Liver Disease and Decreases Atherosclerotic Risk in Sprague–Dawley Rats

    PubMed Central

    Al Zarzour, Raghdaa Hamdan; Ahmad, Mariam; Asmawi, Mohd. Zaini; Kaur, Gurjeet; Al-Mansoub, Majed Ahmed; Saghir, Sultan Ayesh Mohammed; Usman, Nasiba Salisu; Al-Dulaimi, Dhamraa W.; Yam, Mun Fei

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the major global health issues, strongly correlated with insulin resistance, obesity and oxidative stress. The current study aimed to evaluate anti-NAFLD effects of three different extracts of Phyllanthus niruri (P. niruri). NAFLD was induced in male Sprague–Dawley rats using a special high-fat diet (HFD). A 50% methanolic extract (50% ME) exhibited the highest inhibitory effect against NAFLD progression. It significantly reduced hepatomegaly (16%) and visceral fat weight (22%), decreased NAFLD score, prevented fibrosis, and reduced serum total cholesterol (TC) (48%), low-density lipoprotein (LDL) (65%), free fatty acids (FFAs) (25%), alanine aminotransferase (ALT) (45%), alkaline phosphatase (ALP) (38%), insulin concentration (67%), homeostatic model assessment of insulin resistance (HOMA-IR) (73%), serum atherogenic ratios TC/high-density lipoprotein (HDL) (29%), LDL/HDL (66%) and (TC–HDL)/HDL (64%), hepatic content of cholesterol (43%), triglyceride (29%) and malondialdehyde (MDA) (40%) compared to a non-treated HFD group. In vitro, 50% ME of P. niruri inhibited α-glucosidase, pancreatic lipase enzymes and cholesterol micellization. It also had higher total phenolic and total flavonoid contents compared to other extracts. Ellagic acid and phyllanthin were identified as major compounds. These results suggest that P. niruri could be further developed as a novel natural hepatoprotective agent against NAFLD and atherosclerosis. PMID:28718838

  4. Schinus terebinthifolius Raddi extract and linoleic acid from Passiflora edulis synergistically decrease melanin synthesis in B16 cells and reconstituted epidermis.

    PubMed

    Jorge, A T S; Arroteia, K F; Santos, I A; Andres, E; Medina, S P H; Ferrari, C R; Lourenço, C B; Biaggio, R M T T; Moreira, P L

    2012-10-01

    Several treatments for skin whitening are available today, but few of them are completely adequate, especially owing to the carcinogenic potential attributed to classical drugs like hydroquinone, arbutin and kojic acid. To provide an alternative and safer technology for whitening, we developed two botanical compounds originated from Brazilian biodiversity, an extract of Schinus terebinthifolius Raddi and a linoleic acid fraction isolated from Passiflora edulis oil. The whitening effect of these compounds was assessed using biochemical assays and in vitro models including cellular assays and equivalent skin. The results showed that S. terebinthifolius Raddi extract is able to reduce the tyrosinase activity in vitro, and the combination of this extract with linoleic acid is able to decrease the level of melanin produced by B16 cells cultured with melanocyte-stimulating hormone. Furthermore, melanin was also reduced in human reconstituted epidermis (containing melanocytes) treated with the compounds. The combination of the compounds may provide a synergistic positive whitening effect rather than their isolated use. Finally, we demonstrated that the performance of these mixed compounds is comparable to classical molecules used for skin whitening, as kojic acid. This new natural mixture could be considered an alternative therapeutic agent for treating hyperpigmentation and an effective component in whitening cosmetics.

  5. Breast cancer mitosis detection in histopathological images with spatial feature extraction

    NASA Astrophysics Data System (ADS)

    Albayrak, Abdülkadir; Bilgin, Gökhan

    2013-12-01

    In this work, cellular mitosis detection in histopathological images has been investigated. Mitosis detection is very expensive and time consuming process. Development of digital imaging in pathology has enabled reasonable and effective solution to this problem. Segmentation of digital images provides easier analysis of cell structures in histopathological data. To differentiate normal and mitotic cells in histopathological images, feature extraction step is very crucial step for the system accuracy. A mitotic cell has more distinctive textural dissimilarities than the other normal cells. Hence, it is important to incorporate spatial information in feature extraction or in post-processing steps. As a main part of this study, Haralick texture descriptor has been proposed with different spatial window sizes in RGB and La*b* color spaces. So, spatial dependencies of normal and mitotic cellular pixels can be evaluated within different pixel neighborhoods. Extracted features are compared with various sample sizes by Support Vector Machines using k-fold cross validation method. According to the represented results, it has been shown that separation accuracy on mitotic and non-mitotic cellular pixels gets better with the increasing size of spatial window.

  6. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    SciTech Connect

    Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel Ángel

    2014-05-09

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

  7. Low-dose radiation decreases tumor progression via the inhibition of the JAK1/STAT3 signaling axis in breast cancer cell lines

    PubMed Central

    Kaushik, Neha; Kim, Min-Jung; Kim, Rae-Kwon; Kumar Kaushik, Nagendra; Seong, Ki Moon; Nam, Seon-Young; Lee, Su-Jae

    2017-01-01

    Breast cancer is a widely distributed type of cancer in women worldwide, and tumor relapse is the major cause of breast cancer death. In breast cancers, the acquisition of metastatic ability, which is responsible for tumor relapse and poor clinical outcomes, has been linked to the acquisition of the epithelial-mesenchymal transition (EMT) program and self-renewal traits (CSCs) via various signaling pathways. These phenomena confer resistance during current therapies, thus creating a major hurdle in radiotherapy/chemotherapy. The role of very low doses of radiation (LDR) in the context of EMT has not yet to be thoroughly explored. Here, we report that a 0.1 Gy radiation dose reduces cancer progression by deactivating the JAK1/STAT3 pathway. Furthermore, LDR exposure also reduces sphere formation and inhibits the self-renewal ability of breast cancer cells, resulting in an attenuated CD44+/CD24− population. Additionally, in vivo findings support our data, providing evidence that LDR is a promising option for future treatment strategies to prevent cancer metastasis in breast cancer cases. PMID:28240233

  8. Low-dose radiation decreases tumor progression via the inhibition of the JAK1/STAT3 signaling axis in breast cancer cell lines.

    PubMed

    Kaushik, Neha; Kim, Min-Jung; Kim, Rae-Kwon; Kumar Kaushik, Nagendra; Seong, Ki Moon; Nam, Seon-Young; Lee, Su-Jae

    2017-02-27

    Breast cancer is a widely distributed type of cancer in women worldwide, and tumor relapse is the major cause of breast cancer death. In breast cancers, the acquisition of metastatic ability, which is responsible for tumor relapse and poor clinical outcomes, has been linked to the acquisition of the epithelial-mesenchymal transition (EMT) program and self-renewal traits (CSCs) via various signaling pathways. These phenomena confer resistance during current therapies, thus creating a major hurdle in radiotherapy/chemotherapy. The role of very low doses of radiation (LDR) in the context of EMT has not yet to be thoroughly explored. Here, we report that a 0.1 Gy radiation dose reduces cancer progression by deactivating the JAK1/STAT3 pathway. Furthermore, LDR exposure also reduces sphere formation and inhibits the self-renewal ability of breast cancer cells, resulting in an attenuated CD44(+)/CD24(-) population. Additionally, in vivo findings support our data, providing evidence that LDR is a promising option for future treatment strategies to prevent cancer metastasis in breast cancer cases.

  9. Oxidised LDL levels decreases after the consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet.

    PubMed

    Ibero-Baraibar, I; Abete, I; Navas-Carretero, S; Massis-Zaid, A; Martinez, J A; Zulet, M A

    2014-04-01

    Cocoa flavanols are recognised by their favourable antioxidant and vascular effects. This study investigates the influence on health of the daily consumption of ready-to-eat meals supplemented with cocoa extract within a hypocaloric diet, on middle-aged overweight/obese subjects. Fifty healthy male and female middle-aged volunteers [57.26 ± 5.24 years and body mass index (BMI) 30.59 ± 2.33 kg/m(2)] were recruited to participate in a 4 week randomised, parallel and double-blind study. After following 3 days on a low-polyphenol diet, 25 volunteers received meals supplemented with 1.4 g of cocoa extract (645.3 mg of polyphenols) and the other 25 participants received control meals, within a 15% energy restriction diet. On the 4th week of intervention individuals in both dietary groups improved (p < 0.05) anthropometric, body composition, blood pressure and blood biochemical measurements. Oxidised LDL cholesterol (oxLDL), showed a higher reduction (p = 0.030) in the cocoa group. Moreover, myeloperoxidase (MPO) levels decreased only in the cocoa supplemented group (p = 0.007). Intercellular Adhesion Molecule-1 (sICAM-1) decreased significantly in both groups, while Vascular Cell Adhesion Molecule-1 (sVCAM-1) did not present differences after the 4 weeks of intervention. Interestingly, cocoa intake showed a different effect by gender, presenting more beneficial effects in men. The consumption of cocoa extract as part of ready-to-eat meals and within a hypocaloric diet improved oxidative status (oxLDL) in middle-aged subjects, being most remarkable in males. Registered at www.clinicaltrials.gov (NCT01596309). Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Hydro-alcoholic extract of Raphanus sativus L. var niger attenuates bleomycin-induced pulmonary fibrosis via decreasing transforming growth factor β1 level.

    PubMed

    Asghari, Mohammad Hossein; Hobbenaghi, Rahim; Nazarizadeh, Ali; Mikaili, Peyman

    2015-01-01

    Pulmonary fibrosis is a progressive disease of the lungs, which leads to death in human. It has been suggested that transforming growth factor beta 1 (TGF-β1) together with oxidative stress play a central role in the pathogenesis of the ailment. The objective of this study was to evaluate the possible curative effects of black radish, Raphanus sativus L. var niger (RSN) on bleomycine (BLM) -induced pulmonary fibrosis in a rat model. In this study, thirty-six male Wistar rats were divided into six groups, including: (I) positive (BLM) control group, (II) negative (normal saline) control group, (III) sham group (R. sativus extract 150 mg/kg), and (IV-VI) treatment groups. In order to induce pulmonary fibrosis, four groups were treated with a single dose of BLM sulfate (7.5 U/kg) through intratracheal instillation. Treatment groups (IV-VI) received RSN extract (75, 150, and 300 mg/kg) orally a week before and two weeks after the administration of BLM. At the end of the treatment course, blood and lung tissue samples were taken and the measurement of TGF-β1 and histopathological examination of the lung tissues performed. The results showed that RSN, at 300 mg/kg dose, could significantly decrease the serum level of TGF-β1 and severity of the histological lesions as compared to the positive control group. The results of the current study indicate that the components present in the extract can remarkably prevent the aggravation of pulmonary fibrosis via decreasing TGF-β1 level.

  11. Hydro-alcoholic extract of Raphanus sativus L. var niger attenuates bleomycin-induced pulmonary fibrosis via decreasing transforming growth factor β1 level

    PubMed Central

    Asghari, Mohammad Hossein; Hobbenaghi, Rahim; Nazarizadeh, Ali; Mikaili, Peyman

    2015-01-01

    Pulmonary fibrosis is a progressive disease of the lungs, which leads to death in human. It has been suggested that transforming growth factor beta 1 (TGF-β1) together with oxidative stress play a central role in the pathogenesis of the ailment. The objective of this study was to evaluate the possible curative effects of black radish, Raphanus sativus L. var niger (RSN) on bleomycine (BLM) -induced pulmonary fibrosis in a rat model. In this study, thirty-six male Wistar rats were divided into six groups, including: (I) positive (BLM) control group, (II) negative (normal saline) control group, (III) sham group (R. sativus extract 150 mg/kg), and (IV-VI) treatment groups. In order to induce pulmonary fibrosis, four groups were treated with a single dose of BLM sulfate (7.5 U/kg) through intratracheal instillation. Treatment groups (IV-VI) received RSN extract (75, 150, and 300 mg/kg) orally a week before and two weeks after the administration of BLM. At the end of the treatment course, blood and lung tissue samples were taken and the measurement of TGF-β1 and histopathological examination of the lung tissues performed. The results showed that RSN, at 300 mg/kg dose, could significantly decrease the serum level of TGF-β1 and severity of the histological lesions as compared to the positive control group. The results of the current study indicate that the components present in the extract can remarkably prevent the aggravation of pulmonary fibrosis via decreasing TGF-β1 level. PMID:26752991

  12. Nuclear T-STAR protein expression correlates with HER2 status, hormone receptor negativity and prolonged recurrence free survival in primary breast cancer and decreased cancer cell growth in vitro.

    PubMed

    Sernbo, Sandra; Borrebaeck, Carl A K; Uhlén, Mathias; Jirström, Karin; Ek, Sara

    2013-01-01

    T-STAR (testis-signal transduction and activation of RNA) is an RNA binding protein, containing an SH3-binding domain and thus potentially playing a role in integration of cell signaling and RNA metabolism. The specific function of T-STAR is unknown and its implication in cancer is poorly characterized. Expression of T-STAR has been reported in human testis, muscle and brain tissues, and is associated with a growth-inhibitory role in immortalized fibroblasts. The aim of this paper was to investigate the functional role of T-STAR through (i) survival analysis of patients with primary invasive breast cancer and (ii) experimental evaluation of the effect of T-STAR on breast cancer cell growth. T-STAR protein expression was analysed by immunohistochemistry (IHC) in tissue microarrays with tumors from 289 patients with primary invasive breast cancer, and correlations to clinicopathological characteristics, recurrence-free and overall survival (RFS and OS) and established tumor markers such as HER2 and ER status were evaluated. In addition, the function of T-STAR was investigated using siRNA-mediated knock-down and overexpression of the gene in six breast cancer cell lines. Of the tumors analysed, 86% showed nuclear T-STAR expression, which was significantly associated with an improved RFS and strongly associated with positive HER2 status and negative hormone receptor status. Furthermore, experimental data showed that overexpression of T-STAR decreased cellular growth while knock-down increased it, as shown both by thymidine incorporation and metabolic activity. In summary, we demonstrate that T-STAR protein expression correlates with an improved RFS in primary breast cancer. This is supported by functional data, indicating that T-STAR regulation is of importance both for breast cancer biology and clinical outcome but future studies are needed to determine a potential role in patient stratification.

  13. Polyphenol-rich Avicennia marina leaf extracts induce apoptosis in human breast and liver cancer cells and in a nude mouse xenograft model.

    PubMed

    Huang, Cheng; Lu, Chung-Kuang; Tu, Ming-Chin; Chang, Jia-Hua; Chen, Yen-Ju; Tu, Yu-Hsuan; Huang, Hsiu-Chen

    2016-06-14

    Avicennia marina is the most abundant and common mangrove species and has been used as a traditional medicine for skin diseases, rheumatism, ulcers, and smallpox. However, its anticancer activities and polyphenol contents remain poorly characterized. Thus, here we investigated anticancer activities of secondary A. marina metabolites that were purified by sequential soxhlet extraction in water, ethanol, methanol, and ethyl acetate (EtOAc). Experiments were performed in three human breast cancer cell lines (AU565, MDA-MB-231, and BT483), two human liver cancer cell lines (HepG2 and Huh7), and one normal cell line (NIH3T3). The chemotherapeutic potential of A. marina extracts was evaluated in a xenograft mouse model. The present data show that EtOAc extracts of A. marina leaves have the highest phenolic and flavonoid contents and anticancer activities and, following column chromatography, the EtOAc fractions F2-5, F3-2-9, and F3-2-10 showed higher cytotoxic effects than the other fractions. 1H-NMR and 13C-NMR profiles indicated that the F3-2-10 fraction contained avicennones D and E. EtOAc extracts of A. marina leaves also suppressed xenograft MDA-MB-231 tumor growth in nude mice, suggesting that EtOAc extracts of A. marina leaves may provide a useful treatment for breast cancer.

  14. Synergistic effect of apple extracts and quercetin 3-beta-d-glucoside combination on antiproliferative activity in MCF-7 human breast cancer cells in vitro.

    PubMed

    Yang, Jun; Liu, Rui Hai

    2009-09-23

    Breast cancer is the most frequently diagnosed cancer in women. An alternative strategy to reduce the risk of cancer is through dietary modification. Although phytochemicals naturally occur as complex mixtures, little information is available regarding possible additive, synergistic, or antagonistic interactions among compounds. The antiproliferative activity of apple extracts and quercetin 3-beta-d-glucoside (Q3G) was assessed by measurement of the inhibition of MCF-7 human breast cancer cell proliferation. Cell cytotoxicity was determined by the methylene blue assay. The two-way combination of apple plus Q3G was conducted. In this two-way combination, the EC(50) values of apple extracts and Q3G were 2- and 4-fold lower, respectively, than those of apple extracts and Q3G alone. The combination index (CI) values at 50 and 95% inhibition rates were 0.76 +/- 0.16 and 0.42 +/- 0.10, respectively. The dose-reduction index (DRI) values of the apple extracts and Q3G to achieve a 50% inhibition effect were reduced by 2.03 +/- 0.55 and 4.28 +/- 0.39-fold, respectively. The results suggest that the apple extracts plus Q3G combination possesses a synergistic effect in MCF-7 cell proliferation.

  15. Polyphenol-rich Avicennia marina leaf extracts induce apoptosis in human breast and liver cancer cells and in a nude mouse xenograft model

    PubMed Central

    Tu, Ming-Chin; Chang, Jia-Hua; Chen, Yen-Ju; Tu, Yu-Hsuan; Huang, Hsiu-Chen

    2016-01-01

    Avicennia marina is the most abundant and common mangrove species and has been used as a traditional medicine for skin diseases, rheumatism, ulcers, and smallpox. However, its anticancer activities and polyphenol contents remain poorly characterized. Thus, here we investigated anticancer activities of secondary A. marina metabolites that were purified by sequential soxhlet extraction in water, ethanol, methanol, and ethyl acetate (EtOAc). Experiments were performed in three human breast cancer cell lines (AU565, MDA-MB-231, and BT483), two human liver cancer cell lines (HepG2 and Huh7), and one normal cell line (NIH3T3). The chemotherapeutic potential of A. marina extracts was evaluated in a xenograft mouse model. The present data show that EtOAc extracts of A. marina leaves have the highest phenolic and flavonoid contents and anticancer activities and, following column chromatography, the EtOAc fractions F2-5, F3-2-9, and F3-2-10 showed higher cytotoxic effects than the other fractions. 1H-NMR and 13C-NMR profiles indicated that the F3-2-10 fraction contained avicennones D and E. EtOAc extracts of A. marina leaves also suppressed xenograft MDA-MB-231 tumor growth in nude mice, suggesting that EtOAc extracts of A. marina leaves may provide a useful treatment for breast cancer. PMID:27078842

  16. Targeting beta-Catenin signaling to induce apoptosis in human breast cancer cells by z-Guggulsterone and Gugulipid extract of Ayurvedic medicine plant Commiphora mukul

    PubMed Central

    2013-01-01

    Background z-Guggulsterone (z-Gug) and Gugulipid (GL) have been used to treat a variety of ailments. We now report their anti-cancer effect and mechanism against human breast cancer. Methods Using the human estrogen receptor-positive (MCF-7) and triple-negative (MDA-MB-231) breast cancer cells as well as the normal human mammary epithelial cell line (HMEC), we evaluated the anti-breast-cancer efficacy and apoptosis inducing activity of GL. We determined the cellular and molecular mechanism of GL-inhibited breast cancer cell growth. Results GL significantly inhibited growth of MCF-7 and MDA-MB-231 cells with an IC50~2 μM at pharmacologically relevant concentrations standardized to its major active constituent z-Gug. The GL-induced growth inhibition correlated with apoptosis induction as evidenced by an increase in cytoplasmic histone-associated DNA fragmentation and caspase 3 activity. The GL-induced apoptosis was associated with down-regulation of the β-Catenin signaling pathway. The decreased expression of Wnt/β-Catenin targeting genes, such as cyclin D1, C-myc and survivin, and the inhibition of the activity of the transcription factor (T-cell factor 4, TCF-4) were observed in GL-treated breast cancer cells. The GL treatment resulted in a significant reduction of β-Catenin /TCF-4 complex in both of the cancer cells. The GL-induced apoptotic cell death was significantly enhanced by RNA Interference of β-Catenin and TCF-4. On the other hand, the normal human mammary epithelial cell HMEC, compared with the human breast cancer cells, is significantly more resistant to growth inhibition and apoptosis induction by GL. Conclusion The present study indicates that the β-Catenin signaling pathway is the target for GL-induced growth inhibition and apoptosis in human breast cancer. PMID:23914993

  17. Combined treatment of betulinic acid, a PTP1B inhibitor, with Orthosiphon stamineus extract decreases body weight in high-fat-fed mice.

    PubMed

    Choi, Yoon-Jung; Park, So-Young; Kim, Jong-Yeon; Won, Kyu-Chang; Kim, Bo-Ra; Son, Jong-Keun; Lee, Seung-Ho; Kim, Yong-Woon

    2013-01-01

    Leptin resistance is a common feature of obesity and is accompanied by hyperleptinemia. Although leptin sensitizers improve leptin resistance, they also decrease plasma leptin levels that attenuate the leptin-associated antiobesity effect. We hypothesized that the combinational treatment of leptin sensitizer and endogenous leptin expression stimulant would synergistically induce an antiobesity effect in high-fat-fed obese animals. Betulinic acid (BA) isolated from Saussurea lappa suppressed the hypothalamic protein tyrosine phosphatase 1B in mice and enhanced the antiobesity effect of leptin in obese rats. Ethanol extract of Orthosiphon stamineus (OS) induced leptin expressions in both 3T3-L1 adipocytes and mice in a dose-dependent manner. To evaluate our hypothesis, we treated obese mice induced by 6 weeks of high-fat-diet feeding with BA and OS for 2 weeks. Although BA or OS alone did not decrease body weight in obese mice, the combinational treatment of BA and OS decreased body weight significantly compared to either BA- or OS-treated obese mice. These results suggest that combinational treatment of BA and OS would be effective for the treatment of obesity.

  18. Hormetic/cytotoxic effects of Nigella sativa seed alcoholic and aqueous extracts on MCF-7 breast cancer cells alone or in combination with doxorubicin.

    PubMed

    Mahmoud, Sherif S; Torchilin, Vladmir P

    2013-07-01

    In this study, we investigate the possible cytotoxic effects of different Nigella sativa seed extracts on human MCF-7 breast cancer cells and screening the effects of a wide range of extracts concentrations and their application as an adjuvant therapy to doxorubicin. The results obtained showed that the cytotoxic solvent dimethyl sulfoxide can be used for permeation assay in concentration range 697.5-0.341 mmol/ml without affecting the viability of MCF-7 cells. N. sativa lipid extract is cytotoxic to MCF-7 cells with LC50 of 2.72 ± 0.232 mg/ml, while its aqueous extract cytotoxicity exhibited when the applied concentration is high as ≈ 50 mg/ml. The results of this study reveal for the first time that low concentrations of aqueous extract of the seed has a hormetic rather than cytotoxic effect. It is also possible to use cell culture medium or bovine serum to dilute the oil extract for the permeation assay. In conclusion, N. sativa aqueous extract should not be used as antitumor compound by its own. The oil is a promising antitumor compound and its cytotoxicity was greatly enhanced with its nanoemulsion formulation. Antitumor activity of doxorubicin was enhanced, as a function of time, when N. sativa extracts were involved as adjunct therapeutic compounds. Adding doxorubicin to the prepared lipid nanoemulsion has a beneficial impact to their bioactivity. These doxorubicin-N. sativa lipid nanoemulsion are promising and potential therapeutic modality.

  19. Synergistic cytotoxicity of red beetroot (Beta vulgaris L.) extract with doxorubicin in human pancreatic, breast and prostate cancer cell lines.

    PubMed

    Kapadia, Govind J; Rao, G Subba; Ramachandran, Cheppail; Iida, Akira; Suzuki, Nobutaka; Tokuda, Harukuni

    2013-06-26

    Although a wide variety of cytotoxic plant extracts and phytochemicals are known to act synergistically with anticancer drug doxorubicin (D), their clinical application is hindered by safety concerns of such combination therapy. Our earlier studies showed that red beetroot (Beta vulgaris L.) extract (B), approved by Food and Drug Administration and European Union as red food color E162, reduced multi-organ tumor formations in various animal models when administered in drinking water. This led us to postulate that a long-term daily exposure to low doses of B through diet might be safe and sufficient to produce cancer chemopreventive effect in humans. Further, our recent comparative cytotoxic investigation with B and D in several human cancer cell lines indicated their potential for synergistic activity. Since B is considered safe for human use with no known toxicity, we conducted the present study to evaluate its synergistic antiproliferative activity with D against pancreatic (PaCa), breast (MCF-7) and prostate (PC-3) tumor cells of human origin. Different concentrations of B and D (0.29-290 μg/ml) and in various combinations (B:D ratio = 1:0, 1:1, 5:1, 1:5 and 0:1) were tested for cytotoxic effects against the three cancer cells. The viability of cells was assessed after 72 h incubation with various combinations of B and D using the trypan-blue staining method. The cytotoxic data were analyzed by the combination index method of Chou and Talalay to establish synergy between B and D. The results indicated that an overall positive reduction in drug concentration was achieved by D when combined with B in its cytotoxicity profile in the three human cancer cells tested. The synergistic cytotoxicity was best when the B:D ratio of 1:5 was used in PaCa cells at IC50, IC75 and IC90 dose levels and in MCF-7 cells at IC90 dose level. These results warrant further studies on the potential of red beetroot extract-doxorubicin combination in treating human cancers.

  20. Comparison of tamoxifen with edible seaweed (Eucheuma cottonii L.) extract in suppressing breast tumor.

    PubMed

    Shamsabadi, Fatemeh T; Khoddami, Ali; Fard, Samaneh Ghasemi; Abdullah, Rasedee; Othman, Hemn Hassan; Mohamed, Suhaila

    2013-01-01

    The tropical edible red seaweed (Eucheuma cottonii L.) is rich in nutrients and polyphenolic compounds that may suppress cancer through its antioxidant and antiproliferative properties. The study reports on rat mammary tumor suppression and tissue antioxidant status modulation by E. cottonii ethanol extract (ECE). The effect of orally administered ECE (100 mg/kg body-weight) was compared with that of tamoxifen (10 mg/kg body-weight). Rat was induced to develop mammary tumor with subcutaneous injection of LA-7 cells (6 × 10(6) cells/rat). The ECE was more effective than tamoxifen in suppressing tumor growth (27%), improving tissues (plasma, liver, and kidney) malondialdehyde concentrations, superoxide dismutase activity and erythrocyte glutathione concentrations (P < 0.05). Unlike tamoxifen, the ECE displayed little toxicity to the liver and kidneys. The ECE exhibited strong anticancer effect with enzyme modulating properties, suggesting its potential as a suppressing agent for mammary gland tumor.

  1. Diffuse boundary extraction of breast masses on ultrasound by leak plugging

    SciTech Connect

    Cary, T.W.; Conant, E.F.; Arger, P.H.; Sehgal, C.M.

    2005-11-15

    We propose a semiautomated seeded boundary extraction algorithm that delineates diffuse region boundaries by finding and plugging their leaks. The algorithm not only extracts boundaries that are partially diffuse, but in the process finds and quantifies those parts of the boundary that are diffuse, computing local sharpness measurements for possible use in computer-aided diagnosis. The method treats a manually drawn seed region as a wellspring of pixel 'fluid' that flows from the seed out towards the boundary. At indistinct or porous sections of the boundary, the growing region will leak into surrounding tissue. By changing the size of structuring elements used for growing, the algorithm changes leak properties. Since larger elements cannot leak as far from the seed, they produce compact, less detailed boundary approximations; conversely, growing from smaller elements results in less constrained boundaries with more local detail. This implementation of the leak plugging algorithm decrements the radius of structuring disks and then compares the regions grown from them as they increase in both area and boundary detail. Leaks are identified if the outflows between grown regions are large compared to the areas of the disks. The boundary is plugged by masking out leaked pixels, and the process continues until one-pixel-radius resolution. When tested against manual delineation on scans of 40 benign masses and 40 malignant tumors, the plugged boundaries overlapped and correlated well in area with manual tracings, with mean overlap of 0.69 and area correlation R{sup 2} of 0.86, but the algorithm's results were more reproducible.

  2. Socioeconomic deprivation worsens the outcomes of Italian women with hormone receptor-positive breast cancer and decreases the possibility of receiving standard care.

    PubMed

    Di Salvo, Francesca; Caranci, Nicola; Spadea, Teresa; Zengarini, Nicolas; Minicozzi, Pamela; Amash, Hade; Fusco, Mario; Stracci, Fabrizio; Falcini, Fabio; Cirilli, Claudia; Candela, Giuseppina; Cusimano, Rosanna; Tumino, Rosario; Sant, Milena

    2017-09-15

    Socioeconomic factors influence access to cancer care and survival. This study investigated the role of socioeconomic status on the risk of breast cancer recurrence and on the delivery of appropriate cancer care (sentinel lymph node biopsy and breast-conserving surgery plus radiotherapy), by patients' age and hormone receptor status. 3,462 breast cancer cases diagnosed in 2003-2005 were selected from 7 Italian cancer registries and assigned to a socioeconomic tertile on the basis of the deprivation index of their census tract. Multivariable models were applied to assess the delivery of sentinel lymph node biopsy and of breast-conserving surgery plus radiotherapy within socioeconomic tertiles. In the 1,893 women younger than 65 years, the 5-year risk of recurrence was higher in the most deprived group than in the least deprived, but this difference was not significant (16.4% vs. 12.9%, log-rank p=0.08); no difference was seen in women ≥65 years. Among the 2,024 women with hormone receptor-positive cancer, the 5-year risk was significantly higher in the most deprived group than in the least deprived one (13.0% vs. 8.9%, p=0.04); no difference was seen in cases of hormone receptor-negative cancer. The most deprived women were less likely than the least deprived women to receive sentinel lymph node biopsy (adjusted odds ratio (ORa), 0.69; 95% CI, 0.56-0.86) and to undergo breast-conserving surgery plus radiotherapy (ORa=0.66; 95% CI, 0.51-0.86). Conclusions: Socioeconomic inequalities affect the risk of recurrence, among patients with hormone receptor-positive cancer, and the opportunity to receive standard care.

  3. Green tea extract decreases starch digestion and absorption from a test meal in humans: a randomized, placebo-controlled crossover study

    PubMed Central

    Lochocka, Klaudia; Bajerska, Joanna; Glapa, Aleksandra; Fidler-Witon, Ewa; Nowak, Jan K.; Szczapa, Tomasz; Grebowiec, Philip; Lisowska, Aleksandra; Walkowiak, Jaroslaw

    2015-01-01

    Green tea is known worldwide for its beneficial effects on human health. However, objective data evaluating this influence in humans is scarce. The aim of the study was to assess the impact of green tea extract (GTE) on starch digestion and absorption. The study comprised of 28 healthy volunteers, aged 19 to 28 years. In all subjects, a starch 13C breath test was performed twice. Subjects randomly ingested naturally 13C-abundant cornflakes during the GTE test (GTE 4 g) or placebo test. The cumulative percentage dose recovery (CPDR) was significantly lower for the GTE test than for the placebo test (median [interquartile range]: 11.4% [5.5–15.5] vs. 16.1% [12.7–19.5]; p = 0.003). Likewise, CPDR expressed per hour was considerably lower in each point of the measurement. In conclusion, a single dose of green tea extract taken with a test meal decreases starch digestion and absorption. PMID:26226166

  4. Caffeic Acid phenethyl ester and ethanol extract of propolis induce the complementary cytotoxic effect on triple-negative breast cancer cell lines.

    PubMed

    Rzepecka-Stojko, Anna; Kabała-Dzik, Agata; Moździerz, Aleksandra; Kubina, Robert; Wojtyczka, Robert D; Stojko, Rafał; Dziedzic, Arkadiusz; Jastrzębska-Stojko, Żaneta; Jurzak, Magdalena; Buszman, Ewa; Stojko, Jerzy

    2015-05-20

    Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells' susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP) and its derivative caffeic acid phenethyl ester (CAPE) towards two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH) assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL-1 for MDA-MB-23 cells and 33.68 µg∙mL-1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

  5. Monitoring of phenytoin in human breast milk, maternal plasma and cord blood plasma by solid-phase extraction and liquid chromatography.

    PubMed

    Shimoyama, R; Ohkubo, T; Sugawara, K; Ogasawara, T; Ozaki, T; Kagiya, A; Saito, Y

    1998-08-01

    A rapid liquid chromatographic method for the quantitation of phenytoin in human breast milk, maternal plasma and cord blood plasma was developed using a Develosil C85 micron reverse phase column and a potassium dihydrogen phosphate buffer/acetonitrile mobile phase. Phenytoin and mephenytoin as an internal standard were detected by ultraviolet absorbance at 240 nm. The sample preparation method involves a rapid and simple procedure based on solid-phase extraction using a C18-bonded phase. Phenytoin could be determined in the concentration range of 0.05-3 micrograms ml-1. The recovery of phenytoin added to human breast milk and plasma were 91.6-94.7 and 91.6-96.0%, respectively, with coefficient of variation less than 4.2 and 8.7%. The method has been used for drug level monitoring in the human breast milk, maternal plasma and cord blood plasma samples that were taken from patients treated with phenytoin. The average ratio between the breast milk concentrations versus the plasma concentration was 0.28 +/- 0.1, with a rather poor correlation (r = 0.3033).

  6. Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack) Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231

    PubMed Central

    Marvibaigi, Mohsen; Amini, Neda; Supriyanto, Eko; Abdul Majid, Fadzilah Adibah; Kumar Jaganathan, Saravana; Jamil, Shajarahtunnur; Hamzehalipour Almaki, Javad; Nasiri, Rozita

    2016-01-01

    Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated. PMID:27410459

  7. Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack) Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231.

    PubMed

    Marvibaigi, Mohsen; Amini, Neda; Supriyanto, Eko; Abdul Majid, Fadzilah Adibah; Kumar Jaganathan, Saravana; Jamil, Shajarahtunnur; Hamzehalipour Almaki, Javad; Nasiri, Rozita

    2016-01-01

    Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated.

  8. Mitochondrial Apoptosis Induced by Chamaemelum Nobile Extract in Breast Cancer Cells

    PubMed Central

    Mostafapour Kandelous, Hirsa; Salimi, Misha; Khori, Vahid; Rastkari, Noushin; Amanzadeh, Amir; Salimi, Mona

    2016-01-01

    Chamaemelum nobile (Asteraceae) commonly known as 'Roman chamomile' is a medicinal plant used for numerous diseases in traditional medicine, although its anticancer activity is unknown. The present study was carried out to investigate the anticancer as well as apoptotic activity of ethyl acetate fraction of C. nobile on different cancerous cell lines. The cells were treated with varying concentrations (0.001- 0.25 mg/mL) of this fraction for 24, 48 and 72 h. Apoptosis induced in MCF-7 cells following treatment with ethyl acetate fraction was measured using Annexin V/PI, flowcytometry and western blotting analysis. The results showed that C. nobile ethyl acetate fraction revealed relatively high antiproliferative activity on MCF-7 cells; however, it caused minimal growth inhibitory response in normal cells. The involvement of apoptosis as a major cause of the fraction-induced cell death was confirmed by annexin-V/PI assay. In addition, ethyl acetate fraction triggered the mitochondrial apoptotic pathway by decreasing the Bcl-2 as well as increasing of Bax protein expressions and subsequently increasing Bax/Bcl-2 ratio. Furthermore, decreased proliferation of MCF-7 cells in the presence of the fraction was associated with G2/M phase cell cycle arrest. These findings confirm that ethyl acetate fraction of C.nobile may contain a diversity of phytochemicals which suppress the proliferation of MCF-7 cells by inducing apoptosis. PMID:28228817

  9. Mitochondrial Apoptosis Induced by Chamaemelum Nobile Extract in Breast Cancer Cells.

    PubMed

    Mostafapour Kandelous, Hirsa; Salimi, Misha; Khori, Vahid; Rastkari, Noushin; Amanzadeh, Amir; Salimi, Mona

    2016-01-01

    Chamaemelum nobile (Asteraceae) commonly known as 'Roman chamomile' is a medicinal plant used for numerous diseases in traditional medicine, although its anticancer activity is unknown. The present study was carried out to investigate the anticancer as well as apoptotic activity of ethyl acetate fraction of C. nobile on different cancerous cell lines. The cells were treated with varying concentrations (0.001- 0.25 mg/mL) of this fraction for 24, 48 and 72 h. Apoptosis induced in MCF-7 cells following treatment with ethyl acetate fraction was measured using Annexin V/PI, flowcytometry and western blotting analysis. The results showed that C. nobile ethyl acetate fraction revealed relatively high antiproliferative activity on MCF-7 cells; however, it caused minimal growth inhibitory response in normal cells. The involvement of apoptosis as a major cause of the fraction-induced cell death was confirmed by annexin-V/PI assay. In addition, ethyl acetate fraction triggered the mitochondrial apoptotic pathway by decreasing the Bcl-2 as well as increasing of Bax protein expressions and subsequently increasing Bax/Bcl-2 ratio. Furthermore, decreased proliferation of MCF-7 cells in the presence of the fraction was associated with G2/M phase cell cycle arrest. These findings confirm that ethyl acetate fraction of C.nobile may contain a diversity of phytochemicals which suppress the proliferation of MCF-7 cells by inducing apoptosis.

  10. Autophagy Induced by Areca Nut Extract Contributes to Decreasing Cisplatin Toxicity in Oral Squamous Cell Carcinoma Cells: Roles of Reactive Oxygen Species/AMPK Signaling

    PubMed Central

    Xu, Zhi; Huang, Chun-Ming; Shao, Zhe; Zhao, Xiao-Ping; Wang, Meng; Yan, Ting-Lin; Zhou, Xiao-Cheng; Jiang, Er-Hui; Liu, Ke; Shang, Zheng-Jun

    2017-01-01

    Chewing areca nut is closely associated with oral squamous cell carcinoma (OSCC). The current study aimed to investigate potential associations between areca nut extract (ANE) and cisplatin toxicity in OSCC cells. OSCC cells (Cal-27 and Scc-9) viability and apoptosis were analyzed after treatment with ANE and/or cisplatin. The expressions of proteins associated with autophagy and the AMP-activated protein kinase (AMPK) signaling network were evaluated. We revealed that advanced OSCC patients with areca nut chewing habits presented higher LC3 expression and poorer prognosis. Reactive oxygen species (ROS)-mediated autophagy was induced after pro-longed treatment of ANE (six days, 3 μg). Cisplatin toxicity (IC50, 48 h) was decreased in OSCC cells after ANE treatment (six days, 3 μg). Cisplatin toxicity could be enhanced by reversed autophagy by pretreatment of 3-methyladenine (3-MA), N-acetyl-l-cysteine (NAC), or Compound C. Cleaved-Poly-(ADP-ribose) polymerase (cl-PARP) and cleaved-caspase 3 (cl-caspase 3) were downregulated in ANE-treated OSCC cells in the presence of cisplatin, which was also reversed by NAC and Compound C. Collectively, ANE could decrease cisplatin toxicity of OSCC by inducing autophagy, which involves the ROS and AMPK/mTOR signaling pathway. PMID:28257034

  11. Adlay seed extract (Coix lachryma-jobi L.) decreased adipocyte differentiation and increased glucose uptake in 3T3-L1 cells.

    PubMed

    Ha, Do Thi; Nam Trung, Trinh; Bich Thu, Nguyen; Van On, Tran; Hai Nam, Nguyen; Van Men, Chu; Thi Phuong, Tran; Bae, KiHwan

    2010-12-01

    The aim of the present study was to investigate effects of the ethyl acetate fraction of an ethanol extract of Coix lachryma-jobi (ECLJ) on glucose uptake and adipocyte differentiation in 3T3-L1 cells. ECLJ phosphorylated AMP-activated protein kinase (AMPK) and its downstream substrate acetyl-coenzymeA carboxylase in 3T3-L1 cells in a time- and dose-dependent manner. Moreover, we discovered that compound C inhibits ECLJ-stimulated ACC phosphorylation. In addition, ECLJ exhibited a dose-dependent stimulation of glucose uptake in 3T3-L1 cells, and this increase was obviously attenuated by compound C. ECLJ also caused a decrease in the expression levels of adipogenesis factors such as fatty acid synthase, sterol-regulatory-element-binding protein-1c, peroxisome proliferator-activated receptor γ, and CAATT/enhancer binding protein α in a dose-dependent manner. Differentiation was examined by Oil red O staining activity after ECLJ treatment for 6 days. ECLJ decreased mean droplet size. These results suggest a possible role for AMPK in the process of adipose differentiation and that ECLJ targeted for adipocyte functions could be effective in improving the symptoms of metabolic syndrome.

  12. Vaginal Testosterone Cream vs Estradiol Vaginal Ring for Vaginal Dryness or Decreased Libido in Women Receiving Aromatase Inhibitors for Early-Stage Breast Cancer: A Randomized Clinical Trial.

    PubMed

    Melisko, Michelle E; Goldman, Mindy E; Hwang, Jimmy; De Luca, Amy; Fang, Sally; Esserman, Laura J; Chien, Amy J; Park, John W; Rugo, Hope S

    2017-03-01

    Aromatase inhibitors (AI) are associated with significant urogenital atrophy, affecting quality of life and drug compliance. To evaluate safety of intravaginal testosterone cream (IVT) or an estradiol-releasing vaginal ring (7.5 μg/d) in patients with early-stage breast cancer (BC) receiving an AI. Intervention was considered unsafe if more than 25% of patients had persistent elevation in estradiol (E2), defined as E2 greater than 10 pg/mL (to convert to pmol/L, multiply by 3.671) and at least 10 pg/mL above baseline after treatment initiation on 2 consecutive tests at least 2 weeks apart. Postmenopausal (PM) women with hormone receptor (HR)-positive stage I to III BC taking AIs with self-reported vaginal dryness, dyspareunia, or decreased libido were randomized to 12 weeks of IVT or an estradiol vaginal ring. Estradiol was measured at baseline and weeks 4 and 12 using a commercially available liquid chromatography and tandem mass spectrometry assay; follicle-stimulating hormone levels were measured at baseline and week 4. Gynecologic examinations and sexual quality-of-life questionnaires were completed at baseline and week 12. This randomized noncomparative design allowed safety evaluation of 2 interventions concurrently in the same population of patients, reducing the possibility of E2 assay variability over time and between the 2 interventions. The primary objective of this trial was to evaluate safety of IVT or an estradiol vaginal ring in patients with early-stage BC receiving an AI; secondary objectives included evaluation of adverse events, changes in sexual quality of life using the Cancer Rehabilitation Evaluation System sexuality subscales, changes in vaginal atrophy using a validated 4-point scale, and comparison of E2 levels. Overall, 76 women signed consent (mean [range] age, 56 [37-78] years), 75 started treatment, and 69 completed 12 weeks of treatment. Mean (range) baseline E2 was 20 (<2 to 127) pg/mL. At baseline, E2 was above the postmenopausal

  13. Genotyping Concordance in DNA Extracted from Formalin-Fixed Paraffin Embedded (FFPE) Breast Tumor and Whole Blood for Pharmacogenetic Analyses

    PubMed Central

    Hertz, Daniel L; Kidwell, Kelley M; Thibert, Jacklyn N; Gersch, Christina; Regan, Meredith M; Skaar, Todd C; Henry, N. Lynn; Hayes, Daniel F; Van Poznak, Catherine H; Rae, James M

    2015-01-01

    Background Cancer pharmacogenetic studies have used archival tumor samples as a DNA source when germline DNA was unavailable. Genotyping DNA extracted from formalin-fixed paraffin embedded tumors (FFPE-T) may be inaccurate compared to that from normal leukocytes due to FFPE storage, tumor genetic aberrations, and/or insufficient DNA extraction. Our objective was to assess the extent and source of genotyping inaccuracy from FFPE-T DNA and demonstrate analytical validity of FFPE-T genotyping of candidate single nucleotide polymorphisms (SNPs) for pharmacogenetic analyses. Methods SNPs relevant to cancer pharmacogenetics were genotyped by Sequenom MassARRAYs in DNA harvested from matched FFPE-T, FFPE non-cancerous lymph node (FFPE-LN), and whole blood leukocyte samples obtained from early stage breast cancer patients. No-call and discordant call rates were calculated for each tissue type (FFPE-T, FFPE-LN, blood) and each SNP. Analytical validity was defined as all SNPs with <5% discordance between FFPE-T and blood or <10% discordance plus no-calls. Results Matched samples from 114 patients were genotyped for 247 SNPs. No-call rate in FFPE-T was greater than FFPE-LN and blood (4.3% vs. 3.0% vs. 0.5%, all p<0.001). The overall rate of genotype discordance between FFPE-T and leukocytes was very low, but greater than the discordance between FFPE-LN and leukocytes (1.1% vs. 0.3%, p<0.001). Samples with heterozygous genotypes were more likely to be no- or discordantly-called in FFPE-T and FFPE-LN (p<0.001). Analytical validity of FFPE-T genotyping was demonstrated for 218 (88%) SNPs. Conclusions No- and discordant-call rates were below concerning thresholds, confirming that most SNPs can be accurately genotyped from FFPE-T on the Sequenom platform. FFPE-T is a viable DNA source for prospective-retrospective pharmacogenetic analyses of clinical trial cohorts when germline DNA is not available. PMID:26276228

  14. [Extraction and identification of exosomes from drug-resistant breast cancer cells and their potential role in cell-to-cell drug-resistance transfer].

    PubMed

    Xu, Jinjin; Li, Wenjing; Zhong, Shanliang; Li, Xiujuan; Chen, Zhiyuan; Hu, Qing; Tang, Jinhai; Zhao, Jianhua

    2014-03-01

    To explore whether docetaxel-resistant cells (MCF-7/Doc) and doxorubicin-resistant cells (MCF-7/ADM) can secrete Exosomes and their potential role in cell-cell drug-resistance transfer. Exosomes were extracted from the cell culture supernatants of MCF-7/Doc and MCF-7/ADM cells by fractionation ultracentrifugation, and were identified by transmission electron microscopy and Western blot analysis. GFP-MCF-7/S, a breast cancer parental sensitive cell line stably expressing green fluorescent protein (GFP), was constructed by recombinant lentiviral vector with GFP. Then the resistance experiment of cells and the experiment of resistance transfer by exosomes were designed to observe the phenomenon of cell-to-cell drug-resistance transfer. Similar to the breast cancer parental sensitive cells (MCF-7/S), the breast cancer resistant sublines could secrete exosomes, which exhibited round or elliptic shape ranging from 30 to 100 nm in diameter with intact membrane, and only expressed the protein marker of exosomes, Tsg101, did not express the endoplasmic reticulum marker calnexin. After MCF-7/S, MCF-7/DOC and MCF-7/ADM cells we cocultured with GFP-MCF-7/S cells for 72 h, there were no significant differences in the expression of fluorescence-labeled cells among the four groups. When treated by the drug ADM or DOC for 24 hours, the MCF-7/DOC+GFP-MCF-7/S group was in favor of a significant higher survival rate of fluorescence-labeled cells compared with the MCF-7/S+GFP-MCF-7/S group (65.5% vs. 25.5%, P < 0.001), and so did the MCF-7/ADM+GFP-MCF-7/S group (53.6% vs. 25.4%, P < 0.001). The exosomes extracted from MCF-7/S, MCF-7/DOC and MCF-7/ADM cells were cultured with the GFP-MCF-7/S cells for 48 h. Among these groups, no significant differences in the expression of fluorescence-labeled cells were found. After treated by the drug ADM or DOC for 24 hours, the exosomes extracted from MCF-7/DOC+GFP-MCF-7/S group was associated with a significant higher survival rate of

  15. High miR-26a and low CDC2 levels associate with decreased EZH2 expression and with favorable outcome on tamoxifen in metastatic breast cancer.

    PubMed

    Jansen, M P H M; Reijm, E A; Sieuwerts, A M; Ruigrok-Ritstier, K; Look, M P; Rodríguez-González, F G; Heine, A A J; Martens, J W; Sleijfer, S; Foekens, J A; Berns, E M J J

    2012-06-01

    For patients with metastatic breast cancer, we previously described that increased EZH2 expression levels were associated with an adverse outcome to tamoxifen therapy. Main objective of the present study is to investigate miR-26a and miR-101 levels, which both target EZH2, for their association with molecular pathways and with efficacy of tamoxifen as first-line monotherapy for metastatic breast cancer. Expression levels were measured using quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) in primary breast cancer specimens of 235 estrogen receptor-α (ER)-positive patients. Pathway analysis was performed on microarray data available for 65 of these tumors. Logistic regression and Cox uni- and multivariate analysis were performed to relate expression levels with clinical benefit and time to progression (TTP). Increasing levels of miR-26a were significantly (P < 0.005) associated with both clinical benefit and prolonged TTP, whereas miR-101 was not. Cell cycle regulation and CCNE1 and CDC2 were the only significant overlapping pathway and genes differentially expressed between tumors with high and low levels of miR-26a and EZH2, respectively. In addition, increasing mRNA levels of CCNE1 (P < 0.05) and CDC2 (P < 0.001) were related to poor outcome. Multivariate analysis revealed miR-26a and CDC2 as an optimal set of markers associated with outcome on tamoxifen therapy, independently of traditional predictive factors. To summarize, only miR-26a levels are related with treatment outcome. Cell cycle regulation is the only overlapping pathway linked to miR-26a and EZH2 levels. Low mRNA levels of EZH2, CCNE1, and CDC2, and high levels of miR-26a are associated with favorable outcome on tamoxifen.

  16. Antilisterial activity and consumer acceptance of irradiated chicken breast meat vacuum-infused with grape seed and green tea extracts and tartaric acid.

    PubMed

    Over, K F; Hettiarachchy, N S; Perumalla, A V S; Johnson, M G; Meullenet, J-F; Dickson, J S; Holtzbauer, M J; Niebuhr, S E; Davis, B

    2010-09-01

    Contamination of poultry with pathogenic bacteria contributes to human foodborne disease, causes damage to industry brand names, and has a significant economic impact on the food industry in the form of both damage to industry brand names and losses associated with recalls. Irradiation is a safe and effective means of decontaminating poultry products, but the maximum dose strengths allowed negatively impact poultry sensory quality characteristics. The 1st objective of this study was to investigate the potential interactive inhibitory effects of natural antimicrobials as components of a vacuum-marination in addition to various dose levels of irradiation. Tartaric acid (TA) at 2 levels and grape seed (GS) and green tea (GT) extracts were combined, vacuum-infused into chicken breast fillets, and irradiated at 1, 2, and 3 kGy by electron beam irradiation. The 2nd objective was to use a consumer test group to evaluate TA and plant extract infusion into chicken breast fillets with and without irradiation at 2 kGy on overall impression, flavor, texture, appearance, and tenderness. The results showed that samples vacuum-infused with TA at 37.5 and 75.0 mM and irradiated at 1 kGy significantly reduced Listeria monocytogenes (L.m.) levels by 2 and 3 log CFU/g compared to the control after 12 d of refrigerated storage. Vacuum-infusion of TA at 37.5 and 75.0 mM at 2 and 3 kGy irradiation, reduced L.m. to near nondetectable levels. The addition of TA and GS and GT to chicken breast fillets with and without irradiation did not significantly impact consumer preference, tenderness, appearance, or flavor. The addition of tartaric acid and natural plant extracts to chicken marinades could contribute to the prevention of L.m. contamination.

  17. Ultrasonographic Observation of the Breast in Early Postmenopausal Women during Therapy with Cimicifuga Foetida Extract and Sequential Therapy with Estrogen and Progestin

    PubMed Central

    Gaowa, Sharen; Sun, Ai-Jun; Jiang, Ying; He, Fa-Wei; Zheng, Ting-Ping; Wang, Ya-Ping

    2015-01-01

    Background: It is now recognized that Cimicifuga foetida (C. foetida) extract is effective in alleviating menopausal symptoms. But the durations reported were usually short. The aim of this study was to investigate the effects of C. foetida extract therapy and different estrogen and progesterone sequential therapies, on the breasts of early postmenopausal women. Methods: This was a prospective randomized trial. Ninety-six early menopausal women were recruited and randomly assigned into three groups treated with different therapies for 2 years. Patients were given C. foetida extract in Group A, estradiol valerate and medroxyprogesterone acetate in Group B, and estradiol valerate and progesterone in Group C. Ultrasonography was used to monitor changes in breast during treatment. Results: In comparing breast glandular section thickness before and after 1 and 2 years of treatment, no significant difference was observed in Group A (11.97 ± 2.84 mm vs. 12.09 ± 2.58 mm and 12.61 ± 3.73 mm, P > 0.05); in Group B glandular section thickness had increased significantly (10.98 ± 2.34 mm vs. 11.84 ± 2.72 mm and 11.90 ± 3.33 mm, P < 0.05) after treatment, the same as Group C (11.56 ± 3.03 mm vs. 12.5 ± 3.57 mm and 12.22 ± 4.39 mm P < 0.05). In comparing breast duct width before and after 1 and 2 years of treatment, no significant difference was seen in Group A (1.07 ± 0.19 mm vs. 1.02 ± 0.18 mm and 0.98 ± 0.21 mm, P > 0.05); in Group B the duct width had a downward trend after treatment (0.99 ± 0.14 mm vs. 0.96 ± 0.22 mm and 0.90 ± 0.18 mm, P < 0.05), the same as Group C (1.07 ± 0.20 mm vs. 1.02 ± 0.17 mm and 0.91 ± 0.19 mm, P < 0.05). The nodules detected before treatment had disappeared after 1-year of treatment or exhibited no distinct changes in the three groups. However, new breast nodules had appeared after 2 years of treatment: There was one case in Group A, two cases in Group B and four cases in Group C, with breast hyperplasia after the molybdenum

  18. The total flavonoids extracted from Xiaobuxin-Tang up-regulate the decreased hippocampal neurogenesis and neurotrophic molecules expression in chronically stressed rats.

    PubMed

    An, Lei; Zhang, You-Zhi; Yu, Neng-Jiang; Liu, Xin-Min; Zhao, Nan; Yuan, Li; Chen, Hong-Xia; Li, Yun-Feng

    2008-08-01

    Xiaobuxin-Tang (XBXT), a traditional Chinese herbal decoction, has been used for the treatment of depressive disorders for centuries in China. Our previous studies have demonstrated that the total flavonoids (XBXT-2) isolated from the extract of XBXT reversed behavioral alterations and serotonergic dysfunctions in chronically stressed rats. Recently, accumulating studies have suggested the behavioral effects of chronic antidepressants treatment might be mediated by the stimulation of hippocampal neurogenesis. In present study, we explored the effect of XBXT-2 on hippocampal neurogenesis and neurotrophic signal pathway in chronically stressed rats. Our immunohistochemistry results showed that concomitant administration of XBXT-2 (25, 50 mg/kg, p.o., 28 days, the effective doses for behavioral responses) significantly increased hippocampal neurogenesis in chronically stressed rats. Four weeks after BrdU injection, result in double immunofluorescence labeling showed that some of the newly generated cells in hippocampus co-expressed with NSE or GFAP, markers for neurons or astrocytes, respectively. Furthermore, XBXT-2 treatment reserved stress-induced decrease of hippocampal BDNF and pCREB (Ser133) expression, two important factors which were closely related to hippocampal neurogenesis. As a positive control drug, imipramine (10 mg/kg, p.o.) exerted same effects. In conclusion, the increase of neurogenesis, as well as expression of BDNF and pCREB in hippocampus may be one of the molecular and cellular mechanisms underlying the antidepressant action of XBXT-2.

  19. A point mutation in the putative TATA box, detected in nondiseased individuals and patients with hereditary breast cancer, decreases promoter activity of the 17{beta}-hydroxysteroid dehydrogenase type 1 gene 2 (EDH17B2) in vitro

    SciTech Connect

    Peltoketo, H.; Piao, Y.; Isomaa, V.

    1994-09-01

    EDH17B2, the gene encoding 17{beta}-hydroxysteroid dehydrogenase type 1, has been suggested as a candidate for the familial breast cancer gene, BRCA1, located on 17q12-q21. We analyzed the promoter region of EDH17B2 in DNA from 20 control individuals and 40 patients with familial breast cancer. Two frequent (designated vI and vIII) and two rare (vII and vIV) nucleotide variations were present in both the breast cancer patients and the controls, except the alteration vII, which was found only in one patient. Although the data do not support the identification of EDH17B2 as the BRCA1 gene, it is of interest that point mutation vIV (A {yields} C) was located in the putative TATA box of the EDH17B2 gene. Reporter gene analysis showed that the mutation vIV decreases EDH17B2 promoter activity by an average of 45% in in vitro assays, suggesting that nucleotide A at position -27 is significant for efficient transcription. 12 refs., 2 figs., 1 tab.

  20. Artemisinin selectively decreases functional levels of estrogen receptor-alpha and ablates estrogen-induced proliferation in human breast cancer cells.

    PubMed

    Sundar, Shyam N; Marconett, Crystal N; Doan, Victor B; Willoughby, Jamin A; Firestone, Gary L

    2008-12-01

    MCF7 cells are an estrogen-responsive human breast cancer cell line that expresses both estrogen receptor (ER) alpha and ERbeta. Treatment of MCF7 cells with artemisinin, an antimalarial phytochemical from the sweet wormwood plant, effectively blocked estrogen-stimulated cell cycle progression induced by either 17beta-estradiol (E(2)), an agonist for both ERs, or by propyl pyrazole triol (PPT), a selective ERalpha agonist. Artemisinin strongly downregulated ERalpha protein and transcripts without altering expression or activity of ERbeta. Transfection of MCF7 cells with ERalpha promoter-linked luciferase reporter plasmids revealed that the artemisinin downregulation of ERalpha promoter activity accounted for the loss of ERalpha expression. Artemisinin treatment ablated the estrogenic induction of endogenous progesterone receptor (PR) transcripts by either E(2) or PPT and inhibited the estrogenic stimulation of a luciferase reporter plasmid driven by consensus estrogen response elements (EREs). Chromatin immunoprecipitation assays revealed that artemisinin significantly downregulated the level of endogeneous ERalpha bound to the PR promoter, whereas the level of bound endogeneous ERbeta was not altered. Treatment of MCF7 cells with artemisinin and the pure antiestrogen fulvestrant resulted in a cooperative reduction of ERalpha protein levels and enhanced G(1) cell cycle arrest compared with the effects of either compound alone. Our results show that artemisinin switches proliferative human breast cancer cells from expressing a high ERalpha:ERbeta ratio to a condition in which ERbeta predominates, which parallels the physiological state linked to antiproliferative events in normal mammary epithelium.

  1. Momordica cochinchinensis seed extracts suppress migration and invasion of human breast cancer ZR-75-30 cells via down-regulating MMP-2 and MMP-9.

    PubMed

    Zheng, Lei; Zhang, Yan-Min; Zhan, Ying-Zhuan; Liu, Chang-Xiao

    2014-01-01

    Metastases and invasion are the main reasons for oncotherapy failure. Momordica cochinchinensis (Mu Bie Zi in Chinese) had been used for a variety of purposes, and shown anti-cancer action. In this article, we focused on effects on regulation of breast cancer cell ZR-75-30 metastases and invasion by extracts of Momordica cochinchinensis seeds (ESMCs). Effect of ESMCs on ZR-75-30 human breast cancer cells proliferation were evaluated by MTT assay and on invasion and migration by wound-healing and matrigel invasion chamber assays. Expression and protease activity of two matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were analyzed by Western blotting and gelatin zymography, respectively. ESMC revealed strong growth inhibitory effects on ZR-75-30 cells, and effectively inhibited ZR-75-30 cell invasion in a dose-dependent manner. Western blot and gelatin zymography analysis showed that ESMC significantly inhibited the expression and secretion of MMP-2 and MMP-9 in ZR-75-30 cells. ESMC has the potential to suppress the migration and invasion of ZR-75-30 cancer cells, and it might prove to of interest in the development of novel inhibitors for breast cancer.

  2. Differential Control of Growth, Apoptotic Activity, and Gene Expression in Human Breast Cancer Cells by Extracts Derived from Medicinal Herbs Zingiber officinale

    PubMed Central

    Elkady, Ayman I.; Abuzinadah, Osama A.; Baeshen, Nabih A.; Rahmy, Tarek R.

    2012-01-01

    The present study aimed to examine the antiproliferative potentiality of an extract derived from the medicinal plant ginger (Zingiber officinale) on growth of breast cancer cells. Ginger treatment suppressed the proliferation and colony formation in breast cancer cell lines, MCF-7 and MDA-MB-231. Meanwhile, it did not significantly affect viability of nontumorigenic normal mammary epithelial cell line (MCF-10A). Treatment of MCF-7 and MDA-MB-231 with ginger resulted in sequences of events marked by apoptosis, accompanied by loss of cell viability, chromatin condensation, DNA fragmentation, activation of caspase 3, and cleavage of poly(ADP-ribose) polymerase. At the molecular level, the apoptotic cell death mediated by ginger could be attributed in part to upregulation of Bax and downregulation of Bcl-2 proteins. Ginger treatment downregulated expression of prosurvival genes, such as NF-κB, Bcl-X, Mcl-1, and Survivin, and cell cycle-regulating proteins, including cyclin D1 and cyclin-dependent kinase-4 (CDK-4). On the other hand, it increased expression of CDK inhibitor, p21. It also inhibited the expression of the two prominent molecular targets of cancer, c-Myc and the human telomerase reverse transcriptase (hTERT). These findings suggested that the ginger may be a promising candidate for the treatment of breast carcinomas. PMID:22969274

  3. Apoptotic effects of Physalis minima L. chloroform extract in human breast carcinoma T-47D cells mediated by c-myc-, p53-, and caspase-3-dependent pathways.

    PubMed

    Ooi, Kheng Leong; Tengku Muhammad, Tengku Sifzizul; Lim, Chui Hun; Sulaiman, Shaida Fariza

    2010-03-01

    The chloroform extract of Physalis minima produced a significant growth inhibition against human T-47D breast carcinoma cells as compared with other extracts with an EC(50) value of 3.8 microg/mL. An analysis of cell death mechanisms indicated that the extract elicited an apoptotic cell death. mRNA expression analysis revealed the coregulation of apoptotic genes, that is, c-myc , p53, and caspase-3. The c-myc was significantly induced by the chloroform extract at the earlier phase of treatment, followed by p53 and caspase-3. Biochemical assay and ultrastructural observation displayed typical apoptotic features in the treated cells, including DNA fragmentation, blebbing and convolution of cell membrane, clumping and margination of chromatin, and production of membrane-bound apoptotic bodies. The presence of different stages of apoptotic cell death and phosphatidylserine externalization were further reconfirmed by annexin V and propidium iodide staining. Thus, the results from this study strongly suggest that the chloroform extract of P. minima induced apoptotic cell death via p53-, caspase-3-, and c-myc-dependent pathways.

  4. Maintaining Breast Cancer Specimen Integrity and Individual or Simultaneous Extraction of Quality DNA, RNA, and Proteins from Allprotect-Stabilized and Nonstabilized Tissue Samples

    PubMed Central

    Carroll, Paul; Donatello, Simona; Connolly, Elizabeth; Griffin, Mairead; Dunne, Barbara; Burke, Louise; Flavin, Richard; Rizkalla, Hala; Ryan, Ciara; Hayes, Brian; D'Adhemar, Charles; Banville, Niamh; Faheem, Nazia; Muldoon, Cian; Gaffney, Eoin F.

    2011-01-01

    The Saint James's Hospital Biobank was established in 2008, to develop a high-quality breast tissue BioResource, as a part of the breast cancer clinical care pathway. The aims of this work were: (1) to ascertain the quality of RNA, DNA, and protein in biobanked carcinomas and normal breast tissues, (2) to assess the efficacy of AllPrep® (Qiagen) in isolating RNA, DNA, and protein simultaneously, (3) to compare AllPrep with RNEasy® and QIAamp® (both Qiagen), and (4) to examine the effectiveness of Allprotect® (Qiagen), a new tissue stabilization medium in preserving DNA, RNA, and proteins. One hundred eleven frozen samples of carcinoma and normal breast tissue were analyzed. Tumor and normal tissue morphology were confirmed by frozen sections. Tissue type, tissue treatment (Allprotect vs. no Allprotect), extraction kit, and nucleic acid quantification were analyzed by utilizing a 4 factorial design (SPSS PASW 18 Statistics Software®). QIAamp (DNA isolation), AllPrep (DNA, RNA, and Protein isolation), and RNeasy (RNA isolation) kits were assessed and compared. Mean DNA yield and A260/280 values using QIAamp were 33.2 ng/μL and 1.86, respectively, and using AllPrep were 23.2 ng/μL and 1.94. Mean RNA yield and RNA Integrity Number (RIN) values with RNeasy were 73.4 ng/μL and 8.16, respectively, and with AllPrep were 74.8 ng/μL and 7.92. Allprotect-treated tissues produced higher RIN values of borderline significance (P=0.055). No discernible loss of RNA stability was detected after 6 h incubation of stabilized or nonstabilized tissues at room temperature or 4°C or in 9 freeze-thaw cycles. Allprotect requires further detailed evaluation, but we consider AllPrep to be an excellent option for the simultaneous extraction of RNA, DNA, and protein from tumor and normal breast tissues. The essential presampling procedures that maintain the diagnostic integrity of pathology specimens do not appear to compromise the quality of molecular isolates. PMID

  5. Maintaining Breast Cancer Specimen Integrity and Individual or Simultaneous Extraction of Quality DNA, RNA, and Proteins from Allprotect-Stabilized and Nonstabilized Tissue Samples.

    PubMed

    Mee, Blanaid C; Carroll, Paul; Donatello, Simona; Connolly, Elizabeth; Griffin, Mairead; Dunne, Barbara; Burke, Louise; Flavin, Richard; Rizkalla, Hala; Ryan, Ciara; Hayes, Brian; D'Adhemar, Charles; Banville, Niamh; Faheem, Nazia; Muldoon, Cian; Gaffney, Eoin F

    2011-12-01

    The Saint James's Hospital Biobank was established in 2008, to develop a high-quality breast tissue BioResource, as a part of the breast cancer clinical care pathway. The aims of this work were: (1) to ascertain the quality of RNA, DNA, and protein in biobanked carcinomas and normal breast tissues, (2) to assess the efficacy of AllPrep(®) (Qiagen) in isolating RNA, DNA, and protein simultaneously, (3) to compare AllPrep with RNEasy(®) and QIAamp(®) (both Qiagen), and (4) to examine the effectiveness of Allprotect(®) (Qiagen), a new tissue stabilization medium in preserving DNA, RNA, and proteins. One hundred eleven frozen samples of carcinoma and normal breast tissue were analyzed. Tumor and normal tissue morphology were confirmed by frozen sections. Tissue type, tissue treatment (Allprotect vs. no Allprotect), extraction kit, and nucleic acid quantification were analyzed by utilizing a 4 factorial design (SPSS PASW 18 Statistics Software(®)). QIAamp (DNA isolation), AllPrep (DNA, RNA, and Protein isolation), and RNeasy (RNA isolation) kits were assessed and compared. Mean DNA yield and A(260/280) values using QIAamp were 33.2 ng/μL and 1.86, respectively, and using AllPrep were 23.2 ng/μL and 1.94. Mean RNA yield and RNA Integrity Number (RIN) values with RNeasy were 73.4 ng/μL and 8.16, respectively, and with AllPrep were 74.8 ng/μL and 7.92. Allprotect-treated tissues produced higher RIN values of borderline significance (P=0.055). No discernible loss of RNA stability was detected after 6 h incubation of stabilized or nonstabilized tissues at room temperature or 4°C or in 9 freeze-thaw cycles. Allprotect requires further detailed evaluation, but we consider AllPrep to be an excellent option for the simultaneous extraction of RNA, DNA, and protein from tumor and normal breast tissues. The essential presampling procedures that maintain the diagnostic integrity of pathology specimens do not appear to compromise the quality of molecular isolates.

  6. Control of Salmonella on fresh chicken breasts by κ-carrageenan/chitosan-based coatings containing allyl isothiocyanate or deodorized Oriental mustard extract plus EDTA.

    PubMed

    Olaimat, Amin N; Holley, Richard A

    2015-06-01

    Control of Salmonella in poultry is a public health concern as salmonellosis is one of the most common foodborne diseases worldwide. This study aimed to screen the ability of 5 Salmonella serovars to degrade the mustard glucosinolate, sinigrin (by bacterial myrosinase) in Mueller-Hinton broth at 25 °C for 21 d and to reduce Salmonella on fresh chicken breasts by developing an edible 0.2% (w/v) κ-carrageenan/2% (w/v) chitosan-based coating containing Oriental mustard extract, allyl isothiocyanate (AITC), EDTA or their combinations. Individual Salmonella serovars degraded 50.2%-55.9% of the sinigrin present in 21 d. κ-Carrageenan/chitosan-based coatings containing 250 mg Oriental mustard extract/g or 50 μl AITC/g reduced the numbers of Salmonella on chicken breasts 2.3 log10 CFU/g at 21 d at 4 °C. However, when either mustard extract or AITC was combined with 15 mg/g EDTA in κ-carrageenan/chitosan-based coatings, Salmonella numbers were reduced 2.3 log10 CFU/g at 5 d and 3.0 log10 CFU/g at 21 d. Moreover, these treatments reduced numbers of lactic acid bacteria and aerobic bacteria by 2.5-3.3 log10 CFU/g at 21 d. κ-Carrageenan/chitosan coatings containing either 50 μl AITC/g or 250 mg Oriental mustard extract/g plus 15 mg EDTA/g have the potential to reduce Salmonella on raw chicken.

  7. Cytotoxic Effect of Ethanol Extract of Microalga, Chaetoceros calcitrans, and Its Mechanisms in Inducing Apoptosis in Human Breast Cancer Cell Line

    PubMed Central

    Ebrahimi Nigjeh, Siyamak; Yusoff, Fatimah Md; Mohamed Alitheen, Noorjahan Banu; Rasoli, Mehdi; Keong, Yeap Swee; Omar, Abdul Rahman bin

    2013-01-01

    Marine microalgae have been prominently featured in cancer research. Here, we examined cytotoxic effect and apoptosis mechanism of crude ethanol extracts of an indigenous microalga, Chaetoceros calcitrans (UPMAAHU10) on human breast cell lines. MCF-7 was more sensitive than MCF-10A with IC50 value of 3.00 ± 0.65, whilst the IC50 value of Tamoxifen against MCF-7 was 12.00 ± 0.52 μg/mL after 24 hour incubation. Based on Annexin V/Propidium iodide and cell cycle flow cytometry analysis, it was found that inhibition of cell growth by EEC on MCF-7 cells was through the induction of apoptosis without cell cycle arrest. The apoptotic cells at subG0/G1 phase in treated MCF-7 cells at 48 and 72 hours showed 34 and 16 folds increased compared to extract treated MCF-10A cells which showed only 6 and 7 folds increased at the same time points, respectively. Based on GeXP study, EEC induced apoptosis on MCF-7 cells via modulation of CDK2, MDM2, p21Cip1, Cyclin A2, Bax and Bcl-2. The EEC treated MCF-7 cells also showed an increase in Bax/Bcl-2 ratio that in turn activated the caspase-dependent pathways by activating caspase 7. Thus, marine microalga, Chaetoceros calcitrans may be considered a good candidate to be developed as a new anti-breast cancer drug. PMID:23509778

  8. Anti-acne, anti-dandruff and anti-breast cancer efficacy of green synthesised silver nanoparticles using Coriandrum sativum leaf extract.

    PubMed

    Sathishkumar, Palanivel; Preethi, Johnson; Vijayan, Raji; Mohd Yusoff, Abdull Rahim; Ameen, Fuad; Suresh, Sadhasivam; Balagurunathan, Ramasamy; Palvannan, Thayumanavan

    2016-10-01

    In this present investigation, AgNPs were green synthesised using Coriandrum sativum leaf extract. The physicochemical properties of AgNPs were characterised using UV-visible spectrophotometer, field emission scanning microscopy/energy dispersive X-ray (FESEM/EDX), Fourier transformed infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and Brunauer-Emmett-Teller (BET) analysis. Further, in vitro anti-acne, anti-dandruff and anti-breast cancer efficacy of green synthesised AgNPs were assessed against Propionibacterium acnes MTCC 1951, Malassezia furfur MTCC 1374 and human breast adenocarcinoma (MCF-7) cell line, respectively. The flavonoids present in the plant extract were responsible for the AgNPs synthesis. The green synthesised nanoparticles size was found to be ≈37nm. The BET analysis result shows that the surface area of the synthesised AgNPs was found to be 33.72m(2)g(-1). The minimal inhibitory concentration (MIC) of AgNPs for acne causative agent P. acnes and dandruff causative agent M. furfur was found to be at 3.1 and 25μgmL(-1), respectively. The half maximal inhibitory concentration (IC50) value of the AgNPs for MCF-7 cells was calculated as 30.5μgmL(-1) and complete inhibition was observed at a concentration of 100μgmL(-1). Finally, our results proved that green synthesised AgNPs using C. sativum have great potential in biomedical applications such as anti-acne, anti-dandruff and anti-breast cancer treatment.

  9. HES1-mediated inhibition of Notch1 signaling by a Gemini vitamin D analog leads to decreased CD44(+)/CD24(-/low) tumor-initiating subpopulation in basal-like breast cancer.

    PubMed

    So, Jae Young; Wahler, Joseph; Das Gupta, Soumyasri; Salerno, David M; Maehr, Hubert; Uskokovic, Milan; Suh, Nanjoo

    2015-04-01

    Tumor-initiating cells (also known as cancer stem cells) are the subpopulation of cells shown to be responsible for tumor initiation, maintenance and recurrence. In breast cancer, CD44(+)/CD24(-/low) cells were identified as tumor-initiating cells. We previously reported that a Gemini vitamin D analog, 1,25-dihydroxy-20R-21(3-hydroxy-3-deuteromethyl-4,4,4-trideuterobutyl)-23-yne-26,27-hexafluoro-cholecalciferol (BXL0124), reduced CD44(+)/CD24(-/low) cells in MCF10DCIS basal-like breast cancer cells. Since Notch has been identified as one of the key signaling pathways involved in breast cancer stem cells, the effect of BXL0124 on the Notch signaling pathway was investigated in breast cancer. The CD44(+)/CD24(-/low) subpopulation of MCF10DCIS cells showed elevated Notch1 signaling and increased cell proliferation compared to the CD44(+)/CD24(high) subpopulation. Treatment with the Gemini vitamin D analog BXL0124 decreased the level of activated Notch1 receptor. In addition, mRNA and protein levels of the Notch ligands, Jagged-1, Jagged-2 and DLL1, were significantly reduced by treatment with BXL0124, which was followed by repression of c-Myc, a key downstream target of Notch signaling. Interestingly, HES1, a known downstream target of Notch signaling, was rapidly induced by treatment with BXL0124. The inhibitory effect of BXL0124 on Notch signaling was reversed by knockdown of HES1. Overexpression of HES1 inhibited Notch1 signaling and reduced the CD44(+)/CD24(-/low) subpopulation, confirming a role of HES1 in Notch1 signaling. In conclusion, the Gemini vitamin D analog, BXL0124, represses the tumor-initiating subpopulation by HES1-mediated inhibition of Notch1 signaling. The present study demonstrates BXL0124 as a potent inhibitor of Notch signaling to target tumor-initiating cells in basal-like breast cancer. This article is part of a Special Issue entitled "17th Vitamin D Workshop". Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Integrative analysis of genomics and proteomics data on clinical breast cancer tissue specimens extracted with acid guanidinium thiocyanate-phenol-chloroform.

    PubMed

    Braakman, René B H; Bezstarosti, Karel; Sieuwerts, Anieta M; de Weerd, Vanja; van Galen, Anne M; Stingl, Christoph; Luider, Theo M; Timmermans, Mieke A M; Smid, Marcel; Martens, John W M; Foekens, John A; Demmers, Jeroen A A; Umar, Arzu

    2015-03-06

    Acid guanidinium thiocyanate, phenol, and chloroform extraction (AGPC) is a commonly used procedure to extract RNA from fresh frozen tissues and cell lines. In addition, DNA and proteins can be recovered, which makes AGPC an attractive source for integrative analysis on tissues of which little material is available, such as clinical specimens. Despite this potential, AGPC has only scarcely been used for proteomic analysis, mainly due to difficulties in extracting proteins. We have used a quantitative mass spectrometry method to show that proteins can readily be recovered from AGPC extracted tissues with high recovery and repeatability, which allows this method to be used for global proteomic profiling. Protein expression data for a selected number of clinically relevant markers, of which transcript and protein levels are known to be correlated, were in agreement with genomic and transcriptomic data obtained from the same AGPC lysate. Furthermore, global proteomic profiling successfully discriminated breast tumor tissues according to their clinical subtype. Lastly, a reference gene set of differentially expressed transcripts was strongly enriched in the differentially abundant proteins in our cohort. AGPC lysates are therefore well suited for comparative protein and integrative analyses.

  11. Screening of antiproliferative effect of aqueous extracts of plant foods consumed in México on the breast cancer cell line MCF-7.

    PubMed

    García-Solís, Pablo; Yahia, Elhadi M; Morales-Tlalpan, Verónica; Díaz-Muñoz, Mauricio

    2009-01-01

    We evaluated the antiproliferative effect of aqueous extracts of 14 plant foods consumed in Mexico on the breast cancer cell line MCF-7. The plant foods used were avocado, black sapote, guava, mango, prickly pear cactus stems (called nopal in Mexico, cooked and raw), papaya, pineapple, four different cultivars of prickly pear fruit, grapes and tomato. β-Carotene, total phenolics and gallic acid contents and the antioxidant capacity, measured by the ferric reducing/antioxidant power and the 2,2-diphenyl-1,1-picrylhydrazyl radical scavenging assays, were analyzed in each aqueous extract. Only the papaya extract had a significant antiproliferative effect measured with the methylthiazolydiphenyl-tetrazolium bromide assay. We did not notice a relationship between the total phenolic content and the antioxidant capacity with antiproliferative effect. It is suggested that each extract of plant food has a unique combination of the quantity and quality of phytochemicals that could determine its biological activity. Besides, papaya represents a very interesting fruit to explore its antineoplastic activities.

  12. Antioxidant rich Morus alba leaf extract induces apoptosis in human colon and breast cancer cells by the downregulation of nitric oxide produced by inducible nitric oxide synthase.

    PubMed

    Deepa, Mundekkad; Sureshkumar, Thavamani; Satheeshkumar, Padikara Kutty; Priya, Sulochana

    2013-01-01

    Morus species had been used widely in the traditional medicines for various diseases. In this study we report the in vitro antiproliferative activity of the methanol extract of Morus alba. The extract is capable of inducing cytotoxicity in human colon cancer (HCT-15) cells (IC(50) = 13.8 μg/ml) and breast cancer (MCF-7) cells (IC(50) = 9.2 μg/ml), resulted in significant morphological changes of the cells, fragmentation of DNA, and caspase-3 activation- characteristics of apoptosis. It downregulated the amount of nitric oxide (NO) produced as a result of inducible nitric oxide (iNOS) activation. The HPLC analysis of the extract showed epicatechin (20%), myricetin (10%), quercetin hydrate (12%), luteolin (12%), and kaempferol (6%) as the major active components and ascorbic acid, gallic acid, pelargonidine, and p-coumaric acid as the minor components. To the best of our knowledge, this is the first report showing the downregulation of iNOS and induction of apoptosis by M. alba extract.

  13. Hydrophilic interaction liquid chromatography tandem mass spectrometry analysis of malonyl-coenzyme A in breast cancer cell cultures applying online solid-phase extraction.

    PubMed

    Schriewer, Alexander; Cadenas, Cristina; Hayen, Heiko

    2017-09-06

    Cofactors such as coenzyme A and its derivatives acetyl-coenzyme A and malonyl-coenzyme A are involved in many metabolic pathways. Due to trace level concentrations in biological samples and the high reactivity of cofactors, a fast, sensitive and selective method for quantification is mandatory. In this study, online solid-phase extraction was coupled successfully to hydrophilic interaction liquid chromatography with tandem mass spectrometry for analytes' isolation in complex matrix and quantification by external calibration. Online solid-phase extraction was carried out by application of a weak anion exchange column, whereas hydrophilic interaction liquid chromatography separation was performed on an amide modified stationary phase. Sample preparation of the extracts prior the analysis was reduced to a centrifugation and dilution step. Moreover, the applied online solid-phase extraction significantly reduced matrix effects and increased the signal-to-noise ratio. The limit of detection and the limit of quantification were in the lower nanomolar range. Finally, the applicability of this method was demonstrated on MCF-7