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Sample records for algae growth inhibition

  1. Use of Copper to Selectively Inhibit Brachionus calyciflorus (Predator) Growth in Chlorella kessleri (Prey) Mass Cultures for Algae Biodiesel Production.

    PubMed

    Pradeep, Vishnupriya; Van Ginkel, Steven W; Park, Sichoon; Igou, Thomas; Yi, Christine; Fu, Hao; Johnston, Rachel; Snell, Terry; Chen, Yongsheng

    2015-01-01

    A single Brachionus rotifer can consume thousands of algae cells per hour causing an algae pond to crash within days of infection. Thus, there is a great need to reduce rotifers in order for algal biofuel production to become reality. Copper can selectively inhibit rotifers in algae ponds, thereby protecting the algae crop. Differential toxicity tests were conducted to compare the copper sensitivity of a model rotifer-B. calyciflorus and an alga, C. kessleri. The rotifer LC50 was <0.1 ppm while the alga was not affected up to 5 ppm Cu(II). The low pH of the rotifer stomach may make it more sensitive to copper. However, when these cultures were combined, a copper concentration of 1.5 ppm was needed to inhibit the rotifer as the alga bound the copper, decreasing its bioavailability. Copper (X ppm) had no effect on downstream fatty acid methyl ester extraction. PMID:26404247

  2. Inhibition of mast cells by algae.

    PubMed

    Price, Joseph A; Sanny, Charles; Shevlin, Dennis

    2002-01-01

    There is a history of use of algae as foods and as food additives, or nutraceuticals. Although algae are a safe component of human foods and animal feeds, the effects of the algae other than as a source of protein are not clear. We examined the prevalence of an antiinflammatory activity in selected algae using, as an assay system, the inhibition of histamine release from mast cells. Methanolic extracts of eleven algae were examined for activity to inhibit the release of histamine from mast cells in vitro. This activity was found widely among the samples tested. The activities of these extracts were not uniformly stable in acid methanol. Selected extracts studied further did not separate with the use of size-exclusion filtration filters. LH-20 chromatography suggested at least two main elution areas of activity of the Chlorella extract. In summary, we saw wide phylogenetic dispersion of mast cell inhibition activity, suggesting that this antiinflammatory property is common in algae. This effect was apparently due to multiple activities within the algal extracts. PMID:12639395

  3. Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether, a marine algae derived bromophenol, inhibits the growth of Botrytis cinerea and interacts with DNA molecules.

    PubMed

    Liu, Ming; Wang, Genzhu; Xiao, Lin; Xu, Xuanli; Liu, Xiaohui; Xu, Pingxiang; Lin, Xiukun

    2014-07-01

    Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a bromophenol isolated from marine algae. Previous reports have shown that BDDE possesses cytotoxic and antibacterial activity. In the present study, we demonstrate that BDDE displays broad-spectrum antifungal activities, especially on Botrytis cinerea. BDDE inhibits the growth of B. cinerea cultured on a solid medium of potato dextrose agar (PDA) as well as on the potato dextrose broth (PDB) medium. Moreover, BDDE decreases the incidence of fruit decay and severity of strawberries infected with B. cinerea. Further studies have revealed that BDDE decreases the germination rate and inhibits the mycelial growth of B. cinerea. The inhibition mechanisms are related to the disruption of the cell membrane integrity in B. cinerea spores and newly formed germ tubes. This study also suggests that BDDE possibly interacts with DNA via intercalation and minor groove binding. The studies provide evidence that BDDE has potential application in the control of gray mold after fruit harvest and the compound could serve as a candidate or lead template for rational drug design and for the development of antifungal agents. PMID:24979270

  4. Estimation of alga growth stage and lipid content growth rate

    NASA Technical Reports Server (NTRS)

    Embaye, Tsegereda N. (Inventor); Trent, Jonathan D. (Inventor)

    2012-01-01

    Method and system for estimating a growth stage of an alga in an ambient fluid. Measured light beam absorption or reflection values through or from the alga and through an ambient fluid, in each of two or more wavelength sub-ranges, are compared with reference light beam absorption values for corresponding wavelength sub-ranges for in each alga growth stage to determine (1) which alga growth stage, if any, is more likely and (2) whether estimated lipid content of the alga is increasing or has peaked. Alga growth is preferably terminated when lipid content has approximately reached a maximum value.

  5. Modelling the effect of fluctuating herbicide concentrations on algae growth.

    PubMed

    Copin, Pierre-Jean; Coutu, Sylvain; Chèvre, Nathalie

    2015-03-01

    Herbicide concentrations fluctuate widely in watercourses after crop applications and rain events. The level of concentrations in pulses can exceed the water chronic quality criteria. In the present study, we proposed modelling the effects of successive pulse exposure on algae. The deterministic model proposed is based on two parameters: (i) the typical growth rate of the algae, obtained by monitoring growth rates of several successive batch cultures in growth media, characterizing both the growth of the control and during the recovery periods; (ii) the growth rate of the algae exposed to pulses, determined from a dose-response curve obtained with a standard toxicity test. We focused on the herbicide isoproturon and on the freshwater alga Scenedesmus vacuolatus, and we validated the model prediction based on effect measured during five sequential pulse exposures in laboratory. The comparison between the laboratory and the modelled effects illustrated that the results yielded were consistent, making the model suitable for effect prediction of the herbicide photosystem II inhibitor isoproturon on the alga S. vacuolatus. More generally, modelling showed that both pulse duration and level of concentration play a crucial role. The application of the model to a real case demonstrated that both the highest peaks and the low peaks with a long duration affect principally the cell density inhibition of the alga S. vacuolatus. It is therefore essential to detect these characteristic pulses when monitoring of herbicide concentrations are conducted in rivers. PMID:25499055

  6. Formation of algae growth constitutive relations for improved algae modeling.

    SciTech Connect

    Gharagozloo, Patricia E.; Drewry, Jessica L.

    2013-01-01

    This SAND report summarizes research conducted as a part of a two year Laboratory Directed Research and Development (LDRD) project to improve our abilities to model algal cultivation. Algae-based biofuels have generated much excitement due to their potentially large oil yield from relatively small land use and without interfering with the food or water supply. Algae mitigate atmospheric CO2 through metabolism. Efficient production of algal biofuels could reduce dependence on foreign oil by providing a domestic renewable energy source. Important factors controlling algal productivity include temperature, nutrient concentrations, salinity, pH, and the light-to-biomass conversion rate. Computational models allow for inexpensive predictions of algae growth kinetics in these non-ideal conditions for various bioreactor sizes and geometries without the need for multiple expensive measurement setups. However, these models need to be calibrated for each algal strain. In this work, we conduct a parametric study of key marine algae strains and apply the findings to a computational model.

  7. Effects of TiO2 nanoparticles on ROS production and growth inhibition using freshwater green algae pre-exposed to UV irradiation.

    PubMed

    Fu, Ling; Hamzeh, Mahsa; Dodard, Sabine; Zhao, Yuan H; Sunahara, Geoffrey I

    2015-05-01

    This study investigated the possibility that titanium dioxide nanoparticles (nano-TiO2) toxicity in Pseudokirchneriella subcapitata involves reactive oxygen species (ROS) production, using the dichlorodihydrofluorescein (DCF) assay. Algae were exposed to nano-TiO2 under laboratory fluorescent lamps supplemented with UV irradiation for 3h, with or without a UV filter. Results showed that nano-TiO2 increased ROS production in UV-exposed cells, with or without a UV filter (LOEC values were 250 and 10mg/L, respectively). Sublethal effects of nano-TiO2 on UV pre-exposed algae were also examined. Toxicity studies indicated that exposure to nano-TiO2 agglomerates decreased algal growth following 3h pre-exposure to UV, with or without a UV filter (EC50s were 8.7 and 6.3mg/L, respectively). The present study suggests that the growth inhibitory effects of nano-TiO2 in algae occurred at concentrations lower than those that can elevate DCF fluorescence, and that ROS generation is not directly involved with the sublethal effects of nano-TiO2 in algae. PMID:25867689

  8. Spectral shifting by dyes to enhance algae growth.

    PubMed

    Prokop, A; Quinn, M F; Fekri, M; Murad, M; Ahmed, S A

    1984-11-01

    The photosynthetic growth action spectrum of a green alga at three bands of visible light (blue, orange, and red) at fixed quanta input and under light-limiting conditions was measured in a batch cultivation system. Quantum efficiencies (biomass dry weight increment per quanta absorbed) were better in the yellow-red region than in the blue region. Results served as a basis for the design and optimization of a dye system that would shift the energy of solar radiation to the required wavelength range by absorbing ultraviolet to blue radiation and emitting in the yellow-red, thus enhancing algae growth. Direct incorporation of dyes into the growth medium, although theoretically expected to enhance growth, in fact resulted in dye decomposition, toxicity to algae and consequently in growth inhibition. Indirect application of dyes in a double tubular reactor (algae inside and dye solution outside) demonstrated growth enhancement for certain dyes with high quantum yields and stability, which had suitable absorption/emission spectra for artificial light sources used. The maximum indirect growth enhancement was obtained using rhodamine 6G at a concentration of 3x10(-5)M with tungsten filament lamp sources. PMID:18551655

  9. Inhibitory effects of brown algae extracts on histamine production in mackerel muscle via inhibition of growth and histidine decarboxylase activity of Morganella morganii.

    PubMed

    Kim, Dong Hyun; Kim, Koth Bong Woo Ri; Cho, Ji Young; Ahn, Dong Hyun

    2014-04-01

    This study was performed to investigate the inhibitory effects of brown algae extracts on histamine production in mackerel muscle. First, antimicrobial activities of brown algae extracts against Morganella morganii were investigated using a disk diffusion method. An ethanol extract of Ecklonia cava (ECEE) exhibited strong antimicrobial activity. The minimum inhibitory concentration (MIC) of ECEE was 2 mg/ml. Furthermore, the brown algae extracts were examined for their ability to inhibit crude histidine decarboxylase (HDC) of M. morganii. The ethanol extract of Eisenia bicyclis (EBEE) and ECEE exhibited significant inhibitory activities (19.82% and 33.79%, respectively) at a concentration of 1 mg/ml. To obtain the phlorotannin dieckol, ECEE and EBEE were subjected to liquid-liquid extraction, silica gel column chromatography, and HPLC. Dieckol exhibited substantial inhibitory activity with an IC50 value of 0.61 mg/ml, and exhibited competitive inhibition. These extracts were also tested on mackerel muscle. The viable cell counts and histamine production in mackerel muscle inoculated with M. morganii treated with ≥2.5 MIC of ECEE (weight basis) were highly inhibited compared with the untreated sample. Furthermore, treatment of crude HDC-inoculated mackerel muscle with 0.5% ECEE and 0.5% EBEE (weight basis), which exhibited excellent inhibitory activities against crude HDC, reduced the overall histamine production by 46.29% and 56.89%, respectively, compared with the untreated sample. Thus, these inhibitory effects of ECEE and EBEE should be helpful in enhancing the safety of mackerel by suppressing histamine production in this fish species. PMID:24394193

  10. [Peculiarities of growth of the monocellular green algae culture after the influence of electromagnetic field in deuterated water-containing media].

    PubMed

    Semenov, K T; Aslanian, R R

    2013-01-01

    Exposing the inoculum of monocellular green algae Dunalialla tertiolecta and Tetraselmis viridis to 50 Hz electromagnetic field for several hours resulted in a reduced growth rate in both cultures. It was ascertained that heavy water inhibited growth of algae Dunaliella tertiolecta. The light water activated growth of the culture in the exponential phase only. PMID:23650857

  11. Determination of growth rate depression of some green algae by atrazine

    SciTech Connect

    Hersh, C.M.; Crumpton, W.G.

    1987-12-01

    A common contaminant of surface waters of agricultural regions is the triazine herbicide, atrazine (2-chloro-4-ethylamino-6-isoproplyamino-s-triazine). Atrazine effectively inhibits growth and photosynthesis of most plants, including freshwater algae. Both depression of growth rate and reduced yield have been used as parameters in studies of the effects of atrazine on algal growth. Considerable variation exists among algal toxicity methods despite attempts at standardization. Experimental endpoints range from percent inhibitions to EC50s. Algae from two different Iowa springs were the subjects of a study of naturally occurring atrazine tolerance. The authors report here the results of two aspects of that study: development of a quick method of assessing toxin effects on algal growth, and investigation of a ecologically meaningful endpoint for toxin-growth experiments.

  12. [Parameter determination of algae growth based on ecological tank experiment].

    PubMed

    Pang, Yong; Ding, Ling; Gao, Guang

    2005-05-01

    A dynamic simulation experiment of algae in an ecological tank was performed at the Taihu Laboratory for Lake Ecosystem Research. During the experiment, water from Taihu Lake was infused into the ecological tank and samples were taken continually to observe algae growth under varying conditions, such as temperature, sunlight and nutrients. Based on the experiment, an algae growth model, considering nitrogen and phosphorus cycle, was developed by using the advanced PHREEQC model. After that, a detailed calibration and validation of parameters in the model were done on the basis of experimental results. The least square method was used to determine the optimal set of parameters. The calculated values of algae and nutrient concentrations show fairly satisfying fittness with measured data. PMID:16124474

  13. Inhibitory effects of terpene alcohols and aldehydes on growth of green alga Chlorella pyrenoidosa

    SciTech Connect

    Ikawa, Miyoshi; Mosley, S.P.; Barbero, L.J. )

    1992-10-01

    The growth of the green alga Chlorella pyrenoidosa was inhibited by terpene alcohols and the terpene aldehyde citral. The strongest activity was shown by citral. Nerol, geraniol, and citronellol also showed pronounced activity. Strong inhibition was linked to acyclic terpenes containing a primary alcohol or aldehyde function. Inhibition appeared to be taking place through the vapor phase rather than by diffusion through the agar medium from the terpene-treated paper disks used in the system. Inhibition through agar diffusion was shown by certain aged samples of terpene hydrocarbons but not by recently purchased samples.

  14. The effects of barley straw (Hordeum vulgare) on the growth of freshwater algae.

    PubMed

    Ferrier, M D; Butler, B R; Terlizzi, D E; Lacouture, R V

    2005-11-01

    Bioassays were conducted to determine the efficacy of barley straw liquor in controlling algal growth of 12 freshwater species of algae representing three divisions. Barley straw liquor inhibited the growth of three nuisance algae common in freshwater: Synura petersenii, Dinobyron sp., and Microcystis aeruginosa. However, Selenastrum capricornutum, Spirogyra sp., Oscillatoria lutea var. contorta, and Navicula sp. had significantly increased growth in the presence of straw liquor. The growth of the remainder, Ulothrix fimbriata, Scenedesmus quadricauda, Chlorella vulgaris, Anabaena flos-aquae, and Synedra sp. showed no significant difference from controls. In a related field study, we treated four of six ponds with barley straw and monitored their chlorophyll a levels for one growing season. While phytoplankton populations in all ponds decreased in midsummer, the phytoplankton biomass in treated ponds did not differ significantly from that of control ponds, suggesting that the application of barley straw had no effect on algal growth in these systems. PMID:16051085

  15. Effects of artemisinin sustained-release granules on mixed alga growth and microcystins production and release.

    PubMed

    Ni, Lixiao; Li, Danye; Hu, Shuzhen; Wang, Peifang; Li, Shiyin; Li, Yiping; Li, Yong; Acharya, Kumud

    2015-12-01

    To safely and effectively apply artemisinin sustained-release granules to control and prevent algal water-blooms, the effects of artemisinin and its sustained-release granules on freshwater alga (Scenedesmus obliquus (S. obliquus) and Microcystis aeruginosa (M. aeruginosa)), as well as the production and release of microcystins (MCs) were studied. The results showed that artemisinin sustained-release granules inhibited the growth of M. aeruginosa (above 95% IR) and S. obliquus (about 90% IR), with M. aeruginosa more sensitive. The artemisinin sustained-release granules had a longer inhibition effect on growth of pure algae and algal coexistence than direct artemisinin dosing. The artemisinin sustained-release granules could decrease the production and release of algal toxins due to the continued stress of artemisinin released from artemisinin sustained-release granules. There was no increase in the total amount of MC-LR in the algal cell culture medium. PMID:26432265

  16. Phosphorus-limited growth of a green alga and a blue-green alga

    SciTech Connect

    Lang, D.S.; Brown, E.J.

    1981-12-01

    The phosphorus-limited growth kinetics of the chlorophyte Scenedesmus quadricauda and the cyanophyte Synechococcus Nageli were studied by using batch and continuous culturing techniques. The steady-state phosphate transport capability and the phosphorus storage capacity is higher in S. Nageli than in S. quadricauda. Synechococcus Nageli can also deplete phosphate to much lower levels than can S. quadricauda. These results, along with their morphological characteristics, were used to construct partial physiological profiles for each organism. The profiles indicate that this unicellular cyanophyte (cyanobacterium) is better suited for growth in phosphorus-limited oligotrophic niches than is this chlorophyte (green alga). (Refs. 44).

  17. Factors influencing stable isotopes and growth of algae in oil sands aquatic reclamation.

    PubMed

    Boutsivongsakd, Monique; Farwell, Andrea J; Chen, Hao; Dixon, D George

    2015-01-01

    Previous studies reported (15)N enrichment of biota in reclamation wetlands that contain oil sands processed material (e.g., processed water and tailings); however, there is little information on the factors controlling (15)N enrichment in these systems. In this microcosm study, the aim was to examine stable C and N isotopes and growth (chlorophyll a [chl a] and dry weight) of algae as a function of exposure to different sources and concentrations of water-soluble fractions (WSF) derived from tailings. Two sources of tailings including mature fine tailings (MFT) and consolidated tailings (CT) and peat-mineral overburden were utilized to generate separate WSF that differed in water quality. In general, there was (15)N enrichment of filamentous algae along the increasing gradient of WSF/nutrient concentrations in both CT and peat microcosms, and among the different sources, algae were more (15)N enriched in CT WSF than in peat WSF. Growth of filamentous algae was inhibited at higher WSF concentrations, possibly due to reduced light availability at elevated levels of fine clay particles in MFT microcosms and colored dissolved organic carbon (DOC) in peat microcosms. Filamentous algae displayed lower biomass and (15)N depletion in 100% peat WSF. This study indicated that both the quality (source) and quantity of WSF affected algal growth and directly and/or indirectly influenced δ(15)N of algae. The distinct (15)N enrichment of primary producers derived from tailings suggest that stable N isotopes might be useful to trace exposure to oil sands processed material in biota that utilize these resources in reclaimed systems constructed with tailings or natural systems that receive tailings dyke seepage. PMID:25506635

  18. Inhibition of three algae species using chemicals released from barley straw.

    PubMed

    Murray, D; Jefferson, B; Jarvis, P; Parsons, S A

    2010-04-01

    Algal blooms are a significant problem in the UK, particularly in water sources that supply potable water treatment works. A wide range of methods to control algae have been tested and, whilst many are effective, they all have disadvantages. The use of barley straw to control algal growth in reservoirs is one option that is gaining popularity, but little is known about its mode of action. One suggested mechanism is that, as the straw is broken down, algastatic chemicals such as phenolics are released. Here we have used an algae inhibition test to evaluate the effect of chemicals reported to be released from straw on three common algal species: Chlorella vulgaris, Microcystis aeruginosa and Scenedesmus subspicatus. It was shown that, of the chemicals assessed, many produced an algastatic effect on the growth of the three algal species tested, with 2 phenyl-phenol being the most effective, whilst p-cresol and benzaldehyde were shown to be effective at concentrations similar to those that have been reported downstream of rotted straw. Scenedesmus subspicatus proved to be much more resistant to the chemicals tested than the other species. PMID:20450120

  19. Algae.

    PubMed

    Raven, John A; Giordano, Mario

    2014-07-01

    Algae frequently get a bad press. Pond slime is a problem in garden pools, algal blooms can produce toxins that incapacitate or kill animals and humans and even the term seaweed is pejorative - a weed being a plant growing in what humans consider to be the wrong place. Positive aspects of algae are generally less newsworthy - they are the basis of marine food webs, supporting fisheries and charismatic marine megafauna from albatrosses to whales, as well as consuming carbon dioxide and producing oxygen. Here we consider what algae are, their diversity in terms of evolutionary origin, size, shape and life cycles, and their role in the natural environment and in human affairs. PMID:25004359

  20. Effects of lead on growth, photosynthetic characteristics and production of reactive oxygen species of two freshwater green algae.

    PubMed

    Dao, Ly H T; Beardall, John

    2016-03-01

    In the natural environment, heavy metal contamination can occur as long-term pollution of sites or as pulses of pollutants from wastewater disposal. In this study two freshwater green algae, Chlorella sp. FleB1 and Scenedesmus YaA6, were isolated from lead-polluted water samples and the effects of 24 h vs 4 and 8 d exposure of cultures to lead on growth, photosynthetic physiology and production of reactive oxygen species (ROS) of these algae were investigated. In Chlorella sp. FleB1, there was agreement between lead impacts on chlorophyll content, photosynthesis and growth in most case. However, in Scenedesmus acutus YaA6 growth was inhibited at lower lead concentrations (0.03-0.87 × 10(-9) M), under which ROS, measured by 2',7' dichlorodihydrofluorescein diacetate fluorescence, were 4.5 fold higher than in controls but photosynthesis was not affected, implying that ROS had played a role in the growth inhibition that did not involve direct effects on photosynthesis. Effects of short-term (5 h, 24 h) vs long-term (4 d and 8 d) exposure to lead were also compared between the two algae. The results contribute to our understanding of the mechanisms of lead toxicity to algae. PMID:26774308

  1. [Growth inhibition effect of immobilized pectinase on Microcystis aeruginosa].

    PubMed

    Shen, Qing-Qing; Peng, Qian; Lai, Yong-Hong; Ji, Kai-Yan; Han, Xiu-Lin

    2012-12-01

    To confirm the growth inhibition effect of immobilized pectinase on algae, co-cultivation method was used to investigate the effect of immobilized pectinase on the growth of Microcystis aeruginosa. After co-cultivation, the damage status of the algae was observed through electron microscope, and the effect of immobilized pectase on the physiological and biochemical characteristics of the algae was also measured. The results showed that the algae and immobilized pectase co-cultivated solution etiolated distinctly on the third day and there was a significantly positive correlation between the extent of etiolation and the dosage as well as the treating time of the immobilized pectinase. Under electron microscope, plasmolysis was found in the slightly damaged cells, and the cell surface of these cells was rough, uneven and irregular; the severely damaged cells were collapsed or disintegrated completely. The algal yield and the chlorophyll a content decreased significantly with the increase of the treating time. The measurement of the malondiadehyde (MDA) value showed that the antioxidation system of the treated algal cells was destroyed, and their membrane lipid was severely peroxidated. The study indicated that the immobilized pectinase could efficiently inhibit the growth of M. aeruginosa, and the inhibitory rate reached up to 96%. PMID:23379158

  2. Toluhydroquinone, the secondary metabolite of marine algae symbiotic microorganism, inhibits angiogenesis in HUVECs.

    PubMed

    Kim, Nan-Hee; Jung, Hyun-Il; Choi, Woo-Suk; Son, Byeng-Wha; Seo, Yong-Bae; Choi, Jae Sue; Kim, Gun-Do

    2015-03-01

    Angiogenesis, the growth of new blood vessels from the existing ones, occurs during embryo development and wound healing. However, most malignant tumors require angiogenesis for their growth and metastasis as well. Therefore, inhibition of angiogenesis has been focused as a new strategy of cancer therapies. To treat cancer, there are marine microorganism-derived secondary metabolites developed as chemotherapeutic agents. In this study, we used toluhydroquinone (2-methyl-1,4-hydroquinone), one of the secondary metabolites isolated from marine algae symbiotic fungus, Aspergillus sp. We examined the effects of toluhydroquinone on angiogenesis using HUVECs. We identified that toluhydroquinone inhibited the activity of β-catenin and down-regulated Ras/Raf/MEK/ERK signaling which are crucial components during angiogenesis. In addition, the expression and activity of MMPs are reduced by the treatment of toluhydroquinone. In conclusion, we confirmed that toluhydroquinone has inhibitory effects on angiogenic behaviors of human endothelial cells, HUVECs. Our findings suggest that toluhydroquinone can be proposed as a potent anti-angiogenesis drug candidate to treat cancers. PMID:25776491

  3. Salicylhydroxamic acid (SHAM) inhibition of the DIC-pump in unicellular algae

    SciTech Connect

    Goyal, A.; Tolbert, N.E. )

    1989-04-01

    SHAM at 1 or 2 mM inhibits dissolved inorganic carbon (DIC) concentrating mechanisms in unicellular green algae as measured by photosynthetic oxygen evolution or by {sup 14}C-inorganic carbon uptake (using silicone oil centrifugation techniques). This inhibition was reversed by high levels of DIC whereby the cells do not require the concentrating mechanism. SHAM inhibited the DIC-pump, which uses external CO{sub 2}, in three species of algae, Dunaliella tertiolecta, Chlamydomonas reinhardtii, and Scenedesmus obliquus when adapted to low CO{sub 2} and assayed around neutral pH. Scenedesmus adapted to air at pH 9.0 to use external HCO{sub 3}{sup {minus}} were not affected by SHAM. It is important to establish low optimum concentrations of SHAM, which varied with the algal species. The mechanism of SHAM inhibition of the CO{sub 2} concentrating process is unknown. SHAM inhibits alternative respiration in these algae, but SHAM may also inhibit other reactions involving H{sup +} gradients or transporters associated with the DIC-pump.

  4. Nitric oxide suppresses growth and development in the unicellular green alga Micrasterias denticulata.

    PubMed

    Lehner, Christine; Kerschbaum, Hubert H; Lütz-Meindl, Ursula

    2009-01-30

    Nitric oxide (NO), a key molecule in inter- and intracellular signalling, is implicated in developmental processes, host defense, and apoptosis in higher plants. We investigated the effect of NO on development in the unicellular green alga, Micrasterias denticulata, using two different NO donors, S-nitroso-N-acetyl-dl-penicillamine (SNAP) and sodium nitroprusside (SNP). Investigations at the light microsopic level revealed that both NO donors suppressed cell growth. Ultrastructural analyses were performed with SNAP- as well as SNP-treated cells and, additionally, with the control compound N-acetyl-d-penicillamine (NAP). Cells incubated with NO donors lacked a secondary wall and dictyosomal function was impaired, whereas NAP-treated cells showed no difference in development and organelle structure compared to control cells. Moreover, cisternae of the Golgi stacks were slightly involute and no vesicles were pinched off after SNAP and SNP incubation. The NO scavenger cPTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, potassium salt) abrogated the effect of SNP, thus confirming that inhibition of cell growth is due to nitric oxide. Addition of iodoacetic acid, an inhibitor of cysteine-containing enzymes, like glyceraldehyde-3-phosphate dehydrogenase (GAPDH), evoked similar effects on cell growth and secondary wall formation as obtained by treatment with NO donors. Therefore, we hypothesize that NO inhibits activity of enzymes involved in the secretory pathway, such as GAPDH, via S-nitrosylation of the cysteine residue and, consequently, modulates cell growth in M. denticulata. PMID:18455833

  5. The growth and harvesting of algae in a micro-gravity environment

    NASA Technical Reports Server (NTRS)

    Wiltberger, Nancy L.

    1987-01-01

    Algae growth in a micro-gravity environment is an important factor in supporting man's permanent presence in space. Algae can be used to produce food, oxygen, and pure water in a manned space station. A space station is one example of a situation where a Controlled Ecological Life Support System (CELSS) is imperative. In setting up a CELSS with an engineering approach at the Aerospace department of the University of Colorado, questions concerning algae growth in micro-g have arisen. The Get Away Special (GAS) Fluids Management project is a means through which many questions about the effects of a micro-g environment on the adequacy of growth rates, the viability of micro-organisms, and separation of gases and solids for harvesting purposes can be answered. In order to be compatible with the GAS tests, the algae must satisfy the following criteria: (1) rapid growth rates, (2) sustain viability over long periods of non-growth storage, and (3) very brief latency from storage to rapid growth. Testing indicates that the overall growth characteristics of Anacystis Nidulans satisfy the specifications of GAS's design constraints. In addition, data acquisition and the method of growth instigation are two specific problems being examined, as they will be encountered in interfacing with the GAS project. Flight testing will be two-fold, measurement of algae growth in micro-g and separation of algae from growth medium in an artificial gravitation field. Post flight results will provide information on algae viability in a micro-g environment as reflected by algal growth rates in space. Other post flight results will provide a basis for evaluating techniques for harvesting algae. The results from the GAS project will greatly assist the continuing effort of developing the CELSS and its applications for space.

  6. Uptake of caprolactam and its influence on growth and oxygen production of Desmodesmus quadricauda algae.

    PubMed

    Kalinová, Jana Pexová; Tříska, Jan; Vrchotová, Naděžda; Novák, Jan

    2016-06-01

    The consumption of polyamides produced from caprolactam is increasing continuously, and for that reason the danger of environmental contamination by this lactam is also rising. This study's aim was to evaluate the influence of caprolactam on the growth and oxygen production of the green alga Desmodesmus quadricauda and on caprolactam uptake by this alga. The presence of caprolactam in water was observed to cause the algae significantly to increase its oxygen production. Caprolactam concentration of 5,000 mg/L stopped algae growth after 6 days and influenced coenobia structure (seen as disappearance of pyrenoids, deformation of cells) but did not decrease the number of cells in the coenobia. Caprolactam uptake is probably passive but relatively rapid. Maximum concentration in the algae was reached after 18-24 h. PMID:26985739

  7. Studies on the hormonal relationships of algae in pure culture : I. The effect of indole-3-acetic acid on the growth of blue-green and green algae.

    PubMed

    Ahmad, M R; Winter, A

    1968-09-01

    Indole-3-acetic acid (IAA) stimulated the growth (increase in dry weight) of the blue-green algae Anacystis nidulans, Chlorogloea fritschii, Phormidium foveolarum, Nostoc muscorum, Anabaena cylindrica, and Tolypothrix tenuis and the green algae Chlorella pyrenoidosa, Ankistrodesmus falcatus and Scenedesmus obliquus growing under as sterile conditions as possible. The optimum concentration varied from species to species; in the blue-green algae it ranged from 10(-5) to 10(-9) M and in the green algae it was 10(-3) M. These results are discussed in the light of present studies in this field. PMID:24522736

  8. Well having inhibited microbial growth

    DOEpatents

    Lee, Brady D.; Dooley, Kirk J.

    2006-08-15

    The invention includes methods of inhibiting microbial growth in a well. A packing material containing a mixture of a first material and an antimicrobial agent is provided to at least partially fill a well bore. One or more access tubes are provided in an annular space around a casing within the well bore. The access tubes have a first terminal opening located at or above a ground surface and have a length that extends from the first terminal opening at least part of the depth of the well bore. The access tubes have a second terminal opening located within the well bore. An antimicrobial material is supplied into the well bore through the first terminal opening of the access tubes. The invention also includes well constructs.

  9. Salicylhydroxamic acid (SHAM) inhibition of the dissolved inorganic carbon concentrating process in unicellular green algae

    SciTech Connect

    Goyal, A.; Tolbert, N.E. )

    1990-03-01

    Rates of photosynthetic O{sub 2} evolution, for measuring K{sub 0.5}(CO{sub 2} + HCO{sub 3}{sup {minus}}) at pH 7, upon addition of 50 micromolar HCO{sub 3}{sup {minus}} to air-adapted Chlamydomonas, Dunaliella, or Scenedesmus cells, were inhibited up to 90% by the addition of 1.5 to 4.0 millimolar salicylhydroxamic acid (SHAM) to the aqueous medium. The apparent K{sub i}(SHAM) for Chlamydomonas cells was about 2.5 millimolar, but due to low solubility in water effective concentrations would be lower. Salicylhydroxamic acid did not inhibit oxygen evolution or accumulation of bicarbonate by Scenedesmus cells between pH 8 to 11 or by isolated intact chloroplasts from Dunaliella. Thus, salicylhydroxamic acid appears to inhibit CO{sub 2} uptake, whereas previous results indicate that vanadate inhibits bicarbonate uptake. These conclusions were confirmed by three test procedures with three air-adapted algae at pH 7. Salicylhydroxamic acid inhibited the cellular accumulation of dissolved inorganic carbon, the rate of photosynthetic O{sub 2} evolution dependent on low levels of dissolved inorganic carbon (50 micromolar NaHCO{sub 3}), and the rate of {sup 14}CO{sub 2} fixation with 100 micromolar ({sup 14}C)HCO{sub 3}{sup {minus}}. Salicylhydroxamic acid inhibition of O{sub 2} evolution and {sup 14}CO{sub 2}-fixation was reversed by higher levels of NaHCO{sub 3}. Thus, salicylhydroxamic acid inhibition was apparently not affecting steps of photosynthesis other than CO{sub 2} accumulation. Although salicylhydroxamic acid is an inhibitor of alternative respiration in algae, it is not known whether the two processes are related.

  10. Bioconvective patterns, synchrony, and survival. [in light-limited growth model of motile algae culture

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1990-01-01

    With and without bioconvective pattern formation, a theoretical model predicts growth in light-limited cultures of motile algae. At the critical density for pattern formation, the resulting doubly exponential population curves show an inflection. Such growth corresponds quantitatively to experiments in mechanically unstirred cultures. This attaches survival value to synchronized pattern formation.

  11. Inhibition of five natural products from Chinese herbs on the growth of Chattonella marina.

    PubMed

    Liu, Fei; He, Zheng-Bing; Li, Hong-Ye; Liu, Jie-Sheng; Yang, Wei-Dong

    2016-09-01

    The effects of five natural products from Chinese herbs including evodiamine, curcumin, 4-methoxysalicylaldehyde, esculin hydrate, and gramine on the growth of Chattonella marina, one of the most noxious red tide algae, were observed. Among them, gramine exhibited the highest inhibitory rate with LC50, 96h of 0.51 mg/l. After exposure to gramine, the activities of superoxide dismutase (SOD) and catalase (CAT), and content of malondialdehyde (MDA) increased in C. marina, suggesting that gramine could induce microalgae oxidative stress. In addition, chlorophyll a and the maximum quantum yield of photosynthesis (Fv/Fm) decreased following exposure to gramine, indicating the inhibition of photosynthesis activity in the microalgae. Combined with the fast inhibition against the algal cells and environmentally friendly character of gramine, we proposed that gramine might be a potential algaecide against marine harmful algae and that the oxidative damage and photosynthesis inhibition might be responsible for the toxicity of gramine on harmful algae. PMID:27250087

  12. Effects of chlorpyrifos on the growth and ultrastructure of green algae, Ankistrodesmus gracilis.

    PubMed

    Asselborn, Viviana; Fernández, Carolina; Zalocar, Yolanda; Parodi, Elisa R

    2015-10-01

    The effect of the organophosphorus insecticide chlorpyrifos on the growth, biovolume, and ultrastructure of the green microalga Ankistrodesmus gracilis was evaluated. Concentrations of 9.37, 18.75, 37.5, 75 and 150mgL(-1) of chlorpyrifos were assayed along with a control culture. At the end of the bioassay the ultrastructure of algal cells from control culture and from cultures exposed to 37.5 and 150mgL(-1) was observed under transmission (TEM) and scanning electron microscopy (SEM). After 24 and 48h, treatments with 75 and 150mgL(-1) inhibited the growth of A. gracilis; whereas after 72 and 96h, all the treatments except at 9.37mgL(-1) significantly affected the algae growth. The effective concentration 50 (EC50) after 96h was 22.44mgL(-1) of chlorpyrifos. After the exposure to the insecticide, an increase in the biovolume was observed, with a larger increase in cells exposed to 75 and 150mgL(-1). Radical changes were observed in the ultrastructure of cells exposed to chlorpyrifos. The insecticide affected the cell shape and the distribution of the crests in the wall. At 37.5mgL(-1) electodense bodies were observed along with an increase in the size and number of starch granules. At 150mgL(-1) such bodies occupied almost the whole cytoplasm together with lipids and remains of thylakoids. Autospores formation occurred normally at 37.5mgL(-1) while at 150mgL(-1) karyokinesis occurred, but cell-separation-phase was inhibited. The present study demonstrates that the exposure of phytoplankton to the insecticide chlorpyrifos leads to effects observed at both cellular and population level. PMID:26099464

  13. The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins

    PubMed Central

    Gong, An-Dong; Li, He-Ping; Shen, Lu; Zhang, Jing-Bo; Wu, Ai-Bo; He, Wei-Jie; Yuan, Qing-Song; He, Jing-De; Liao, Yu-Cai

    2015-01-01

    Aflatoxigenic Aspergillus fungi and associated aflatoxins are ubiquitous in the production and storage of food/feed commodities. Controlling these microbes is a challenge. In this study, the Shewanella algae strain YM8 was found to produce volatiles that have strong antifungal activity against Aspergillus pathogens. Gas chromatography-mass spectrometry profiling revealed 15 volatile organic compounds (VOCs) emitted from YM8, of which dimethyl trisulfide was the most abundant. We obtained authentic reference standards for six of the VOCs; these all significantly reduced mycelial growth and conidial germination in Aspergillus; dimethyl trisulfide and 2,4-bis(1,1-dimethylethyl)-phenol showed the strongest inhibitory activity. YM8 completely inhibited Aspergillus growth and aflatoxin biosynthesis in maize and peanut samples stored at different water activity levels, and scanning electron microscopy revealed severely damaged conidia and a complete lack of mycelium development and conidiogenesis. YM8 also completely inhibited the growth of eight other agronomically important species of phytopathogenic fungi: A. parasiticus, A. niger, Alternaria alternate, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Monilinia fructicola, and Sclerotinia sclerotiorum. This study demonstrates the susceptibility of Aspergillus and other fungi to VOCs from marine bacteria and indicates a new strategy for effectively controlling these pathogens and the associated mycotoxin production during storage and possibly in the field. PMID:26500631

  14. The Shewanella algae strain YM8 produces volatiles with strong inhibition activity against Aspergillus pathogens and aflatoxins.

    PubMed

    Gong, An-Dong; Li, He-Ping; Shen, Lu; Zhang, Jing-Bo; Wu, Ai-Bo; He, Wei-Jie; Yuan, Qing-Song; He, Jing-De; Liao, Yu-Cai

    2015-01-01

    Aflatoxigenic Aspergillus fungi and associated aflatoxins are ubiquitous in the production and storage of food/feed commodities. Controlling these microbes is a challenge. In this study, the Shewanella algae strain YM8 was found to produce volatiles that have strong antifungal activity against Aspergillus pathogens. Gas chromatography-mass spectrometry profiling revealed 15 volatile organic compounds (VOCs) emitted from YM8, of which dimethyl trisulfide was the most abundant. We obtained authentic reference standards for six of the VOCs; these all significantly reduced mycelial growth and conidial germination in Aspergillus; dimethyl trisulfide and 2,4-bis(1,1-dimethylethyl)-phenol showed the strongest inhibitory activity. YM8 completely inhibited Aspergillus growth and aflatoxin biosynthesis in maize and peanut samples stored at different water activity levels, and scanning electron microscopy revealed severely damaged conidia and a complete lack of mycelium development and conidiogenesis. YM8 also completely inhibited the growth of eight other agronomically important species of phytopathogenic fungi: A. parasiticus, A. niger, Alternaria alternate, Botrytis cinerea, Fusarium graminearum, Fusarium oxysporum, Monilinia fructicola, and Sclerotinia sclerotiorum. This study demonstrates the susceptibility of Aspergillus and other fungi to VOCs from marine bacteria and indicates a new strategy for effectively controlling these pathogens and the associated mycotoxin production during storage and possibly in the field. PMID:26500631

  15. Comparing the Effects of Symbiotic Algae (Symbiodinium) Clades C1 and D on Early Growth Stages of Acropora tenuis

    PubMed Central

    Yuyama, Ikuko; Higuchi, Tomihiko

    2014-01-01

    Reef-building corals switch endosymbiotic algae of the genus Symbiodinium during their early growth stages and during bleaching events. Clade C Symbiodinium algae are dominant in corals, although other clades — including A and D — have also been commonly detected in juvenile Acroporid corals. Previous studies have been reported that only molecular data of Symbiodinium clade were identified within field corals. In this study, we inoculated aposymbiotic juvenile polyps with cultures of clades C1 and D Symbiodinium algae, and investigated the different effect of these two clades of Symbiodinium on juvenile polyps. Our results showed that clade C1 algae did not grow, while clade D algae grew rapidly during the first 2 months after inoculation. Polyps associated with clade C1 algae exhibited bright green fluorescence across the body and tentacles after inoculation. The growth rate of polyp skeletons was lower in polyps associated with clade C1 algae than those associated with clade D algae. On the other hand, antioxidant activity (catalase) of corals was not significantly different between corals with clade C1 and clade D algae. Our results suggested that clade D Symbiodinium algae easily form symbiotic relationships with corals and that these algae could contribute to coral growth in early symbiosis stages. PMID:24914677

  16. Comparing the effects of symbiotic algae (Symbiodinium) clades C1 and D on early growth stages of Acropora tenuis.

    PubMed

    Yuyama, Ikuko; Higuchi, Tomihiko

    2014-01-01

    Reef-building corals switch endosymbiotic algae of the genus Symbiodinium during their early growth stages and during bleaching events. Clade C Symbiodinium algae are dominant in corals, although other clades - including A and D - have also been commonly detected in juvenile Acroporid corals. Previous studies have been reported that only molecular data of Symbiodinium clade were identified within field corals. In this study, we inoculated aposymbiotic juvenile polyps with cultures of clades C1 and D Symbiodinium algae, and investigated the different effect of these two clades of Symbiodinium on juvenile polyps. Our results showed that clade C1 algae did not grow, while clade D algae grew rapidly during the first 2 months after inoculation. Polyps associated with clade C1 algae exhibited bright green fluorescence across the body and tentacles after inoculation. The growth rate of polyp skeletons was lower in polyps associated with clade C1 algae than those associated with clade D algae. On the other hand, antioxidant activity (catalase) of corals was not significantly different between corals with clade C1 and clade D algae. Our results suggested that clade D Symbiodinium algae easily form symbiotic relationships with corals and that these algae could contribute to coral growth in early symbiosis stages. PMID:24914677

  17. [Growth inhibition and mechanism of cetyltrimethyl ammonium chloride on Chlorella vulgaris].

    PubMed

    Xu, Yin; Ge, Fei; Tao, Neng-Guo; Zhu, Run-Liang; Wang, Na

    2009-06-15

    Growth inhibition of cetyltrimethyl ammonium chloride (CTAC), a cationic surfactants, on Chlorella vulgaris was investigated at batch culture in laboratory. Furthermore, the corresponding mechanisms were studied by the determination of absorption capacity, Zeta potential, activity of acid phosphatase and ultrastructure of algae. Results show that the growth inhibition by CATC is enhanced with its concentration increasing from 0.1 mg/L to 1 mg/L, and 96 h-EC50 of CTAC is 0.18 mg/L. In the presence of 0.3 mg/L CTAC in 8 d, the inhibition efficiency of biomass reaches 70.7%. Meanwhile, the absorption of nitrogen and iron is inhibited 83.9% and 86.2% respectively with Zeta potential of algae cell increasing from -12.5 mV to -6.7 mV. Furthermore, the relative activity of acid phosphatase declines to 23.1% at the same time. Plasmolysis, distortion of pyrenoid and swelling of lysosome is observed in the cell. Above phenomena indicates that CTAC increases the Zeta potential of algae cell and thus inhibites the absorption of nitrogen and iron. In addition, CTAC may affect the metabolism of phosphorus and change the ultrastructure of algae cell. PMID:19662866

  18. Responses of marine unicellular algae to brominated organic compounds in six growth media

    SciTech Connect

    Walsh, G.E.; Yoder, M.J.; McLaughlin, L.L.; Lores, E.M.

    1987-12-01

    Marine unicellular algae, Skeletonema costatum, Thalassiosira pseudonana, and Chlorella sp. were exposed to the industrial brominated compounds tetrabromobisphenol A, decabromobiphenyloxide (DBBO), hexabromocyclododecane (HBCD), pentabromomethylbenzene (PBMB), pentabromoethylbenzene (PBEB), and the herbicide bromoxynil (BROM), in six algal growth media. High concentrations of DBBO (1 mg liter-1), PBMB (1 mg liter-1), and PBEB (0.5 mg liter-1) reduced growth by less than 50%. EC50s of the other compounds varied with growth medium, with high EC50/low EC50 ratios between 1.3 and 9.9. Lowest EC50s, 9.3 to 12.0 micrograms liter-1, were obtained with S. costatum and HBCD. It is concluded that responses to toxicants in different media are the results of interactions among algae, growth medium, toxicant, and solvent carrier.

  19. Effects on growth, antioxidant enzyme activity and levels of extracellular proteins in the green alga Chlorella vulgaris exposed to crude cyanobacterial extracts and pure microcystin and cylindrospermopsin.

    PubMed

    Campos, Alexandre; Araújo, Pedro; Pinheiro, Carlos; Azevedo, Joana; Osório, Hugo; Vasconcelos, Vitor

    2013-08-01

    Toxic cyanobacteria and cyanotoxins have been pointed as important players in the control of phytoplankton diversity and species abundance, causing ecological unbalances and contamination of the environment. In vitro experiments have been undertaken to address the impact of toxic cyanobacteria in green algae. In this regard the aim of this work was to compare the toxicity of two cyanobacteria species, Aphanizomenon ovalisporum and Microcystis aeruginosa, to the green alga Chlorella vulgaris by assessing culture growth when exposed for three and seven days to (I) cyanobacterial cell extracts and (II) pure toxins microcystin-LR (MC-LR) and cylindrospermopsin (CYN). The biochemical response of the green alga to pure toxins was also characterized, through the activity of the antioxidant markers glutathione S-transferase (GST) and glutathione peroxidase (GPx) and the expressed extracellular proteins in seven-day exposed cultures. A. ovalisporum crude extracts were toxic to C. vulgaris. Pure toxins up to 179.0 µg/L, on the other hand, stimulated the green alga growth. Growth results suggest that the toxicity of A. ovalisporum extracts is likely due to a synergistic action of CYN and other metabolites produced by the cyanobacterium. Regarding the green alga antioxidant defense mechanism, CYN at 18.4 and 179.0 µg/L increased the activity of GPx and GST while MC-LR inhibited the enzymes' activity at a concentration of 179.0 µg/L demonstrating a contrasting mode of action. Moreover the identification of F-ATPase subunit, adenylate cyclase, sulfate ABC transporter, putative porin, aspartate aminotransferase, methylene-tetrahydrofolate dehydrogenase and chlorophyll a binding proteins in the culture medium of C. vulgaris indicates that biochemical processes involved in the transport of metabolites, photosynthesis and amino acid metabolism are affected by cyanobacterial toxins and may contribute to the regulation of green alga growth. PMID:23726538

  20. Inhibition of nitrification in municipal wastewater-treating photobioreactors: Effect on algal growth and nutrient uptake.

    PubMed

    Krustok, I; Odlare, M; Truu, J; Nehrenheim, E

    2016-02-01

    The effect of inhibiting nitrification on algal growth and nutrient uptake was studied in photobioreactors treating municipal wastewater. As previous studies have indicated that algae prefer certain nitrogen species to others, and because nitrifying bacteria are inhibited by microalgae, it is important to shed more light on these interactions. In this study allylthiourea (ATU) was used to inhibit nitrification in wastewater-treating photobioreactors. The nitrification-inhibited reactors were compared to control reactors with no ATU added. Microalgae had higher growth in the inhibited reactors, resulting in a higher chlorophyll a concentration. The species mix also differed, with Chlorella and Scenedesmus being the dominant genera in the control reactors and Cryptomonas and Chlorella dominating in the inhibited reactors. The nitrogen speciation in the reactors after 8 days incubation was also different in the two setups, with N existing mostly as NH4-N in the inhibited reactors and as NO3-N in the control reactors. PMID:26716890

  1. Isolation, growth, ultrastructure, and metal tolerance of the green alga, Chlamydomonas acidophila (Chlorophyta).

    PubMed

    Nishikawa, K; Tominaga, N

    2001-12-01

    An acidophilic volvocine flagellate, Chlamydomonas acidophila (Volvocales) that was isolated from an acid lake, Katanuma, in Miyagi prefecture, Japan was studied for growth, ultrastructural characterization, and metal tolerance. Chlamydomonas acidophila is obligately photoautotrophic, and did not grow in the cultures containing acetate or citrate even in the light. The optimum pH for growth was 3.5-4.5. To characterize metal tolerance, the toxic effects of Cd, Co, Cu, and Zn on this alga were also studied. Effective metal concentrations, which limited the growth by 50%, EC50 were measured, after 72 h of static exposure. EC50s were 14.4 microM Cd2+, 81.3 microM Co2+, 141 microM Cu2+, and 1.16 mM Zn2+ for 72 h of exposure. Thus, this alga had stronger tolerance to these metals than other species in the genus Chlamydomonas. PMID:11826960

  2. Preparation of copper-chelate quaternized carboxymethyl chitosan/organic rectorite nanocomposites for algae inhibition.

    PubMed

    Cai, Jihai; Ye, Weijie; Wang, Xiaoying; Lin, Wensheng; Lin, Qixuan; Zhang, Qiang; Wu, Fangchengyuan

    2016-10-20

    Quaternized carboxymethyl chitosan/organic rectorite (QCMC/OREC) nanocomposites were rapidly prepared by intercalating QCMC into the layer of OREC under microwave irradiation. And then copper-chelate QCMC/OREC (QCMC/OREC-Cu) nanocomposites were obtained by mixing QCMC/OREC with CuSO4 solution. XRD and TEM results indicated that QCMC/OREC nanocomposites were obtained and QCMC was dispersed in the interlayer of OREC. Besides, FT-IR results revealed that the hydrogen bonds and electrostatic interaction in QCMC/OREC-Cu were both stronger than those in QCMC/OREC because of introducing the Cu(2+). The thermogravimetric analysis showed that the thermal stability of QCMC/OREC-Cu nanocomposites was higher than QCMC and QCMC/OREC. Algae inhibition assay revealed that QCMC/OREC-Cu nanocomposites had stronger antifouling activity than original QCMC and QCMC/OREC. This work provides important basis for developing novel antifouling materials. PMID:27474551

  3. Polyketides from an Endophytic Aspergillus fumigatus Isolate Inhibit the Growth of Mycobacterium tuberculosis and MRSA.

    PubMed

    Flewelling, Andrew J; Bishop, Amanda I; Johnson, John A; Gray, Christopher A

    2015-10-01

    The crude extract of Aspergillusfumigatus isolate AF3-093A, an endophyte of the brown alga Fucus vesiculosus, showed significant antimicrobial activity in initial bioactivity screens. Bioassay-guided fractionation of the extract led to the isolation of flavipin, chaetoglobosin A and chaetoglobosin B, all of which inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus and Mycobacterium tuberculosis H37Ra. The antimycobacterial activity of these compounds has not been previously reported. PMID:26669098

  4. Azoxystrobin-induced excessive reactive oxygen species (ROS) production and inhibition of photosynthesis in the unicellular green algae Chlorella vulgaris.

    PubMed

    Liu, Lei; Zhu, Bin; Wang, Gao-Xue

    2015-05-01

    This study investigated the short-term toxicity of azoxystrobin (AZ), one of strobilurins used as an effective fungicidal agent to control the Asian soybean rust, on aquatic unicellular algae Chlorella vulgaris. The median percentile inhibition concentration (IC₅₀) of AZ for C. vulgaris was found to be 510 μg L(-1). We showed that the algal cells were obviously depressed or shrunk in 300 and 600 μg L(-1) AZ treatments by using the electron microscopy. Furthermore, 19, 75, and 300 μg L(-1) AZ treatments decreased the soluble protein content and chlorophyll concentrations in C. vulgaris and altered the energy-photosynthesis-related mRNA expression levels in 48- and 96-h exposure periods. Simultaneously, our results showed that AZ could increase the total antioxidant capacity (T-AOC) level and compromise superoxide dismutase (SOD), peroxidase (POD), glutathione S transferase (GST), glutathione peroxidase (GPx) activities, and glutathione (GSH) content. These situations might render C. vulgaris more vulnerable to oxidative damage. Overall, the present study indicated that AZ might be toxic to the growth of C. vulgaris, affect energy-photosynthesis-related mRNA expressions, and induce reactive oxygen species (ROS) overproduction in C. vulgaris. PMID:25672875

  5. Growth condition study of algae function in ecosystem for CO2 bio-fixation.

    PubMed

    Tsai, David Dah-Wei; Ramaraj, Rameshprabu; Chen, Paris Honglay

    2012-02-01

    Algae niche play a crucial role on carbon cycle and have great potential for CO(2) sequestration. This study was to investigate the CO(2) bio-fixation by the high rate pond (HRP) to mimic the algae function of nature. All the reactors can keep CO(2) consumption efficiencies over 100%. The statistical analyses proved HRPs were close to the natural system from all the growth conditions. The HRP could show the "natural optimization as nature" to perform as well as the artificial reactor of continuously stirred tank reactor (CSTR). In the nutrition study, the carbon mass balance indicated CO(2) was the main carbon source. Accordingly, the HRPs can keep a neutral pH range to provide dissolved oxygen (DO), to promote total nitrogen (TN)/total phosphorous (TP) removal efficiencies and to demonstrate self-purification process. Furthermore, the observations of different nitrogen species in the reactors demonstrated that the major nitrogen source was decided by pH. This finding logically explained the complex nitrogen uptake by algae in nature. Consequently, this study took advantage of HRP to explore the processes of efficient CO(2) uptake with the corresponding growth condition in the ecosystem. Those results contributed the further understanding of the role of CO(2) bio-fixation in nature and demonstrated HRP could be a potential ecological engineering alternative. PMID:22196805

  6. Inhibition of Vascularization in Tumor Growth

    NASA Astrophysics Data System (ADS)

    Scalerandi, M.; Sansone, B. Capogrosso

    2002-11-01

    The transition to a vascular phase is a prerequisite for fast tumor growth. During the avascular phase, the neoplasm feeds only from the (relatively few) existing nearby blood vessels. During angiogenesis, the number of capillaries surrounding and infiltrating the tumor increases dramatically. A model which includes physical and biological mechanisms of the interactions between the tumor and vascular growth describes the avascular-vascular transition. Numerical results agree with clinical observations and predict the influence of therapies aiming to inhibit the transition.

  7. Growth and Metabolism of the Green Alga, Chlorella Pyrenoidosa, in Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Mills, W. Ronald

    2003-01-01

    The effect of microgravity on living organisms during space flight has been a topic of interest for some time, and a substantial body of knowledge on the subject has accumulated. Despite this, comparatively little information is available regarding the influence of microgravity on algae, even though it has been suggested for long duration flight or occupancy in space that plant growth systems, including both higher plants and algae, are likely to be necessary for bioregenerative life support systems. High-Aspect-Ratio Rotating-Wall Vessel or HARV bioreactors developed at Johnson Space Center provide a laboratory-based approach to investigating the effects of microgravity on cellular reactions. In this study, the HARV bioreactor was used to examine the influence of simulated microgravity on the growth and metabolism of the green alga, Chlorella pyrenoidosa. After the first 2 days of culture, cell numbers increased more slowly in simulated microgravity than in the HARV gravity control; after 7 days, growth in simulated microgravity was just over half (58%) that of the gravity control and at 14 days it was less than half (42%). Chlorophyll and protein were also followed as indices of cell competence and function; as with growth, after 2-3 days, protein and chlorophyll levels were reduced in modeled microgravity compared to gravity controls. Photosynthesis is a sensitive biochemical index of the fitness of photosynthetic organisms; thus, CO2-dependent O2 evolution was tested as a measure of photosynthetic capacity of cells grown in simulated microgravity. When data were expressed with respect to cell number, modeled microgravity appeared to have little effect on CO2 fixation. Thus, even though the overall growth rate was lower for cells cultured in microgravity, the photosynthetic capacity of the cells appears to be unaffected. Cells grown in simulated microgravity formed loose clumps or aggregates within about 2 days of culture, with aggregation increasing over time

  8. [Annual variation of different phosphorus forms and response of algae growth in Meiliang bay of Taihu Lake].

    PubMed

    Wang, Ming; Wu, Xiao-fei; Li, Da-peng; Li, Xiang; Huang, Yong

    2015-01-01

    Based on the monthly investigations of different forms of phosphorus(P) and algae growth from January to December 2013 in Meiliang bay of Taihu Lake, the transformation of different P forms and the relationship between different P forms and algae growth was investigated under the dual conditions of disturbance due to wind and wave and algae growth. Results of the total P(TP), particulate P (PP), dissolved total P(DTP), dissolved inorganic P(DIP) and bioavailable P(BAP) showed that the monthly concentrations reached the maximum in summer and autumn while the minimum in winter and spring. In addition, the algae growth showed the same trends as above. However, no variation was found in the dissolved organic P(DOP) and bioavailable particulate P(BAPP). The bioavailability of PP was only 12.75% from June to October, which was obviously lower than the annual mean (37.14%). It was attributed to the acceleration on the transformation of PP to DTP due to the immobilization of sedimentary P under sediment disturbance and algae adsorption. The percentage of DTP in BAP was up to 69.33% (average), which was obviously higher than the percentage of bioavailable PP (30.66%, average) and the annual mean (56.63%) of DTP during the interval. In addition, the algae bloom appeared in the interval. PMID:25898650

  9. Effect of wastewater-borne bacteria on algal growth and nutrients removal in wastewater-based algae cultivation system.

    PubMed

    Ma, Xiaochen; Zhou, Wenguang; Fu, Zongqiang; Cheng, Yanling; Min, Min; Liu, Yuhuan; Zhang, Yunkai; Chen, Paul; Ruan, Roger

    2014-09-01

    Centrate, a type of nutrient-rich municipal wastewater was used to determine the effect of wastewater-borne bacteria on algal growth and nutrients removal efficiency in this study. The characteristics of algal and bacterial growth profiles, wastewater nutrient removal and effect of initial algal inoculums were systematically examined. The results showed that initial algal concentration had apparent effect on bacterial growth, and the presence of bacteria had a significant influence on algal growth pattern, suggesting symbiotic relationship between algae and bacteria at the initial stage of algae cultivation. The maximum algal biomass of 2.01 g/L with 0.1g/L initial algal inoculums concentration can be obtained during algae cultivation in raw centrate medium. The synergistic effect of centrate-borne bacteria and microalgae on algae growth and nutrient removal performance at initial fast growth stage has great potential to be applied to pilot-scale wastewater-based algae wastewater system cultivated in continuous or semi-continuous mode. PMID:24968106

  10. Sludge-grown algae for culturing aquatic organisms: Part I. Algal growth in sludge extracts

    NASA Astrophysics Data System (ADS)

    Hung, K. M.; Chiu, S. T.; Wong, M. H.

    1996-05-01

    This project is aimed at studying the feasibility of using sewage sludge to prepare culture media for microalgae ( Chlorella-HKBU) and the use of the sludge-grown algae as a feed for some aquatic organisms. Part I of the project included results on preparing sludge extracts and their use on algal culture. By comparing two culturing techniques, “aeration” and “shaking,” it was noted that both lag and log phases were shortened in the aeration system. A subsequent experiment noted that algal growth subject to aeration rates of 1.0 and 1.5 liters/min had similar lag and log phases. In addition, both aeration rates had a significantly higher ( P < 0.05) final cell density than that of 0.5 liters/min. A detailed study on the variation of growth conditions on the algal growth was done. The results indicated that pH values of all the cultures declined below 5 at day 12. The removal rates of ammonia N ranged from 62% to 70%. The sludge-grown algae contained a rather substantial amount of heavy metals (µg/g): Zn 289 581, Cu 443 682, Ni 310 963, Mn 96 126, Cr 25 118, and Fe 438 653. This implied that the rather high levels of heavy metals may impose adverse effects on higher trophic organisms.

  11. Aqueous Extracts of the Marine Brown Alga Lobophora variegata Inhibit HIV-1 Infection at the Level of Virus Entry into Cells

    PubMed Central

    Kremb, Stephan; Helfer, Markus; Kraus, Birgit; Wolff, Horst; Wild, Christian; Schneider, Martha; Voolstra, Christian R.; Brack-Werner, Ruth

    2014-01-01

    In recent years, marine algae have emerged as a rich and promising source of molecules with potent activities against various human pathogens. The widely distributed brown alga Lobophora variegata that is often associated with tropical coral reefs exerts strong antibacterial and antiprotozoal effects, but so far has not been associated with specific anti-viral activities. This study investigated potential HIV-1 inhibitory activity of L. variegata collected from different geographical regions, using a cell-based full replication HIV-1 reporter assay. Aqueous L. variegata extracts showed strong inhibitory effects on several HIV-1 strains, including drug-resistant and primary HIV-1 isolates, and protected even primary cells (PBMC) from HIV-1-infection. Anti-viral potency was related to ecological factors and showed clear differences depending on light exposition or epiphyte growth. Assays addressing early events of the HIV-1 replication cycle indicated that L. variegata extracts inhibited entry of HIV-1 into cells at a pre-fusion step possibly by impeding mobility of virus particles. Further characterization of the aqueous extract demonstrated that even high doses had only moderate effects on viability of cultured and primary cells (PBMCs). Imaging-based techniques revealed extract effects on the plasma membrane and actin filaments as well as induction of apoptosis at concentrations exceeding EC50 of anti-HIV-1 activity by more than 400 fold. In summary, we show for the first time that L. variegata extracts inhibit HIV-1 entry, thereby suggesting this alga as promising source for the development of novel HIV-1 inhibitors. PMID:25144758

  12. ALGAE AND CRUSTACEANS AS INDICATORS OF BIOACTIVITY OF INDUSTRIAL WASTES

    EPA Science Inventory

    Freshwater (Selenastrum capricornutum) and estuarine (Skeketonema costatum) algae were exposed to liquid wastes from 10 industrial sites in laboratory bioassays. All wastes affected algal growth either by stimulation or by stimulation at low concentrations and inhibition at high ...

  13. Alpha-amylase Inhibition and Antioxidant Activity of Marine Green Algae and its Possible Role in Diabetes Management

    PubMed Central

    Unnikrishnan, P. S.; Suthindhiran, K.; Jayasri, M. A.

    2015-01-01

    Aim: In the continuing search for safe and efficient antidiabetic drug, marine algae become important source which provide several compounds of immense therapeutic potential. Alpha-amylase, alpha-glucosidase inhibitors, and antioxidant compounds are known to manage diabetes and have received much attention recently. In the present study, four green algae (Chaetomorpha aerea, Enteromorpha intestinalis, Chlorodesmis, and Cladophora rupestris) were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro. Materials and Methods: The phytochemical constituents of all the extracts were qualitatively determined. Antidiabetic activity was evaluated by inhibitory potential of extracts against alpha-amylase and alpha-glucosidase by spectrophotometric assays. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide (H2O2), and nitric oxide scavenging assay. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out to determine the major compound responsible for its antidiabetic action. Results: Among the various extracts screened, chloroform extract of C. aerea (IC50 − 408.9 μg/ml) and methanol extract of Chlorodesmis (IC50 − 147.6 μg/ml) showed effective inhibition against alpha-amylase. The extracts were also evaluated for alpha-glucosidase inhibition, and no observed activity was found. Methanol extract of C. rupestris showed notable free radical scavenging activity (IC50 – 666.3 μg/ml), followed by H2O2 (34%) and nitric oxide (49%). Further, chemical profiling by GC-MS revealed the presence of major bioactive compounds. Phenol, 2,4-bis (1,1-dimethylethyl) and z, z-6,28-heptatriactontadien-2-one were predominantly found in the methanol extract of C. rupestris and chloroform extract of C. aerea. Conclusion: Our results demonstrate that the selected algae exhibit notable alpha-amylase inhibition and antioxidant activity. Therefore, characterization of active compounds and its in vivo

  14. Inhibition of growth of Ulva expansa (chlorophyta) by ultraviolet-B radiation

    SciTech Connect

    Grobe, C.W.; Murphy, T.M.

    1994-10-01

    We examined the effect of ultraviolet-B radiation (UV-B, 290-320 nm) on the growth rate of the intertidal marine alga Ulva expansa (Setch.) S & G. (Chlorophyta). Segments of thallus collected from a natural population were grown in outdoor seawater tanks. Combinations of UV-B-opaque screens, UV-B transparent screens, and UV-B lamps were used to investigate the effects of solar UV-B and solar plus supplemental UV-B on the growth of these segments. Growth was measured by changes in segment surface area, damp weight, and dry weight. Growth rates of segments were inhibited under both solar UV-B and solar plus supplemental UV-B treatments. Growth rates were also inhibited by high levels of photosynthetically active radiation, independent of UV-B fluence. These results indicate that increases in UV-B resulting from further ozone depletion will have a negative impact on the growth of this alga. 32 refs., 5 figs., 2 tabs.

  15. Ormeloxifene efficiently inhibits ovarian cancer growth

    PubMed Central

    Maher, Diane M.; Khan, Sheema; Nordquist, Jordan; Ebeling, Mara C.; Bauer, Nichole A.; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C.; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer. PMID:25306892

  16. Growth and photosynthetic response of a freshwater alga, Selenastrum capricornutum, to an oil shale by-product water

    SciTech Connect

    Delistraty, D.

    1986-01-01

    Several recent studies have focused on toxic effects of various oil shale waters to freshwater algae (e.g., Cleave et al. 1980; McKnight et al. 1983). Algal bioassays are ecologically significant, since algae are the dominant primary producers in most freshwater environments. Furthermore, algae have been shown to be more sensitive to complex wastes than fish or invertebrates. Using a standard algal species provides a systematic approach to toxicant evaluation. One such species is Selenastrum capricornutum Printz, a freshwater unicellular green alga. A strategy to assess the hazards of complex effluents should include a battery of rapid, easily conducted, predictive tests within the larger framework of tier testing. This approach is used in this study to compare the growth and photosynthetic response of S. capricornutum to an oil shale by-product water and its organophilic and hydrophilic subfractions.

  17. Effects of algae growth on cadmium remobilization and ecological risk in sediments of Taihu Lake.

    PubMed

    Ni, Lixiao; Li, Dandan; Su, Lili; Xu, Jiajun; Li, Shiyin; Ye, Xiang; Geng, Hong; Wang, Peifang; Li, Yi; Li, Yiping; Acharya, Kumud

    2016-05-01

    Indoor simulation experiment with 2.76 L microcosms using sediment from Taihu Lake were conducted to investigate the relationship between algae bloom and heavy metals release into a lake aquatic environment. The results showed that Microcystic aeruginosa (M. aeruginosa) growth can enhance cadmium (Cd) mobilization from sediments to overlying water due to increasing pH and DO content of overlying water and changing the redox condition of surface sediment (0-2 cm) from weak oxidation to weak reduction. The dissolved Cd concentration in overlying water can be decreased during algal growth process. The remobilization of Cd from sediment can effectively reduce the ecological risk of total Cd in sediments. The results of this study showed that both Igeo and Er(i) can be used to effectively evaluate the ecological risk of heavy metal Cd in different fractions. PMID:26923240

  18. Effect propagation in a toxicokinetic/toxicodynamic model explains delayed effects on the growth of unicellular green algae Scenedesmus vacuolatus.

    PubMed

    Vogs, Carolina; Bandow, Nicole; Altenburger, Rolf

    2013-04-01

    Ecotoxicological standard tests assess toxic effects by exposing an organism to high concentrations over defined periods of time. To evaluate toxicity under field conditions such as fluctuating and pulsed exposures, process-based toxicokinetic/toxicodynamic (TK/TD) models may be used for extrapolation from the existing evidence. A TK/TD model was developed that simulates the effect on growth of the green algae Scenedesmus vacuolatus continuously exposed to the model chemicals norflurazon, triclosan, and N-phenyl-2-naphthylamine. A pharmacological time-response model describing the effects of anticancer treatments on cancer cell growth was adapted and modified to model the affected growth of synchronized algae cells. The TK/TD model simulates the temporal effect course by linking the ambient concentration of a chemical to the observable adverse effect via an internal concentration and a sequence of biological events in the organism. The parameters of the toxicodynamic model are related to the growth characteristics of algae cells, a no effect concentration, the chemical efficacy as well as the ability of recovery and repair, and the delay during damage propagation. The TK/TD model fits well to the observed algae growth. The effect propagation through cumulative cell damage explained the observed delayed responses better than just the toxicokinetics. The TK/TD model could facilitate the link between several effect levels within damage propagation, which prospectively may be helpful to model adverse outcome pathways and time-dependent mixture effects. PMID:23359135

  19. Selenium nanoparticles inhibit Staphylococcus aureus growth

    PubMed Central

    Tran, Phong A; Webster, Thomas J

    2011-01-01

    Staphylococcus aureus is a key bacterium commonly found in numerous infections. S. aureus infections are difficult to treat due to their biofilm formation and documented antibiotic resistance. While selenium has been used for a wide range of applications including anticancer applications, the effects of selenium nanoparticles on microorganisms remain largely unknown to date. The objective of this in vitro study was thus to examine the growth of S. aureus in the presence of selenium nanoparticles. Results of this study provided the first evidence of strongly inhibited growth of S. aureus in the presence of selenium nanoparticles after 3, 4, and 5 hours at 7.8, 15.5, and 31 μg/mL. The percentage of live bacteria also decreased in the presence of selenium nanoparticles. Therefore, this study suggests that selenium nanoparticles may be used to effectively prevent and treat S. aureus infections and thus should be further studied for such applications. PMID:21845045

  20. Rapamycin inhibits the growth of glioblastoma.

    PubMed

    Arcella, Antonietta; Biagioni, Francesca; Antonietta Oliva, Maria; Bucci, Domenico; Frati, Alessandro; Esposito, Vincenzo; Cantore, Giampaolo; Giangaspero, Felice; Fornai, Francesco

    2013-02-01

    The molecular target of rapamycin (mTOR) is up-regulated in glioblastoma (GBM) and this is associated with the rate of cell growth, stem cell proliferation and disease relapse. Rapamycin is a powerful mTOR inhibitor and strong autophagy inducer. Previous studies analyzed the effects of rapamycin in GBM cell lines. However, to our knowledge, no experiment was carried out to evaluate the effects of rapamycin neither in primary cells derived from GBM patients nor in vivo in brain GBM xenograft. These data are critical to get a deeper insight into the effects of such adjuvant therapy in GBM patients. In the present study, various doses of rapamycin were tested in primary cell cultures from GBM patients. These effects were compared with that obtained by the same doses of rapamycin in GBM cell lines (U87Mg). The effects of rapamycin were also evaluated in vivo, in brain tumors developed from mouse xenografts. Rapamycin, starting at the dose of 10nm inhibited cell growth both in U87Mg cell line and primary cell cultures derived from various GBM patients. When administered in vivo to brain xenografts in nude mice rapamycin almost doubled the survival time of mice and inhibited by more than 95% of tumor volume. PMID:23261661

  1. Effect of Algae and Plant Lectins on Planktonic Growth and Biofilm Formation in Clinically Relevant Bacteria and Yeasts

    PubMed Central

    Vasconcelos, Mayron Alves; Arruda, Francisco Vassiliepe Sousa; Carneiro, Victor Alves; Silva, Helton Colares; Nascimento, Kyria Santiago; Sampaio, Alexandre Holanda; Cavada, Benildo; Teixeira, Edson Holanda; Henriques, Mariana

    2014-01-01

    This study aimed to evaluate the abilities of plant and algae lectins to inhibit planktonic growth and biofilm formation in bacteria and yeasts. Initially, ten lectins were tested on Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella oxytoca, Pseudomonas aeruginosa, Candida albicans, and C. tropicalis at concentrations of 31.25 to 250 μg/mL. The lectins from Cratylia floribunda (CFL), Vatairea macrocarpa (VML), Bauhinia bauhinioides (BBL), Bryothamnion seaforthii (BSL), and Hypnea musciformis (HML) showed activities against at least one microorganism. Biofilm formation in the presence of the lectins was also evaluated; after 24 h of incubation with the lectins, the biofilms were analyzed by quantifying the biomass (by crystal violet staining) and by enumerating the viable cells (colony-forming units). The lectins reduced the biofilm biomass and/or the number of viable cells to differing degrees depending on the microorganism tested, demonstrating the different characteristics of the lectins. These findings indicate that the lectins tested in this study may be natural alternative antimicrobial agents; however, further studies are required to better elucidate the functional use of these proteins. PMID:24982871

  2. Effect of algae and plant lectins on planktonic growth and biofilm formation in clinically relevant bacteria and yeasts.

    PubMed

    Vasconcelos, Mayron Alves; Arruda, Francisco Vassiliepe Sousa; Carneiro, Victor Alves; Silva, Helton Colares; Nascimento, Kyria Santiago; Sampaio, Alexandre Holanda; Cavada, Benildo; Teixeira, Edson Holanda; Henriques, Mariana; Pereira, Maria Olivia

    2014-01-01

    This study aimed to evaluate the abilities of plant and algae lectins to inhibit planktonic growth and biofilm formation in bacteria and yeasts. Initially, ten lectins were tested on Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella oxytoca, Pseudomonas aeruginosa, Candida albicans, and C. tropicalis at concentrations of 31.25 to 250  μ g/mL. The lectins from Cratylia floribunda (CFL), Vatairea macrocarpa (VML), Bauhinia bauhinioides (BBL), Bryothamnion seaforthii (BSL), and Hypnea musciformis (HML) showed activities against at least one microorganism. Biofilm formation in the presence of the lectins was also evaluated; after 24 h of incubation with the lectins, the biofilms were analyzed by quantifying the biomass (by crystal violet staining) and by enumerating the viable cells (colony-forming units). The lectins reduced the biofilm biomass and/or the number of viable cells to differing degrees depending on the microorganism tested, demonstrating the different characteristics of the lectins. These findings indicate that the lectins tested in this study may be natural alternative antimicrobial agents; however, further studies are required to better elucidate the functional use of these proteins. PMID:24982871

  3. Laurenditerpenol, a New Diterpene from the Tropical Marine Alga Laurencia intricata Potently Inhibits HIF-1 Mediated Hypoxic Signaling in Breast Tumor Cells

    PubMed Central

    Mohammed, Kaleem A.; Hossain, Chowdhury Faiz; Zhang, Lei; Bruick, Richard K.; Zhou, Yu-Dong; Nagle, Dale G.

    2010-01-01

    The degree of tumor hypoxia correlates with advanced disease stages and treatment resistance. The transcription factor hypoxia-inducible factor-1 (HIF-1) promotes tumor cell adaptation and survival under hypoxic conditions. Therefore, specific HIF-1 inhibitors represent an important new class of potential tumor-selective therapeutic agents. A T47D human breast tumor cell-based reporter assay was used to examine extracts of plants and marine organisms for inhibitors of HIF-1 activation. Bioassay-guided fractionation of the lipid extract of the red alga Laurencia intricata yielded a structurally novel diterpene laurenditerpenol (1). The structure of 1 was determined spectroscopically. The relative configurations of the substituents of each ring system were assigned based on NOESY correlations. The absolute configurations of positions C-1 was determined by the modified Mosher ester procedure (directly in NMR tubes). Compound 1 potently inhibited hypoxia-activated HIF-1 (IC50: 0.4 μM) and hypoxia-induced VEGF (a potent angiogenic factor) in T47D cells. Compound 1 selectively inhibits HIF-1 activation by hypoxia but not iron chelator induced activation. Further, 1 suppresses tumor cell survival under hypoxic conditions without affecting normoxic cell growth. Compound 1 inhibits HIF-1 by blocking the induction of the oxygen-regulated HIF-1α protein. Mitochondrial respiration studies revealed that 1 suppresses oxygen consumption. PMID:15620241

  4. Growth and survival of Escherichia coli and enterococci populations in the macro-alga Cladophora (Chlorophyta)

    USGS Publications Warehouse

    Byappanahalli, M.N.; Shively, D.A.; Nevers, M.B.; Sadowsky, M.J.; Whitman, R.L.

    2003-01-01

    The macro-alga Cladophora glomerata is found in streams and lakes worldwide. High concentrations of Escherichia coli and enterococci have been reported in Cladophora along the Lake Michigan shore. The objective of this study was to determine if Cladophora supported growth of these indicator bacteria. Algal leachate readily supported in vitro multiplication of E. coli and enterococci, suggesting that leachates contain necessary growth-promoting substances. Growth was directly related to the concentration of algal leachate. E. coli survived for over 6 months in dried Cladophora stored at 4°C; residual E. coli grew after mat rehydration, reaching a carrying capacity of 8 log CFU g-1 in 48 h. Results of this study also show that the E. coli strains associated with Cladophora are highly related; in most instances they are genetically different from each other, suggesting that the relationship between E. coli and Cladophora may be casual. These findings indicate that Cladophora provides a suitable environment for indicator bacteria to persist for extended periods and to grow under natural conditions.

  5. Cell volumes, maximal growth rates of unicellular algae and ciliates, and the role of ciliates in the marine pelagial

    SciTech Connect

    Banse, K.

    1982-01-01

    A review of growth rates of diatoms and dinoflagellates in light-saturated, nutrient-replete cultures at 20/sup 0/C confirms weak dependence on cell volume or mass. These maximal (intrinsic) rates are not linearly related to surface area or surface-to-volume ratio of the cells. The growth of most diatoms is materially faster than that of dinoflagellates; other algae fall in between or below the dinoflagellates. Small ciliates have appreciably higher intrinsic growth rates than algae of the same cell volume. The average food consumption per ciliate in the marine pelagic realm is inferred to be very low, so that the realized specific growth rates are much smaller than the intrinsic potentials. Also, a previously postulated refuge from predation, afforded by small size, is extended down to about 10-..mu..m/sup 3/ cell volume.

  6. Nitric Oxide Production Inhibition and Anti-Mycobacterial Activity of Extracts and Halogenated Sesquiterpenes from the Brazilian Red Alga Laurencia Dendroidea J. Agardh

    PubMed Central

    Biá Ventura, Thatiana Lopes; da Silva Machado, Fernanda Lacerda; de Araujo, Marlon Heggdorne; de Souza Gestinari, Lísia Mônica; Kaiser, Carlos Roland; de Assis Esteves, Francisco; Lasunskaia, Elena B.; Soares, Angélica Ribeiro; Muzitano, Michelle Frazão

    2015-01-01

    Background: Red algae of the genus Laurencia J. V. Lamouroux are a rich source of secondary metabolites with important pharmacological activities such as anti-tumoral, anti-inflammatory, anti-fungal, anti-viral, anti-leishmanial, anti-helminthic, anti-malarial, anti-trypanosomal, anti-microbial as well as anti-bacterial against Mycobacterium tuberculosis. Objective: In the present study, we evaluated the inhibition of nitric oxide (NO) and tumor necrosis factor-α production and the anti-mycobacterial activity of crude extracts from the red Alga Laurencia dendroidea (from the South-Eastern coast of Brazil). Halogenated sesquiterpenes elatol (1), obtusol (2) and cartilagineol (3), previously isolated from this Alga by our group, were also studied. Materials and Methods: The lipopolysaccharide-activated macrophage cells (RAW 264.7) were used as inflammation model. Cytotoxic effect was determined using a commercial lactate dehydrogenase (LDH) kit and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The growing Mycobacterium inhibition was verified against Mycobacterium bovis Bacillus Calmette–Guérin and M. tuberculosis H37 Rv strains. Results: The crude extract from Alga collected at Angra dos Reis, RJ, Brazil, was the most active inhibitor of both mycobacterial growth (half maximal inhibitory concentration [IC50] 8.7 ± 1.4 μg/mL) and NO production by activated macrophages (IC50 5.3 ± 1.3 μg/mL). The assays with isolated compounds revealed the anti-mycobacterial activity of obtusol (2), whereas (-)-elatol (1) inhibited the release of inflammatory mediators, especially NO. To our knowledge, this is the first report describing an anti-mycobacterial effect of L. dendroidea extract and demonstrating the association of this activity with obtusol (2). Conclusion: The described effects of active compounds from L. dendroidea are promising for the control of inflammation in infectious diseases and specifically, against mycobacterial infections

  7. Hydrogen Production by the Thermophilic Alga Mastigocladus laminosus: Effects of Nitrogen, Temperature, and Inhibition of Photosynthesis

    PubMed Central

    Miyamoto, Kazuhisa; Hallenbeck, Patrick C.; Benemann, John R.

    1979-01-01

    Hydrogen production by nitrogen-limited cultures of a thermophilic blue-green alga (cyanobacterium), Mastigocladus laminosus, was studied to develop the concept of a high-temperature biophotolysis system. Biophotolytic production of hydrogen by solar radiation was also demonstrated. Hydrogen consumption activity in these cultures was relatively high and is the present limiting factor on both the net rate and duration of hydrogen production. PMID:16345432

  8. Lactam inhibiting Streptococcus mutans growth on titanium.

    PubMed

    Xavier, J G; Geremias, T C; Montero, J F D; Vahey, B R; Benfatti, C A M; Souza, J C M; Magini, R S; Pimenta, A L

    2016-11-01

    The aim of this work was to analyze the activity of novel synthetic lactams on preventing biofilm formation on titanium surfaces. Titanium (Ti6Al4V) samples were exposed to Streptococcus mutans cultures in the presence or absence of a synthetic lactam. After 48h incubation, planktonic growth was determined by spectrophotometry. Biofilm was evaluated by crystal violet staining and colony forming units (CFU·ml(-)(1)), followed by scanning electron microscopy (SEM). Results showed that the average of adhered viable cells was approximately 1.5×10(2)CFU/ml in the presence of lactam and 4×10(2)CFU/ml in its absence. This novel compound was considerable active in reducing biofilm formation over titanium surfaces, indicating its potential for the development of antimicrobial drugs targeting the inhibition of the initial stages of bacterial biofilms on dental implants abutments. PMID:27524086

  9. RESPONSES OF MARINE UNICELLULAR ALGAE TO BROMINATED ORGANIC COMPOUNDS IN SIX GROWTH MEDIA

    EPA Science Inventory

    Marine unicellular algae, Skeletonema costatum, Thalassiosira pseudonana, and Chlorella sp., were exposed to the industrial brominated compounds, tetrabromobisphenol A (TBBP), decabromobiphenyloxide (DBBO), hexabromocyclododecane (HBCD), pentabromomethylbenzene (PBMB), pentabromo...

  10. Comparison of toxicity to terrestrial plants with algal growth inhibition by herbicides

    SciTech Connect

    Garten, C.T. Jr.; Frank, M.L.

    1984-10-01

    The toxicities of 21 different herbicides to algae (Selenastrum capricornutum and Chlorella vulgaris) and to terrestrial plants (radishes, barley, and bush beans or soybeans) were compared to order to determine the feasibility of using a short-term (96-h) algal growth inhibition test for identifying chemicals having potential toxicity in a 4-week terrestrial plant bioassay. The toxicity of each test chemical, usually in combination with a commercial formulation, was evaluated at six nominal concentrations, between 0 and 100 mg/L growth medium in the algal bioassay or between 0 and 100 mg/kg substate in the terrestrial plant bioassay, in terms of both (1) the no-observed-effect concentration (NOEC), i.e., the highest concentration tested at which no significant (P < 0.05, one-sided test) reduction in algal growth rate or in terrestrial plant yield, relative to controls, was observed; and (2) the concentration at which algal growth rate or terrestrial plant yield was reduced by 50% or more relative to controls. There was generally poor agreement between results from the two types of bioassays; results from algal growth inhibition tests were not significantly correlated with results from the terrestrial plant bioassays. Overall, there was an approximately 50% chance of an algal bioassay, using Selenastrum capricornutum, successfully screening (detecting) herbicide levels that reduced terrestrial plant yield. The results indicated that algal growth inhibition tests cannot be used generically to predict phytotoxicity of herbicides to terrestrial plant species. 7 references, 14 tables.

  11. Phlorotannins from Brown Algae: inhibition of advanced glycation end products formation in high glucose induced Caenorhabditis elegans.

    PubMed

    Shakambari, Ganeshan; Ashokkumar, Balasubramaniem; Varalakshmi, Perumal

    2015-06-01

    Advanced Glycation End products (AGE) generated in a non enzymatic protein glycation process are frequently associated with diabetes, aging and other chronic diseases. Here, we explored the protective effect of phlorotannins from brown algae Padina pavonica, Sargassum polycystum and Turbinaria ornata against AGEs formation. Phlorotannins were extracted from brown algae with methanol and its purity was analyzed by TLC and RP-HPLC-DAD. Twenty five grams of P. pavonica, S. polycystum, T. ornata yielded 27.6 ± 0.8 μg/ml, 37.7 μg/ml and 37.1 ± 0.74 μg/ml of phloroglucinol equivalent of phlorotannins, respectively. Antioxidant potentials were examined through DPPH assay and their IC50 values were P. pavonica (30.12 ± 0.99 μg), S. polycystum (40.9 ± 1.2 μg) and T. ornata (22.9 ± 1.3 μg), which was comparatively lesser than the control ascorbic acid (46 ± 0.2 μg). Further, anti-AGE activity was examined in vitro by BSA-glucose assay with the extracted phlorotannins of brown algae (P. pavonica, 15.16 ± 0.26 μg/ml; S. polycystum, 35.245 ± 2.3 μg/ml; T. ornata, 22.7 ± 0.3 μg/ml), which revealed the required concentration to inhibit 50% of albumin glycation (IC50) were lower for extracts than controls (phloroglucinol, 222.33 ± 4.9 μg/ml; thiamine, 263 μg/ml). Furthermore, brown algal extracts containing phlorotannins (100 μl) exhibited protective effects against AGE formation in vivo in C. elegans with induced hyperglycemia. PMID:26155677

  12. Construction of a growth model in the green alga Tetraselmis subcordiformis using a response surface approach

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Niu, Jingyan; Liu, Jiahui; Yang, Hongshuai; Liu, Zhigang

    2016-06-01

    The green alga Tetraselmis subcordiformis has been widely used as a quality live food for aquaculture species, and also has been studied as a model organism for the photo-biological production of hydrogen. We attempted to quantify the relationship between T. subcordiformis specific growth rate (SGR) and three important environmental factors (temperature, salinity, and pH) using the central composite design and response surface method under laboratory conditions. The results showed that the linear effects of temperature and salinity were significant (P< 0.05), and they were equally important in impacting T. subcordiformis specific growth; the linear effect of pH was not significant (P>0.05); the interactive effect of temperature and pH was significant (P<0.05), whereas the temperature × salinity and salinity × pH interactions were not significant (P>0.05); all of the quadratic effects of the three factors were significant (P<0.05). A model equation for specific growth rate with the three factors was established, with the unadjusted and predictive R 2 as high as 0.990 and 0.921, respectively, suggesting that the model was a very good fit and that it could be used to predict SGR. Through optimizing the reliable model, an optimal 3-factor combination of 25 °C/35 of salinity/pH 7.9 was obtained, at which the maximum specific growth rate (0.65) was recorded, with a desirability value of 93.8%. These experimental results could serve as guidelines for increasing T. subcordiformis production efficiency.

  13. The influence of extracellular compounds produced by selected Baltic cyanobacteria, diatoms and dinoflagellates on growth of green algae Chlorella vulgaris

    NASA Astrophysics Data System (ADS)

    Żak, Adam; Kosakowska, Alicja

    2015-12-01

    Secondary metabolites produced by bacteria, fungi, algae and plants could affect the growth and development of biological and agricultural systems. This natural process that occurs worldwide is known as allelopathy. The main goal of this work was to investigate the influence of metabolites obtained from phytoplankton monocultures on the growth of green algae Chlorella vulgaris. We selected 6 species occurring in the Baltic Sea from 3 different taxonomic groups: cyanobacteria (Aphanizomenon flos-aquae; Planktothrix agardhii), diatoms (Thalassiosira pseudonana; Chaetoceros wighamii) and dinoflagellates (Alexandrium ostenfeldii; Prorocentrum minimum). In this study we have demonstrated that some of selected organisms caused allelopathic effects against microalgae. Both the negative and positive effects of collected cell-free filtrates on C. vulgaris growth, chlorophyll a concentration and fluorescence parameters (OJIP, QY, NPQ) have been observed. No evidence has been found for the impact on morphology and viability of C. vulgaris cells.

  14. Quorum Sensing Inhibition by Asparagopsis taxiformis, a Marine Macro Alga: Separation of the Compound that Interrupts Bacterial Communication

    PubMed Central

    Jha, Bhavanath; Kavita, Kumari; Westphal, Jenny; Hartmann, Anton; Schmitt-Kopplin, Philippe

    2013-01-01

    The majority of the marine algal species, though completing their life cycle in seawater, are rarely susceptible to fouling, making them an important source of quorum sensing (QS) inhibitory substances. The separation and characterization of QS inhibitors are crucial for any potential application. Thirty marine macroalgae were tested for QS inhibition activity by using Chromobacterium violaceum CV026 as the reporter strain, and among them, Asparagopsis taxiformis showed antibacterial, as well as antiquorum, sensing activities. Cinnamaldehyde (75 mM) and methanol were used as positive and negative controls, respectively. The antiquorum sensing activity of A. taxiformis was further confirmed using the sensor strain, Serratia liquefaciens MG44, having green fluorescent protein (gfp). Methanolic extract of the alga was fractionated by solid phase extraction (SPE), and each fraction was tested for QS inhibition. Two types of activities were observed—zone of clearance (antibacterial activity) and zone of inhibition with or without finger-like projections (QS inhibition). Out of five SPE cartridges, Bond Elut PH showed clear separation of these two fractions. The Ion Cyclotron Resonance Fourier Transformation Mass Spectrometer (ICR-FT/MS) analysis of the fractions further supported the bioassay results. The presence of strong QS inhibitory compound in A. taxiformis indicates its potential use in antifouling preparations. PMID:23344114

  15. Contrasting ecotoxicity effects of zinc on growth and photosynthesis in a neutrophilic alga (Chlamydomonas reinhardtii) and an extremophilic alga (Cyanidium caldarium).

    PubMed

    Mikulic, Paulina; Beardall, John

    2014-10-01

    This study aimed to determine the contrasting ecotoxicity effects of zinc on growth and photosynthesis in a neutrophilic (Chlamydomonas reinhardtii) and an extremophilic (Cyanidium caldarium) alga. Experiments were carried out to see if cells acclimated to zinc would respond differently to cells that were unexposed to zinc. The study also aimed to see if extremophiles displayed different acclimation properties to neutrophiles. Results showed that the neutrophilic alga C. reinhardtii, was more susceptible to free zinc and had a lower IC50 value than the extremophile, however its stress response protected the photosynthetic apparatus. Upon acclimation, the photosynthetic abilities of C. reinhardtii were not significantly compromised when exposed to toxic levels of free zinc. On the other hand, C. caldarium had a stress response which allowed it to tolerate significantly higher amounts of free zinc in its environment compared to C. reinhardtii , however the stress response did not protect the photosynthetic apparatus, and upon acclimation C. caldarium was no better equipped to protect its photosynthetic integrity than unexposed cells. PMID:25048933

  16. [Illumination's effect on the growth and nitrate reductase activity of typical red-tide algae in the East China Sea].

    PubMed

    Li, Hong-mei; Shi, Xiao-yong; Ding, Yan-yan; Tang, Hong-jie

    2013-09-01

    Two typical red-tide algae, Skeletonema costatum and Prorocentrum donghaiense were selected as studied objects. The nitrate reductase activity (NRA) and the growth of the two algae under different illuminations through incubation experiment were studied. The illumination condition was consistent with in situ. Results showed that P. donghaiense and S. costatum could grow normally in the solar radiation ranged from 30-60 W x m(-2), and the growth curve was "S" type. However, when solar radiation was below 9 W x m(-2), the two alga could hardly grow. In the range of 0-60 W x m(-2), three parameters (NRAmax, micro(max), Bf) increased with the increasing of light intensity, indicating that the light intensity can influence the grow of alga indirectly through influencing the nitrate reductase activity. The micro(max) and NRAmax in unite volume of Skeletonema costatum were higher than those of Prorocentrum donghaiense, indicating that Skeletonema costatum can better utilize the nitrate than Prorocentrum donghaiense. PMID:24288981

  17. Sulfated polysaccharide from the marine algae Hypnea musciformis inhibits TNBS-induced intestinal damage in rats.

    PubMed

    V Brito, Tarcisio; Barros, Francisco C N; Silva, Renan O; Dias Júnior, Genilson J; C Júnior, José Simião; Franco, Álvaro X; Soares, Pedro M G; Chaves, Luciano S; Abreu, Clara M W S; de Paula, Regina C M; Souza, Marcellus H L P; Freitas, Ana Lúcia P; R Barbosa, André Luiz

    2016-10-20

    Sulfated polysaccharides extracted from seaweed have important pharmacological properties. Thus, the aim of this study was to characterize the sulfated polysaccharide (PLS) from the algae Hypnea musciformis and evaluate its protective effect in colitis induced by trinitrobenzene sulfonic acid in rats. The sulfated polysaccharide possess a high molecular mass (1.24×10(5)gmol(-1)) and is composed of a κ-carrageenan, as depicted by FT-IR and NMR spectroscopic data. PLS was administered orally (10, 30, and 60mg/kg, p.o.) for three days, starting before TNBS (trinitrobenzene sulfonic acid) instillation (day 1). The rats were killed on day three, the portion of distal colon (5cm) was excised and evaluated macroscopic scores and wet weight. Then, samples of the intestinal were used for histological evaluation and quantification of glutathione, malonyldialdehyde acid, myeloperoxidase, nitrate/nitrite and cytokines. Our results demonstrate that PLS reduced the colitis and all analyzed biochemical parameters. Thus, we concluded that the PLS extracted from the marine algae H. musciformis reduced the colitis in animal model and may have an important promising application in the inflammatory bowel diseases. PMID:27474644

  18. Decorin: A Growth Factor Antagonist for Tumor Growth Inhibition

    PubMed Central

    Järvinen, Tero A. H.; Prince, Stuart

    2015-01-01

    Decorin (DCN) is the best characterized member of the extracellular small leucine-rich proteoglycan family present in connective tissues, typically in association with or “decorating” collagen fibrils. It has substantial interest to clinical medicine owing to its antifibrotic, anti-inflammatory, and anticancer effects. Studies on DCN knockout mice have established that a lack of DCN is permissive for tumor development and it is regarded as a tumor suppressor gene. A reduced expression or a total disappearance of DCN has been reported to take place in various forms of human cancers during tumor progression. Furthermore, when used as a therapeutic molecule, DCN has been shown to inhibit tumor progression and metastases in experimental cancer models. DCN affects the biology of various types of cancer by targeting a number of crucial signaling molecules involved in cell growth, survival, metastasis, and angiogenesis. The active sites for the neutralization of different growth factors all reside in different parts of the DCN molecule. An emerging concept that multiple proteases, especially those produced by inflammatory cells, are capable of cleaving DCN suggests that native DCN could be inactivated in a number of pathological inflammatory conditions. In this paper, we review the role of DCN in cancer. PMID:26697491

  19. Phlorotannins from brown algae (Fucus vesiculosus) inhibited the formation of advanced glycation endproducts by scavenging reactive carbonyls.

    PubMed

    Liu, Haiyan; Gu, Liwei

    2012-02-01

    Accumulation of advanced glycation end products (AGEs) in vivo is associated with aging, diabetes, Alzheimer's disease, renal failure, etc. The objective of this study was to investigate the inhibitory effects of brown algae Fucus vesiculosus phlorotannins on the formation of AGEs. F. vesiculosus phlorotannins were extracted using 70% acetone. The resultant extract was fractionated into dichloromethane, ethyl acetate, butanol, and water fractions. The ethyl acetate fraction was further fractionated into four subfractions (Ethyl-F1 to -F4) using a Sephadex LH-20 column. F. vesiculosus acetone extract or fractions significantly inhibited the formation of AGEs mediated by glucose and methylglyoxal in a concentration-dependent manner. The concentrations of F. vesiculosus extracts required to inhibit 50% of albumin glycation (EC(50)) in the bovine serum albumin (BSA)-methylglyoxal assay were lower than those of aminoguanidine (a drug candidate for diabetic complication), except for F. vesiculosus acetone extract and dichloromethane fraction. In the BSA-glucose assay, F. vesiculosus extracts inhibited BSA glycation more than or as effectively as aminoguanidine, except for Ethyl-F3 and -F4. The ethyl acetate fraction and its four subfractions scavenged more than 50% of methylglyoxal in two hours. The hypothesis whether F. vesiculosus phlorotannins scavenged reactive carbonyls by forming adducts was tested. Phloroglucinol, the constituent unit of phlorotannins, reacted with glyoxal and methylglyoxal. Five phloroglucinol-carbonyl adducts were detected and tentatively identified using HPLC-ESI-MS(n). PMID:22248148

  20. A novel alphaproteobacterial ectosymbiont promotes the growth of the hydrocarbon-rich green alga Botryococcus braunii.

    PubMed

    Tanabe, Yuuhiko; Okazaki, Yusuke; Yoshida, Masaki; Matsuura, Hiroshi; Kai, Atsushi; Shiratori, Takashi; Ishida, Ken-ichiro; Nakano, Shin-ichi; Watanabe, Makoto M

    2015-01-01

    Botryococcus braunii is a colony-forming green alga that accumulates large amounts of liquid hydrocarbons within the colony. The utilization of B. braunii for biofuel production is however hindered by its low biomass productivity. Here we describe a novel bacterial ectosymbiont (BOTRYCO-2) that confers higher biomass productivity to B. braunii. 16S rDNA analysis indicated that the sequence of BOTRYCO-2 shows low similarity (<90%) to cultured bacterial species and located BOTRYCO-2 within a phylogenetic lineage consisting of uncultured alphaproteobacterial clones. Fluorescence in situ hybridization (FISH) studies and transmission electric microscopy indicated that BOTRYCO-2 is closely associated with B. braunii colonies. Interestingly, FISH analysis of a water bloom sample also found BOTRYCO-2 bacteria in close association with cyanobacterium Microcystis aeruginosa colonies, suggesting that BOTRYCO-2 relatives have high affinity to phytoplankton colonies. A PCR survey of algal bloom samples revealed that the BOTRYCO-2 lineage is commonly found in Microcystis associated blooms. Growth experiments indicated that B. braunii Ba10 can grow faster and has a higher biomass (1.8-fold) and hydrocarbon (1.5-fold) yield in the presence of BOTRYCO-2. Additionally, BOTRYCO-2 conferred a higher biomass yield to BOT-22, one of the fastest growing strains of B. braunii. We propose the species name 'Candidatus Phycosocius bacilliformis' for BOTRYCO-2. PMID:26130609

  1. Use of prolines for improving growth and other properties of plants and algae

    DOEpatents

    Unkefer, Pat J.; Knight, Thomas J.; Martinez, Rodolfo A.

    2004-12-14

    Increasing the concentration of prolines, such as 2-hydroxy-5-oxoproline, in the foliar portions of plants has been shown to cause an increase in carbon dioxide fixation, growth rate, dry weight, nutritional value (amino acids), nodulation and nitrogen fixation, photosynthetically derived chemical energy, and resistance to insect pests over the same properties for wild type plants. This can be accomplished in four ways: (1) the application of a solution of the proline directly to the foliar portions of the plant by spraying these portions; (2) applying a solution of the proline to the plant roots; (3) genetically engineering the plant and screening to produce lines that over-express glutamine synthetase in the leaves which gives rise to increased concentration of the metabolite, 2-hydroxy-5-oxoproline (this proline is also known as 2-oxoglutaramate); and (4) impairing the glutamine synthetase activity in the plant roots which causes increased glutamine synthetase activity in the leaves which gives rise to increased concentration of 2-hydroxy-5-oxoproline. Prolines have also been found to induce similar effects in algae.

  2. Use of prolines for improving growth and other properties of plants and algae

    DOEpatents

    Unkefer, Pat J.; Knight, Thomas J.; Martinez, Rodolfo A.

    2003-04-29

    Increasing the concentration of prolines such as 2-hydroxy-5-oxoproline, in the foliar portions of plants has been shown to cause an increase in carbon dioxide fixation, growth rate, dry weight, nutritional value (amino acids), nodulation and nitrogen fixation, photosynthetically derived chemical energy, and resistance to insect pests over the same properties for wild type plants. This can be accomplished in four ways: (1) the application of a solution of the proline directly to the foliar portions of the plant by spraying these portions; (2) applying a solution of the proline to the plant roots; (3) genetically engineering the plant and screening to produce lines that overexpress glutamine synthetase in the leaves which gives rise to increased concentration of the metabolite, 2-hydroxy-5-oxoproline (this proline is also known as 2-oxoglutaramnate); and (4) impairing the glutamine synthetase activity in the plant roots which causes increased glutamine synthetase activity in the leaves which gives rise to increased concentration of 2-hydroxy-5-oxoproline. Prolines have also been found to induce similar effects in algae.

  3. Use of prolines for improving growth and other properties of plants and algae

    DOEpatents

    Unkefer, Pat J.; Knight, Thomas J.; Martinez, Rodolfo A.

    2003-07-15

    Increasing the concentration of prolines, such as 2-hydroxy-5-oxoproline, in the foliar portions of plants has been shown to cause an increase in carbon dioxide fixation, growth rate, dry weight, nutritional value (amino acids), nodulation and nitrogen fixation, photosynthetically derived chemical energy, and resistance to insect pests over the same properties for wild type plants. This can be accomplished in four ways: (1) the application of a solution of the proline directly to the foliar portions of the plant by spraying these portions; (2) applying a solution of the proline to the plant roots; (3) genetically engineering the plant and screening to produce lines that over-express glutamine synthetase in the leaves which gives rise to increased concentration of the metabolite, 2-hydroxy-5-oxoproline (this proline is also known as 2-oxoglutaramate); and (4) impairing the glutamine synthetase activity in the plant roots which causes increased glutamine synthetase activity in the leaves which gives rise to increased concentration of 2-hydroxy-5-oxoproline. Prolines have also been found to induce similar effects in algae.

  4. A novel alphaproteobacterial ectosymbiont promotes the growth of the hydrocarbon-rich green alga Botryococcus braunii

    PubMed Central

    Tanabe, Yuuhiko; Okazaki, Yusuke; Yoshida, Masaki; Matsuura, Hiroshi; Kai, Atsushi; Shiratori, Takashi; Ishida, Ken-ichiro; Nakano, Shin-ichi; Watanabe, Makoto M.

    2015-01-01

    Botryococcus braunii is a colony-forming green alga that accumulates large amounts of liquid hydrocarbons within the colony. The utilization of B. braunii for biofuel production is however hindered by its low biomass productivity. Here we describe a novel bacterial ectosymbiont (BOTRYCO-2) that confers higher biomass productivity to B. braunii. 16S rDNA analysis indicated that the sequence of BOTRYCO-2 shows low similarity (<90%) to cultured bacterial species and located BOTRYCO-2 within a phylogenetic lineage consisting of uncultured alphaproteobacterial clones. Fluorescence in situ hybridization (FISH) studies and transmission electric microscopy indicated that BOTRYCO-2 is closely associated with B. braunii colonies. Interestingly, FISH analysis of a water bloom sample also found BOTRYCO-2 bacteria in close association with cyanobacterium Microcystis aeruginosa colonies, suggesting that BOTRYCO-2 relatives have high affinity to phytoplankton colonies. A PCR survey of algal bloom samples revealed that the BOTRYCO-2 lineage is commonly found in Microcystis associated blooms. Growth experiments indicated that B. braunii Ba10 can grow faster and has a higher biomass (1.8-fold) and hydrocarbon (1.5-fold) yield in the presence of BOTRYCO-2. Additionally, BOTRYCO-2 conferred a higher biomass yield to BOT-22, one of the fastest growing strains of B. braunii. We propose the species name ‘Candidatus Phycosocius bacilliformis’ for BOTRYCO-2. PMID:26130609

  5. PDZ-binding kinase/T-LAK cell-originated protein kinase is a target of the fucoidan from brown alga Fucus evanescens in the prevention of EGF-induced neoplastic cell transformation and colon cancer growth

    PubMed Central

    Wang, Zhe; Ermakova, Svetlana P.; Xiao, JuanJuan; Lu, Tao; Xue, PeiPei; Zvyagintseva, Tatyana N.; Xiong, Hua; Shao, Chen; Yan, Wei; Duan, Qiuhong; Zhu, Feng

    2016-01-01

    The fucoidan with high anticancer activity was isolated from brown alga Fucus evanescens. The compound effectively prevented EGF-induced neoplastic cell transformation through inhibition of TOPK/ERK1/2/MSK 1 signaling axis. In vitro studies showed that the fucoidan attenuated mitogen-activated protein kinases downstream signaling in a colon cancer cells with different expression level of TOPK, resulting in growth inhibition. The fucoidan exerts its effects by directly interacting with TOPK kinase in vitro and ex vivo and inhibits its kinase activity. In xenograft animal model, oral administration of the fucoidan suppressed HCT 116 colon tumor growth. The phosphorylation of TOPK downstream signaling molecules in tumor tissues was also inhibited by the fucoidan. Taken together, our findings support the cancer preventive efficacy of the fucoidan through its targeting of TOPK for the prevention of neoplastic cell transformation and progression of colon carcinomas in vitro and ex vivo. PMID:26936995

  6. Spirulan from blue-green algae inhibits fibrin and blood clots: its potent antithrombotic effects.

    PubMed

    Choi, Jun-Hui; Kim, Seung; Kim, Sung-Jun

    2015-05-01

    We investigated in vitro and in vivo fibrinolytic and antithrombotic activity of spirulan and analyzed its partial biochemical properties. Spirulan, a sulfated polysaccharide from the blue-green alga Arthrospira platensis, exhibits antithrombotic potency. Spirulan showed a strong fibrin zymogram lysis band corresponding to its molecular mass. It specifically cleaved Aα and Bβ, the major chains of fibrinogen. Spirulan directly decreased the activity of thrombin and factor X activated (FXa), procoagulant proteins. In vitro assays using human fibrin and mouse blood clots showed fibrinolytic and hemolytic activities of spirulan. Spirulan (2 mg/kg) showed antithrombotic effects in the ferric chloride (FeCl3 )-induced carotid arterial thrombus model and collagen and epinephrine-induced pulmonary thromboembolism mouse model. These results may be attributable to the prevention of thrombus formation and partial lysis of thrombus. Therefore, we suggest that spirulan may be a potential antithrombotic agent for thrombosis-related diseases. PMID:25651404

  7. Dynamics of Metal Partitioning at the Cell-Solution Interface: Implications for Toxicity Assessment under Growth-Inhibiting Conditions.

    PubMed

    Duval, Jérôme F L; Paquet, Nathalie; Lavoie, Michel; Fortin, Claude

    2015-06-01

    Metal toxicity toward microorganisms is usually evaluated by determining growth inhibition. To achieve a mechanistic interpretation of such toxic effects, the intricate coupling between cell growth kinetics and metal partitioning dynamics at the cell-solution interface over time must be considered on a quantitative level. A formalism is elaborated to evaluate cell-surface-bound, internalized, and extracellular metal fractions in the limit where metal uptake kinetics is controlled by internalization under noncomplexing medium conditions. Cell growth kinetics is tackled using the continuous logistic equation modified to include growth inhibition by metal accumulation to intracellular or cell surface sites. The theory further includes metal-proton competition for adsorption at cell-surface binding sites, as well as possible variation of cell size during exposure to metal ions. The formalism elucidates the dramatic impacts of initial cell concentration on metal bioavailability and toxicity over time, in agreement with reported algae bioassays. It further highlights that appropriate definition of toxicity endpoints requires careful inspection of the ratio between exposure time scale and time scale of metal depletion from bulk solution. The latter depends on metal internalization-excretion rate constants, microorganism growth, and the extent of metal adsorption on nonspecific, transporter, and growth inhibitory sites. As an application of the theory, Cd toxicity in the algae Pseudokirchneriella subcapitata is interpreted from constrained modeling of cell growth kinetics and of interfacial Cd-partitioning dynamics measured under various exposure conditions. PMID:25945520

  8. Potential use of duckweed based anaerobic digester effluent as a feed source for heterotrophic growth of micro-algae

    NASA Astrophysics Data System (ADS)

    Ahmadi, L.; Dupont, R.

    2013-12-01

    Finding an alternative source of energy for the growing world's demand is a challenging task being considered by many scientists. Various types of renewable energy alternatives are being investigated by researchers around the world. The abundance of duckweed (i.e., Lemna and Wolfia sp.) in wetlands and wastewater lagoons, their rapid growth, and their capacity for nutrient, metal and other contaminant removal from wastewater suggests their potential as an inexpensive source of biomass for biofuel production. Another source of biomass for biofuel and energy production is micro-algae. The large-scale growth of micro-algae can potentially be achieved in a smaller footprint and at a higher rate and lower cost via heterotrophic growth compared to autotrophic growth for specific species that can grow under both conditions. Here we describe two types of research. First, two lab-scale, 5 L anaerobic digesters containing municipal raw wastewater that were set up, maintained and monitored over the course of 6 months using duckweed as the feed source. The pH, salinity, amount of gas production and gas composition were measured on a daily basis. The results from these measurements show that duckweed can be used as a good source of biofuel production in the form of methane gas. The second set of reactors consisted of two 1 L batch fed reactors containing algae (Chlorella vulgaris) grown in the lab environment heterotrophically. The pH and DO were monitored on a daily basis in order to investigate their effect on algae growth. Lipid analysis of the harvested algal biomass was done to investigate the efficiency of harvestable biofuel products. A nutrient solution containing glucose as an energy source was used as the initial feed solution, and the potential substitution of the glucose solution with the organic carbon residue from the duckweed digester effluent was investigated. Methane production, carbon stabilization, and gas composition results from the duckweed fed anaerobic

  9. The impact of supplementing lambs with algae on growth, meat traits and oxidative status.

    PubMed

    Hopkins, D L; Clayton, E H; Lamb, T A; van de Ven, R J; Refshauge, G; Kerr, M J; Bailes, K; Lewandowski, P; Ponnampalam, E N

    2014-10-01

    The current study examined the effect of supplementing lambs with algae. Forty, three month old lambs were allocated to receive a control ration based on oats and lupins (n=20) or the control ration with DHA-Gold™ algae (~2% of the ration, n=20). These lambs came from dams previously fed a ration based on either silage (high in omega-3) or oats and cottonseed meal (OCSM: high in omega-6) at joining (dam nutrition, DN). Lamb performance, carcase weight and GR fat content were not affected by treatment diet (control vs algae) or DN (silage vs OSCM). Health claimable omega-3 fatty acids (EPA+DHA) were significantly greater in the LL of lambs fed algae (125±6mg/100g meat) compared to those not fed algae (43±6mg/100g meat) and this effect was mediated by DN. Supplementing with algae high in DHA provides a means of improving an aspect of the health status of lamb meat. PMID:24950082

  10. Bioactivity of Benthic and Picoplanktonic Estuarine Cyanobacteria on Growth of Photoautotrophs: Inhibition versus Stimulation

    PubMed Central

    Lopes, Viviana R.; Vasconcelos, Vitor M.

    2011-01-01

    Understanding potential biochemical interactions and effects among cyanobacteria and other organisms is one of the main keys to a better knowledge of microbial population structuring and dynamics. In this study, the effects of cyanobacteria from benthos and plankton of estuaries on other cyanobacteria and green algae growth were evaluated. To understand how the estuarine cyanobacteria might influence the dynamics of phytoplankton, experiments were carried out with the freshwater species Microcystis aeruginosa and Chlorella sp., and the marine Synechocystis salina and Nannochloropsis sp. exposed to aqueous and organic (70% methanol) crude extracts of cyanobacteria for 96 h. The most pronounced effect observed was the growth stimulation. Growth inhibition was also observed for S. salina and M. aeruginosa target-species at the highest and lowest concentrations of cyanobacterial extracts. The methanolic crude extract of Phormidium cf. chalybeum LEGE06078 was effective against S. salina growth in a concentration-dependent manner after 96 h-exposure. All of the cyanobacterial isolates showed some bioactivity on the target-species growth, i.e., inhibitory or stimulating effects. These results indicate that the analyzed cyanobacterial isolates can potentially contribute to blooms’ proliferation of other cyanobacteria and to the abnormal growth of green algae disturbing the dynamic of estuarine phytoplankton communities. Since estuaries are transitional ecosystems, the benthic and picoplanktonic estuarine cyanobacteria can change both freshwater and marine phytoplankton succession, competition and bloom formation. Furthermore, a potential biotechnological application of these isolates as a tool to control cyanobacteria and microalgae proliferation can be feasible. This work is the first on the subject of growth responses of photoautotrophs to cyanobacteria from Atlantic estuarine environments. PMID:21673889

  11. Profiling of lipid and glycogen accumulations under different growth conditions in the sulfothermophilic red alga Galdieria sulphuraria.

    PubMed

    Sakurai, Toshihiro; Aoki, Motohide; Ju, Xiaohui; Ueda, Tatsuya; Nakamura, Yasunori; Fujiwara, Shoko; Umemura, Tomonari; Tsuzuki, Mikio; Minoda, Ayumi

    2016-01-01

    The unicellular red alga Galdieria sulphuraria grows efficiently and produces a large amount of biomass in acidic conditions at high temperatures. It has great potential to produce biofuels and other beneficial compounds without becoming contaminated with other organisms. In G. sulphuraria, biomass measurements and glycogen and lipid analyses demonstrated that the amounts and compositions of glycogen and lipids differed when cells were grown under autotrophic, mixotrophic, and heterotrophic conditions. Maximum biomass production was obtained in the mixotrophic culture. High amounts of glycogen were obtained in the mixotrophic cultures, while the amounts of neutral lipids were similar between mixotrophic and heterotrophic cultures. The amounts of neutral lipids were highest in red algae, including thermophiles. Glycogen structure and fatty acids compositions largely depended on the growth conditions. PMID:26595665

  12. Bee venom inhibits growth of human cervical tumors in mice.

    PubMed

    Lee, Hye Lim; Park, Sang Ho; Kim, Tae Myoung; Jung, Yu Yeon; Park, Mi Hee; Oh, Sang Hyun; Yun, Hye Seok; Jun, Hyung Ok; Yoo, Hwan Soo; Han, Sang-Bae; Lee, Ung Soo; Yoon, Joo Hee; Song, Min Jong; Hong, Jin Tae

    2015-03-30

    We studied whether bee venom (BV) inhibits cervical tumor growth through enhancement of death receptor (DR) expressions and inactivation of nuclear factor kappa B (NF-κB) in mice. In vivo study showed that BV (1 mg/kg) inhibited tumor growth. Similar inhibitory effects of BV on cancer growth in primary human cervical cancer cells were also found. BV (1-5 μg/ml) also inhibited the growth of cancer cells, Ca Ski and C33Aby the induction of apoptotic cell death in a dose dependent manner. Agreed with cancer cell growth inhibition, expression of death receptors; FAS, DR3 and DR6, and DR downstream pro-apoptotic proteins including caspase-3 and Bax was concomitantly increased, but the NF-κB activity and the expression of Bcl-2 were inhibited by treatment with BV in tumor mice, human cancer cell and human tumor samples as well as cultured cancer cells. In addition, deletion of FAS, DR3 and DR6 by small interfering RNA significantly reversed BV-induced cell growth inhibitory effects as well as NF-κB inactivation. These results suggest that BV inhibits cervical tumor growth through enhancement of FAS, DR3 and DR6 expression via inhibition of NF-κB pathway. PMID:25730901

  13. Blue-Green Algae Inhibit the Development of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice.

    PubMed

    Ku, Chai Siah; Kim, Bohkyung; Pham, Tho X; Yang, Yue; Wegner, Casey J; Park, Young-Ki; Balunas, Marcy; Lee, Ji-Young

    2015-12-01

    Hyperlipidemia and inflammation contribute to the development of atherosclerotic lesions. Our objective was to determine antiatherogenic effect of edible blue-green algae (BGA) species, that is, Nostoc commune var. sphaeroides Kützing (NO) and Spirulina platensis (SP), in apolipoprotein E knockout (ApoE(-/-)) mice, a well-established mouse model of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat/high-cholesterol (HF/HC, 15% fat and 0.2% cholesterol by wt) control diet or a HF/HC diet supplemented with 5% (w/w) of NO or SP powder for 12 weeks. Plasma total cholesterol (TC) and triglycerides (TG) were measured, and livers were analyzed for histology and gene expression. Morphometric analysis for lesions and immunohistochemical analysis for CD68 were conducted in the aorta and the aortic root. NO supplementation significantly decreased plasma TC and TG, and liver TC, compared to control and SP groups. In the livers of NO-fed mice, less lipid droplets were present with a concomitant decrease in fatty acid synthase protein levels than the other groups. There was a significant increase in hepatic low-density lipoprotein receptor protein levels in SP-supplemented mice than in control and NO groups. Quantification of aortic lesions by en face analysis demonstrated that both NO and SP decreased aortic lesion development to a similar degree compared with control. While lesions in the aortic root were not significantly different between groups, the CD68-stained area in the aortic root was significantly lowered in BGA-fed mice than controls. In conclusion, both NO and SP supplementation decreased the development of atherosclerotic lesions, suggesting that they may be used as a natural product for atheroprotection. PMID:26566121

  14. Synergy between angiostatin and endostatin: inhibition of ovarian cancer growth.

    PubMed

    Yokoyama, Y; Dhanabal, M; Griffioen, A W; Sukhatme, V P; Ramakrishnan, S

    2000-04-15

    Ovarian cancer is the leading cause of fatality among gynecological malignancies. Ovarian cancer growth is angiogenesis-dependent, and an increased production of angiogenic growth factors such as vascular endothelial growth factor is prognostically significant even during early stages of the disease. Therefore, we investigated whether antiangiogenic treatment can be used to inhibit the growth of ovarian cancer in an experimental model system. Mouse angiostatin (kringle 1-4) and endostatin were expressed in yeast. Purified angiostatin and endostatin were then used to treat established ovarian cancers in athymic mice. These studies showed that both angiostatin and endostatin inhibited tumor growth. However, angiostatin treatment was more effective in inhibiting ovarian cancer growth when compared with endostatin in parallel experiments. Residual tumors obtained from angiostatin- and endostatin-treated animals showed decreased number of blood vessels and, as a consequence, increased apoptosis of tumor cells. Subsequently, the efficacy of a combined treatment with angiostatin and endostatin was investigated. In the presence of both angiostatic proteins, endothelial cell proliferation was synergistically inhibited. Similarly, a combination regimen using equal amounts of angiostatin and endostatin showed more than additive effect in tumor growth inhibition when compared with treatment with individual angiostatic protein. These studies demonstrate synergism between two angiostatic molecules and that antiangiogenic therapy can be used to inhibit ovarian cancer growth. PMID:10786683

  15. Calcite crystal growth rate inhibition by polycarboxylic acids

    USGS Publications Warehouse

    Reddy, M.M.; Hoch, A.R.

    2001-01-01

    Calcite crystal growth rates measured in the presence of several polycarboxyclic acids show that tetrahydrofurantetracarboxylic acid (THFTCA) and cyclopentanetetracarboxylic acid (CPTCA) are effective growth rate inhibitors at low solution concentrations (0.01 to 1 mg/L). In contrast, linear polycarbocylic acids (citric acid and tricarballylic acid) had no inhibiting effect on calcite growth rates at concentrations up to 10 mg/L. Calcite crystal growth rate inhibition by cyclic polycarboxyclic acids appears to involve blockage of crystal growth sites on the mineral surface by several carboxylate groups. Growth morphology varied for growth in the absence and in the presence of both THFTCA and CPTCA. More effective growth rate reduction by CPTCA relative to THFTCA suggests that inhibitor carboxylate stereochemical orientation controls calcite surface interaction with carboxylate inhibitors. ?? 20O1 Academic Press.

  16. Streptomycin affects the growth and photochemical activity of the alga Chlorella vulgaris.

    PubMed

    Perales-Vela, Hugo Virgilio; García, Roberto Velasco; Gómez-Juárez, Evelyn Alicia; Salcedo-Álvarez, Martha Ofelia; Cañizares-Villanueva, Rosa Olivia

    2016-10-01

    Antibiotics are increasingly being used in human and veterinary medicine, as well as pest control in agriculture. Recently, their emergence in the aquatic environment has become a global concern. The aim of this study was to evaluate the effect of streptomycin on growth and photosynthetic activity of Chlorella vulgaris after 72h exposure. We found that growth, photosynthetic activity and the content of the D1 protein of photosystem II decreased. Analysis of chlorophyll a fluorescence emission shows a reduction in the energy transfer between the antenna complex and reaction center. Also the activity of the oxygen evolution complex and electron flow between QA and QB were significantly reduced; in contrast, we found an increase in the reduction rate of the acceptor side of photosystem I. The foregoing can be attributed to the inhibition of the synthesis of the D1 protein and perhaps other coded chloroplast proteins that are part of the electron transport chain which are essential for the transformation of solar energy in the photosystems. We conclude that micromolar concentrations of streptomycin can affect growth and photosynthetic activity of Chlorella vulgaris. The accumulation of antibiotics in the environment can become an ecological problem for primary producers in the aquatic environment. PMID:27344399

  17. Anti-photoaging activity and inhibition of matrix metalloproteinase (MMP) by marine red alga, Corallina pilulifera methanol extract

    NASA Astrophysics Data System (ADS)

    Ryu, BoMi; Qian, Zhong-Ji; Kim, Moon-Moo; Nam, Ki Wan; Kim, Se-Kwon

    2009-02-01

    Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by UV-irradiation-associated generation of reactive oxygen species (ROS). In this study, the alga Corallina pilulifera methanol (CPM) extract has been shown to exert a potent antioxidant activity and protective effect on UVA-induced oxidative stress of human dermal fibroblast (HDF) cell. Antioxidant evaluated by various antioxidant assays. These include reducing power, total antioxidant, DPPH radical scavenging, hydroxyl radical scavenging and protective effect on DNA damage caused by hydroxyl radicals generated. Further, the ROS level was detected using a fluorescence probe, 2',7'-dichlorofluorescein diacetate (DCFH-DA), which could be converted to highly fluorescent dichlorofluorescein (DCF) with the presence of intracellular ROS on HT-1080 cells. Those various antioxidant activities were compared to standard antioxidants such as α-tocopherol. In addition, the in vitro activities of MMP-2 and MMP-9 in HDF cell were inhibited by C. pilulifera methanol extract dose dependently by using gelatin zymography method. The results obtained in the present study suggested that the C. pilulifera methanol extract may be a potential source of natural anti-photoaging.

  18. Mechanisms of suberoylanilide hydroxamic acid inhibition of mammary cell growth

    PubMed Central

    Said, Thenaa K; Moraes, Ricardo CB; Sinha, Raghu; Medina, Daniel

    2001-01-01

    The mechanism of suberoylanilide hydroxamic acid in cell growth inhibition involved induction of pRb-2/p130 interaction and nuclear translocation with E2F-4, followed by significant repression in E2F-1 and PCNA nuclear levels, which led to inhibition in DNA synthesis in mammary epithelial cell lines. PMID:11250759

  19. Promotive effect of se on the growth and antioxidation of a blue-green alga Spirulina maxima

    NASA Astrophysics Data System (ADS)

    Zhi-Gang, Zhou; Zhi-Li, Liu

    1998-12-01

    Cultures of a blue-green alga Spirulina maxima (Setch. et Gard.) Geitler with various concentrations of Se in Zarrouk's medium showed that not higher than 40 mg/L Se could promote its growth. The present experiments showed that S. maxima grown under normal conditions, has an oxidant stress defence system for hydrogen peroxide (H2O2) removal, which is the Halliwell-Asada pathway. When 4 to 20 mg/L Se was added to the algal medium, this pathway was replaced by a so-called Sestressed pathway containing GSH peroxidase (GSH-POD). As a result of the occurrence of both higher activity of GSH-POD and lower levels of hydroxyl radical (OH·), the Se-stressed pathway scavenged H2O2 so effectively that the growth of S. maxima was promoted by 4 to 20 mg/L Se. While GSH-POD activity of the alga disappeared at 40 mg/L Se, the recovery of ascorbate peroxidase was observed. The lower levels of ascorbic acid and GSH made the Halliwell-Asada pathway for scavenging H2O2 less effective, while the highest activity of catalase might be responsible in part for the H2O2 removal, causing the level of OH· in S. maxima grown at 40 mg/L Se to be much higher than the OH· level in this alga grown at 4 to 20 mg/L Se, but lower than that in the control. The OH· level changes caused the growth of S. maxima cultured at 40 mg/L Se to increase slightly to close to that of the control.

  20. Inhibition of angiogenesis and murine tumour growth by laminarin sulphate.

    PubMed Central

    Hoffman, R.; Paper, D. H.; Donaldson, J.; Vogl, H.

    1996-01-01

    LAM S5 is a polysulphated derivative of the glucan laminarian that inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells. This report demonstrates that LAM S5 has anti-angiogenic activity, as shown by inhibition of tubule formation by endothelial cells cultured on Matrigel and inhibition of vascularisation of the chick chorioallantoic membrane. In addition, LAM S5 caused a tumour growth delay of the murine RIF-1 tumour of 2.6 days (P = 0.01). Images Figure 2 PMID:8630276

  1. Endocannabinoids Inhibit the Growth of Free-Living Amoebae▿

    PubMed Central

    Dey, Rafik; Pernin, Pierre; Bodennec, Jacques

    2010-01-01

    The cannabinoid Δ9-tetrahydrocannabinol inhibits the growth of some pathogenic amoebae in vitro and exacerbates amoebic encephalitis in animal models. However, the effects of endogenous cannabinoids on amoebae remain unknown. Therefore, we tested several endocannabinoids (N-acyl ethanolamines and 2-O-acyl glycerol) on different genera of amoebae. The results showed that all of the endocannabinoids tested inhibit amoebic growth at subpharmacological doses, with 50% inhibitory concentrations ranging from 15 to 20 μM. A nonhydrolyzable endocannabinoid had similar effects, showing that the inhibition seen results from endocannabinoids per se rather than from a catabolic product. PMID:20479202

  2. Endocannabinoids inhibit the growth of free-living amoebae.

    PubMed

    Dey, Rafik; Pernin, Pierre; Bodennec, Jacques

    2010-07-01

    The cannabinoid Delta(9)-tetrahydrocannabinol inhibits the growth of some pathogenic amoebae in vitro and exacerbates amoebic encephalitis in animal models. However, the effects of endogenous cannabinoids on amoebae remain unknown. Therefore, we tested several endocannabinoids (N-acyl ethanolamines and 2-O-acyl glycerol) on different genera of amoebae. The results showed that all of the endocannabinoids tested inhibit amoebic growth at subpharmacological doses, with 50% inhibitory concentrations ranging from 15 to 20 microM. A nonhydrolyzable endocannabinoid had similar effects, showing that the inhibition seen results from endocannabinoids per se rather than from a catabolic product. PMID:20479202

  3. Transgenic algae engineered for higher performance

    DOEpatents

    Unkefer, Pat J; Anderson, Penelope S; Knight, Thomas J

    2014-10-21

    The present disclosure relates to transgenic algae having increased growth characteristics, and methods of increasing growth characteristics of algae. In particular, the disclosure relates to transgenic algae comprising a glutamine phenylpyruvate transaminase transgene and to transgenic algae comprising a glutamine phenylpyruvate transaminase transgene and a glutamine synthetase.

  4. Timing of growth inhibition following shoot inversion in Pharbitis nil

    NASA Technical Reports Server (NTRS)

    Abdel-Rahman, A. M.; Cline, M. G.

    1989-01-01

    Shoot inversion in Pharbitis nil results in the enhancement of ethylene production and in the inhibition of elongation in the growth zone of the inverted shoot. The initial increase in ethylene production previously was detected within 2 to 2.75 hours after inversion. In the present study, the initial inhibition of shoot elongation was detected within 1.5 to 4 hours with a weighted mean of 2.4 hours. Ethylene treatment of upright shoots inhibited elongation in 1.5 hours. A cause and effect relationship between shoot inversion-enhanced ethylene production and inhibition of elongation cannot be excluded.

  5. Inhibition of rate of tumor growth by creatine and cyclocreatine.

    PubMed Central

    Miller, E E; Evans, A E; Cohn, M

    1993-01-01

    Growth rate inhibition of subcutaneously implanted tumors results from feeding rats and athymic nude mice diets containing 1% cyclocreatine or 1%, 2%, 5%, or 10% creatine. The tumors studied included rat mammary tumors (Ac33tc in Lewis female rats and 13762A in Fischer 344 female rats), rat sarcoma MCI in Lewis male rats, and tumors resulting from the injection of two human neuroblastoma cell lines, IMR-5 and CHP-134, in athymic nude mice. Inhibition was observed regardless of the time experimental diets were administered, either at the time of tumor implantation or after the appearance of palpable tumors. For mammary tumor Ac33tc, the growth inhibition during 24 days after the implantation was approximately 50% for both 1% cyclocreatine and 1% creatine, and inhibition increased as creatine was increased from 2% to 10% of the diet. For the other rat mammary tumor (13762A), there was approximately 35% inhibition by both 1% cyclocreatine and 2% creatine. In the case of the MCI sarcoma, the inhibitory effect appeared more pronounced at earlier periods of growth, ranging from 26% to 41% for 1% cyclocreatine and from 30% to 53% for 1% creatine; there was no significant difference in growth rate between the tumors in the rats fed 1% and 5% creatine. The growth rate of tumors in athymic nude mice, produced by implantation of the human neuroblastoma IMR-5 cell line, appeared somewhat more effectively inhibited by 1% cyclocreatine than by 1% creatine, and 5% creatine feeding was most effective. For the CHP-134 cell line, 33% inhibition was observed for the 1% cyclocreatine diet and 71% for the 5% creatine diet. In several experiments, a delay in appearance of tumors was observed in animals on the experimental diets. In occasional experiments, neither additive inhibited tumor growth rate for the rat tumors or the athymic mouse tumors. Images Fig. 3 PMID:8475072

  6. Ozone selectively inhibits growth of human cancer cells

    SciTech Connect

    Sweet, F.; Kao, M.S.; Lee, S.C.; Hagar, W.L.; Sweet, W.E.

    1980-08-01

    The growth of human cancer cells from lung, breast, and uterine tumors was selectively inhibited in a dose-dependent manner by ozone at 0.3 to 0.8 part per million of ozone in ambient air during 8 days of culture. Human lung diploid fibroblasts served as noncancerous control cells. The presence of ozone at 0.3 to 0.5 part per million inhibited cancer cell growth 40 and 60 percent, respectively. The noncancerous lung cells were unaffected at these levels. Exposure to ozone at 0.8 part per million inhibited cancer cell growth more than 90 percent and control cell growth less than 50 percent. Evidently, the mechanisms for defense against ozone damage are impaired in human cancer cells.

  7. Mullerian inhibiting substance inhibits ovarian cell growth through an Rb-independent mechanism.

    PubMed

    Ha, T U; Segev, D L; Barbie, D; Masiakos, P T; Tran, T T; Dombkowski, D; Glander, M; Clarke, T R; Lorenzo, H K; Donahoe, P K; Maheswaran, S

    2000-11-24

    Müllerian inhibiting substance (MIS), a transforming growth factor-beta family member, causes regression of the Müllerian duct in male embryos. MIS overexpression in transgenic mice ablates the ovary, and MIS inhibits the growth of ovarian cancer cell lines in vitro, suggesting a key role for this hormone in postnatal development of the ovary. This report describes a mechanism for MIS-mediated growth inhibition in both a human epithelial ovarian cancer cell line and a cell line derived from normal ovarian surface epithelium, which is the origin of human epithelial ovarian cancers. MIS-treated cells accumulated in the G(1) phase of the cell cycle and subsequently underwent apoptosis. MIS up-regulated the cyclin-dependent kinase inhibitor p16 through an MIS type II receptor-mediated mechanism and inhibited growth in the absence of detectable or inactive Rb protein. Prolonged treatment with MIS down-regulated the Rb-related protein p130 and increased the Rb family-regulated transcription factor E2F1, overexpression of which inhibited growth. These findings demonstrate that p16 is required for MIS-mediated growth inhibition in ovarian epithelial cells and tumor cells and suggest that up-regulation of E2F1 also plays a role in this process. PMID:10958795

  8. Growth of the green algae Chlamydomonas reinhardtii under red and blue lasers

    NASA Astrophysics Data System (ADS)

    Kuwahara, Sara S.; Cuello, Joel L.; Myhre, Graham; Pau, Stanley

    2011-03-01

    Red and blue lasers, holding promise as an electric light source for photosynthetic systems on account of being true monochromatic, high-power, and having high electrical-conversion efficiency, were employed in growing a green alga, Chlamydomonas reinhardtii. The laser treatments tested included: 655-nm Red; 680-nm Red; 655-nm Red+474-nm Blue and 680-nm Red+474-nm Blue. A white cold cathode lamp with spectral output similar to that of white fluorescent lamp served as control. C. reinhardtii successfully grew and divided under the 655 and 680-nm red lasers as well as under the white-light control. Supplementing either red with blue laser, however, resulted in increased algae cell count that significantly exceeded those under both red lasers and the white-light control on average by 241%.

  9. Consistent fractionation of 13C in nature and in the laboratory: growth-rate effects in some haptophyte algae.

    PubMed

    Bidigare, R R; Fluegge, A; Freeman, K H; Hanson, K L; Hayes, J M; Hollander, D; Jasper, J P; King, L L; Laws, E A; Milder, J; Millero, F J; Pancost, R; Popp, B N; Steinberg, P A; Wakeham, S G

    1997-06-01

    The carbon isotopic fractionation accompanying formation of biomass by alkenone-producing algae in natural marine environments varies systematically with the concentration of dissolved phosphate. Specifically, if the fractionation is expressed by epsilon p approximately delta e - delta p, where delta e and delta p are the delta 13C values for dissolved CO2 and for algal biomass (determined by isotopic analysis of C37 alkadienones), respectively, and if Ce is the concentration of dissolved CO2, micromole kg-1, then b = 38 + 160*[PO4], where [PO4] is the concentration of dissolved phosphate, microM, and b = (25 - epsilon p)Ce. The correlation found between b and [PO4] is due to effects linking nutrient levels to growth rates and cellular carbon budgets for alkenone-containing algae, most likely by trace-metal limitations on algal growth. The relationship reported here is characteristic of 39 samples (r2 = 0.95) from the Santa Monica Basin (six different times during the annual cycle), the equatorial Pacific (boreal spring and fall cruises as well as during an iron-enrichment experiment), and the Peru upwelling zone. Points representative of samples from the Sargasso Sea ([PO4] < or = 0.1 microM) fall above the b = f[PO4] line. Analysis of correlations expected between mu (growth rate), epsilon p, and Ce shows that, for our entire data set, most variations in epsilon p result from variations in mu rather than Ce. Accordingly, before concentrations of dissolved CO2 can be estimated from isotopic fractionations, some means of accounting for variations in growth rate must be found, perhaps by drawing on relationships between [PO4] and Cd/Ca ratios in shells of planktonic foraminifera. PMID:11540616

  10. Consistent fractionation of 13C in nature and in the laboratory: Growth-rate effects in some haptophyte algae

    NASA Astrophysics Data System (ADS)

    Bidigare, Robert R.; Fluegge, Arnim; Freeman, Katherine H.; Hanson, Kristi L.; Hayes, John M.; Hollander, David; Jasper, John P.; King, Linda L.; Laws, Edward A.; Milder, Jeffrey; Millero, Frank J.; Pancost, Richard; Popp, Brian N.; Steinberg, Paul A.; Wakeham, Stuart G.

    1997-06-01

    The carbon isotopic fractionation accompanying formation of biomass by alkenone-producing algae in natural marine environments varies systematically with the concentration of dissolved phosphate. Specifically, if the fractionation is expressed by єP ≈ δe - δp, where δe and δp are the δ13C values for dissolved CO2 and for algal biomass (determined by isotopic analysis of C37 alkadienones), respectively, and if Ce is the concentration of dissolved CO2, μmol kg-1, then b = 38 + 160*[PO4], where [PO4] is the concentration of dissolved phosphate, μM, and b = (25 - єp)Ce. The correlation found between b and [PO4] is due to effects linking nutrient levels to growth rates and cellular carbon budgets for alkenone-containing algae, most likely by trace-metal limitations on algal growth. The relationship reported here is characteristic of 39 samples (r2 = 0.95) from the Santa Monica Basin (six different times during the annual cycle), the equatorial Pacific (boreal spring and fall cruises as well as during an iron-enrichment experiment), and the Peru upwelling zone. Points representative of samples from the Sargasso Sea ([PO4] ≤ 0.1 μM) fall above the b = f[PO4] line. Analysis of correlations expected between μ (growth rate), єp, and Ce shows that, for our entire data set, most variations in єp result from variations in μ rather than Ce. Accordingly, before concentrations of dissolved CO2 can be estimated from isotopic fractionations, some means of accounting for variations in growth rate must be found, perhaps by drawing on relationships between [PO4] and Cd/Ca ratios in shells of planktonic foraminifera.

  11. Optimum dredging time for inhibition and prevention of algae-induced black blooms in Lake Taihu, China.

    PubMed

    Chen, Chao; Zhong, Ji-Cheng; Yu, Ju-Hua; Shen, Qiu-Shi; Fan, Cheng-Xin; Kong, Fan-Xiang

    2016-07-01

    Dredging, which is the removal of polluted surface sediments from a water body, is an effective means of preventing the formation of algae-induced black blooms. However, an inappropriate dredging time may contribute to rather than inhibit the formation of black blooms. To determine the optimum dredging time, four treatments were simulated with sediment samples collected from Lake Taihu: dredging in January 2014 (DW), April 2014 (DA), July 2014 (DS), and no dredging (UD). Results showed that typical characteristics associated with black blooms, such as high levels of nutrients (NH4 (+)-N and PO4 (3-)-P), Fe(2+), ∑S(2-) ([HS(-)] + [S(2-)]), and volatile organic sulfur compounds (VOSCs), including dimethyl sulfide (DMS), dimethyl disulfide (DMDS), and dimethyl trisulfide (DMTS), were more effectively suppressed in the water column by DW treatment than by UD treatment and the other two dredging treatments. The highest concentrations of NH4 (+)-N and PO4 (3-)-P in the UD water column were 4.09 and 4.03 times, respectively, those in the DW water column. DMS levels in the UD and DS water columns were significantly higher (p < 0.05) than those in the DW water column, but DMDS and DMTS levels were not significantly different between the treatments. After several months of dredging, surface sediments of the DW and DA treatments were well oxidized, and concentrations of Fe(2+) and ∑S(2-) were lower than those in UD and DS treatments because of material circulation between sediments and the water column. Water content, which is important for the transport of matter to the overlying water, was lower in the dredged sediments than in the undredged sediments. These factors can suppress the release of Fe(2+) and ∑S(2-) into the water column, thereby inhibiting the formation of black blooms. Black coloration occurred in the UD water column on the seventh day, 2 days later, and earlier, respectively, than the DW and DS water columns and almost on the same day as in the

  12. Spectroscopic analysis of urinary calculi and inhibition of their growth

    NASA Astrophysics Data System (ADS)

    Manciu, Felicia; Durrer, William; Govani, Jayesh; Reza, Layra; Pinales, Luis

    2009-10-01

    We present here a study of kidney stone formation and growth inhibition based on a traditional medicine approach with Aquatica Lour (RAL) herbal extracts. Kidney stone material systems were synthesized in vitro using a simplified single diffusion gel growth technique. With the objective of revealing the mechanism of inhibition of calculi formation by RAL extracts, samples prepared without the presence of extract, and with the presence of extract, were analyzed using Raman, photoluminescence, and XPS. The unexpected presence of Zn revealed by XPS in a sample prepared with RAL provides an explanation for the inhibition process, and also explains the dramatic reflectance of incident light observed in attempts to obtain infrared transmission data. Raman data are consistent with the binding of the inhibitor to the oxygen of the kidney stone. Photoluminescence data corroborate with the other results to provide additional evidence of Zn-related inhibition.

  13. Thymoquinone Inhibits Escherichia coli ATP Synthase and Cell Growth

    PubMed Central

    Ahmad, Zulfiqar; Laughlin, Thomas F.; Kady, Ismail O.

    2015-01-01

    We examined the thymoquinone induced inhibition of purified F1 or membrane bound F1FO E. coli ATP synthase. Both purified F1 and membrane bound F1FO were completely inhibited by thymoquinone with no residual ATPase activity. The process of inhibition was fully reversible and identical in both membrane bound F1Fo and purified F1 preparations. Moreover, thymoquinone induced inhibition of ATP synthase expressing wild-type E. coli cell growth and non-inhibition of ATPase gene deleted null control cells demonstrates that ATP synthase is a molecular target for thymoquinone. This also links the beneficial dietary based antimicrobial and anticancer effects of thymoquinone to its inhibitory action on ATP synthase. PMID:25996607

  14. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    SciTech Connect

    Chang, Cheng-Yi; Kuan, Yu-Hsiang; Ou, Yen-Chuan; Li, Jian-Ri; Wu, Chih-Cheng; Pan, Pin-Ho; Chen, Wen-Ying; Huang, Hsuan-Yi; Chen, Chun-Jung

    2014-09-10

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

  15. Inhibition of estrogen biosynthesis enhances lymphoma growth in mice

    PubMed Central

    Talaber, Gergely; Yakimchuk, Konstantin; Guan, Jiyu; Inzunza, Jose; Okret, Sam

    2016-01-01

    Most lymphomas show higher incidence and poorer prognosis in males compared to females. However, the endocrine contribution to this gender difference is not entirely known. Here we show that castration accelerates lymphoma growth in C57BL6 male mice grafted with murine EG7 T cell lymphoma cells. However, the androgen receptor antagonist Bicalutamide did not affect lymphoma growth, suggesting no impact of androgen receptor signaling on lymphoma progression. In contrast, inhibition of androgen-to-estrogen conversion by the aromatase inhibitor (AI) Letrozole induced faster lymphoma growth in mice, suggesting that androgens impact lymphoma growth through its conversion to estrogens. This was supported by the inability of dihydrotestosterone, which is not converted to estrogens by aromatase, to influence lymphoma growth in castrated male mice. Lymphoma growth was also stimulated in immunocompromised mice grafted with human B cell lymphoma (Granta-519) and treated with either reversible or irreversible AIs, showing that the blockage of estrogen synthesis caused enhanced growth of both murine T and human B cell lymphomas and with different AIs. Additionally, AI-treated EG7 lymphomas showed accelerated growth not only in male but also in intact female mice. Altogether, our results demonstrate that aromatase inhibition accelerates lymphoma growth but not androgens per se, highlighting a protective role of estrogens in lymphoma pathogenesis. These results also raise concern that the use of AIs in women with breast cancer might enhance lymphoma progression. PMID:26943574

  16. The interactive effects of microcystin-LR and cylindrospermopsin on the growth rate of the freshwater algae Chlorella vulgaris.

    PubMed

    Pinheiro, Carlos; Azevedo, Joana; Campos, Alexandre; Vasconcelos, Vítor; Loureiro, Susana

    2016-05-01

    Microcystin-LR (MC-LR) and cylindrospermopsin (CYN) are the most representative cyanobacterial cyanotoxins. They have been simultaneously detected in aquatic systems, but their combined ecotoxicological effects to aquatic organisms, especially microalgae, is unknown. In this study, we examined the effects of these cyanotoxins individually and as a binary mixture on the growth rate of the freshwater algae Chlorella vulgaris. Using the MIXTOX tool, the reference model concentration addition (CA) was selected to evaluate the combined effects of MC-LR and CYN on the growth of the freshwater green algae due to its conservative prediction of mixture effect for putative similar or dissimilar acting chemicals. Deviations from the CA model such as synergism/antagonism, dose-ratio and dose-level dependency were also assessed. In single exposures, our results demonstrated that MC-LR and CYN had different impacts on the growth rates of C. vulgaris at the highest tested concentrations, being CYN the most toxic. In the mixture exposure trial, MC-LR and CYN showed a synergistic deviation from the conceptual model CA as the best descriptive model. MC-LR individually was not toxic even at high concentrations (37 mg L(-1)); however, the presence of MC-LR at much lower concentrations (0.4-16.7 mg L(-1)) increased the CYN toxicity. From these results, the combined exposure of MC-LR and CYN should be considered for risk assessment of mixtures as the toxicity may be underestimated when looking only at the single cyanotoxins and not their combination. This study also represents an important step to understand the interactions among MC-LR and CYN detected previously in aquatic systems. PMID:26910533

  17. Host specificity and growth of kelp gametophytes symbiotic with filamentous red algae (Ceramiales, Rhodophyta)

    NASA Astrophysics Data System (ADS)

    Hubbard, Charlene B.; Garbary, David J.; Kim, Kwang Young; Chiasson, David M.

    2004-02-01

    Kelp gametophytes were previously observed in nature living endophytically in red algal cell walls. Here we examine the interactions of two kelp species and six red algae in culture. Gametophytes of Nereocystis luetkeana (Mertens) Postels et Ruprecht became endophytic in the cell walls of Griffithsia pacifica Kylin and Antithamnion defectum Kylin, and grew epiphytically in high abundance on G. japonica Okamura and Aglaothamnion oosumiense Itono. Alaria esculenta (Linnaeus) Greville from the Atlantic coast of Nova Scotia became endophytic in Aglaothamnion oosumiense, Antithamnion defectum, Callithamnion sp., G. japonica, G. pacifica, and Pleonosporium abysicola Gardner, all from the Pacific Ocean. Some cultures were treated with phloroglucinol before infection to thicken the cell walls. The endophytic gametophytes were smaller and grew more slowly than gametophytes epiphytic on the same host. N. luetkeana failed to become endophytic in some of the potential hosts, and this may reflect host specificity, or culture artifacts. This work improves our understanding of the process of infection of red algae by kelp gametophytes, and broadens our knowledge of host specificity in endophytic symbioses.

  18. Toxic effects of organic solvents on the growth of blue-green algae

    SciTech Connect

    Stratton, G.W.

    1987-06-01

    Relatively few reports have been published on the comparative toxicity of solvents towards test organisms, and these deal primarily with fish and aquatic invertebrates. Information for microbial systems are more limited with some data available for algae and slightly more for fungi. Aside from direct toxic effects of their own, solvents can interact synergistically and antagonistically with the toxicant in solution. This problem has been well documented with pesticides, and a procedure has been developed to identify and eliminate these effects from bioassays. The first step in choosing a solvent for use in microbial bioassays should be a detailed screening to identify solvents with inherently low toxicity to the test organism, followed by an interaction study to choose the best concentration to use. The purpose of the present study was to compare the inhibitory effects of six solvents commonly used in pesticide bioassays towards five species of blue-green algae (cyanobacteria), in order to identify solvents with low toxicity for use in bioassays.

  19. Anti-Phytopathogenic Activities of Macro-Algae Extracts

    PubMed Central

    Jiménez, Edra; Dorta, Fernando; Medina, Cristian; Ramírez, Alberto; Ramírez, Ingrid; Peña-Cortés, Hugo

    2011-01-01

    Aqueous and ethanolic extracts obtained from nine Chilean marine macro-algae collected at different seasons were examined in vitro and in vivo for properties that reduce the growth of plant pathogens or decrease the injury severity of plant foliar tissues following pathogen infection. Particular crude aqueous or organic extracts showed effects on the growth of pathogenic bacteria whereas others displayed important effects against pathogenic fungi or viruses, either by inhibiting fungal mycelia growth or by reducing the disease symptoms in leaves caused by pathogen challenge. Organic extracts obtained from the brown-alga Lessonia trabeculata inhibited bacterial growth and reduced both the number and size of the necrotic lesion in tomato leaves following infection with Botrytis cinerea. Aqueous and ethanolic extracts from the red-alga Gracillaria chilensis prevent the growth of Phytophthora cinnamomi, showing a response which depends on doses and collecting-time. Similarly, aqueous and ethanolic extracts from the brown-alga Durvillaea antarctica were able to diminish the damage caused by tobacco mosaic virus (TMV) in tobacco leaves, and the aqueous procedure is, in addition, more effective and seasonally independent. These results suggest that macro-algae contain compounds with different chemical properties which could be considered for controlling specific plant pathogens. PMID:21673886

  20. Anti-phytopathogenic activities of macro-algae extracts.

    PubMed

    Jiménez, Edra; Dorta, Fernando; Medina, Cristian; Ramírez, Alberto; Ramírez, Ingrid; Peña-Cortés, Hugo

    2011-01-01

    Aqueous and ethanolic extracts obtained from nine Chilean marine macro-algae collected at different seasons were examined in vitro and in vivo for properties that reduce the growth of plant pathogens or decrease the injury severity of plant foliar tissues following pathogen infection. Particular crude aqueous or organic extracts showed effects on the growth of pathogenic bacteria whereas others displayed important effects against pathogenic fungi or viruses, either by inhibiting fungal mycelia growth or by reducing the disease symptoms in leaves caused by pathogen challenge. Organic extracts obtained from the brown-alga Lessonia trabeculata inhibited bacterial growth and reduced both the number and size of the necrotic lesion in tomato leaves following infection with Botrytis cinerea. Aqueous and ethanolic extracts from the red-alga Gracillaria chilensis prevent the growth of Phytophthora cinnamomi, showing a response which depends on doses and collecting-time. Similarly, aqueous and ethanolic extracts from the brown-alga Durvillaea antarctica were able to diminish the damage caused by tobacco mosaic virus (TMV) in tobacco leaves, and the aqueous procedure is, in addition, more effective and seasonally independent. These results suggest that macro-algae contain compounds with different chemical properties which could be considered for controlling specific plant pathogens. PMID:21673886

  1. [Inhibition of growth of microscopic fungi with organic acids].

    PubMed

    Conková, E; Para, L; Kocisová, A

    1993-01-01

    Fungicidal effects of five selected organic acids (lactic, acetic, formic, oxalic, and propionic) in concentrations 3, 5, 10, 20 and 50 ml/l on nine selected species of moulds were tested. Lactic and oxalic acids did not prove the satisfactory fungicidal activity in any of the chosen concentrations. The antifungal effect of the other three acids, manifested by the growth inhibition of the tested moulds is shown in Tab. I and it can be expressed by sequence: propionic acid, formic acid, and acetic acid. These acids also had effects only in concentrations 20 ml/l and 50 ml/l. Propionic acid in concentration 20 ml/l inhibited the growth of five moulds (Penicillium glabrum, Aspergillus niger, Fusarium moniliforme, Aspergillus fumigatus, Cladosporium sphaerospermum). In testing of concentration 50 ml/l, the lower fungicidal ability was ascertained only in growth suppression of Aspergillus flavus. The fungicidal activity of formic acid was registered in concentration 20 ml/l in two cases and in concentration 50 ml/l in six cases. Acetic acid inhibited the growth in concentration 50 ml/l only in two cases. Tab. II shows the percentual evaluation of propionic acid and formic acid with regard to their inhibition abilities. The fungicidal efficiency of propionic acid resulting from the experiment is 88.9%. PMID:8122343

  2. A lipid-accumulating alga maintains growth in outdoor, alkaliphilic raceway pond with mixed microbial communities

    DOE PAGESBeta

    Bell, Tisza A.S.; Prithiviraj, Bharath; Wahlen, Brad D.; Fields, Matthew W.; Peyton, Brent M.

    2016-01-07

    Algal biofuels and valuable co-products are being produced in both open and closed cultivation systems. Growing algae in open pond systems may be a more economical alternative, but this approach allows environmental microorganisms to colonize the pond and potentially infect or outcompete the algal “crop.” In this study, we monitored the microbial community of an outdoor, open raceway pond inoculated with a high lipid-producing alkaliphilic alga, Chlorella vulgaris BA050. The strain C. vulgaris BA050 was previously isolated from Soap Lake, Washington, a system characterized by a high pH (~9.8). An outdoor raceway pond (200 L) was inoculated with C. vulgarismore » and monitored for 10 days and then the culture was transferred to a 2,000 L raceway pond and cultivated for an additional 6 days. Community DNA samples were collected over the 16-day period in conjunction with water chemistry analyses and cell counts. Universal primers for the SSU rRNA gene sequences for Eukarya, Bacteria, and Archaea were used for barcoded pyrosequence determination. The environmental parameters that most closely correlated with C. vulgaris abundance were pH and phosphate. Community analyses indicated that the pond system remained dominated by the Chlorella population (93% of eukaryotic sequences), but was also colonized by other microorganisms. Bacterial sequence diversity increased over time while archaeal sequence diversity declined over the same time period. Using SparCC co-occurrence network analysis, a positive correlation was observed between C. vulgaris and Pseudomonas sp. throughout the experiment, which may suggest a symbiotic relationship between the two organisms. The putative relationship coupled with high pH may have contributed to the success of C. vulgaris. As a result, the characterization of the microbial community dynamics of an alkaliphilic open pond system provides significant insight into open pond systems that could be used to control photoautotrophic biomass

  3. A Lipid-Accumulating Alga Maintains Growth in Outdoor, Alkaliphilic Raceway Pond with Mixed Microbial Communities

    PubMed Central

    Bell, Tisza A. S.; Prithiviraj, Bharath; Wahlen, Brad D.; Fields, Matthew W.; Peyton, Brent M.

    2016-01-01

    Algal biofuels and valuable co-products are being produced in both open and closed cultivation systems. Growing algae in open pond systems may be a more economical alternative, but this approach allows environmental microorganisms to colonize the pond and potentially infect or outcompete the algal “crop.” In this study, we monitored the microbial community of an outdoor, open raceway pond inoculated with a high lipid-producing alkaliphilic alga, Chlorella vulgaris BA050. The strain C. vulgaris BA050 was previously isolated from Soap Lake, Washington, a system characterized by a high pH (∼9.8). An outdoor raceway pond (200 L) was inoculated with C. vulgaris and monitored for 10 days and then the culture was transferred to a 2,000 L raceway pond and cultivated for an additional 6 days. Community DNA samples were collected over the 16-day period in conjunction with water chemistry analyses and cell counts. Universal primers for the SSU rRNA gene sequences for Eukarya, Bacteria, and Archaea were used for barcoded pyrosequence determination. The environmental parameters that most closely correlated with C. vulgaris abundance were pH and phosphate. Community analyses indicated that the pond system remained dominated by the Chlorella population (93% of eukaryotic sequences), but was also colonized by other microorganisms. Bacterial sequence diversity increased over time while archaeal sequence diversity declined over the same time period. Using SparCC co-occurrence network analysis, a positive correlation was observed between C. vulgaris and Pseudomonas sp. throughout the experiment, which may suggest a symbiotic relationship between the two organisms. The putative relationship coupled with high pH may have contributed to the success of C. vulgaris. The characterization of the microbial community dynamics of an alkaliphilic open pond system provides significant insight into open pond systems that could be used to control photoautotrophic biomass productivity in an

  4. A Lipid-Accumulating Alga Maintains Growth in Outdoor, Alkaliphilic Raceway Pond with Mixed Microbial Communities.

    PubMed

    Bell, Tisza A S; Prithiviraj, Bharath; Wahlen, Brad D; Fields, Matthew W; Peyton, Brent M

    2015-01-01

    Algal biofuels and valuable co-products are being produced in both open and closed cultivation systems. Growing algae in open pond systems may be a more economical alternative, but this approach allows environmental microorganisms to colonize the pond and potentially infect or outcompete the algal "crop." In this study, we monitored the microbial community of an outdoor, open raceway pond inoculated with a high lipid-producing alkaliphilic alga, Chlorella vulgaris BA050. The strain C. vulgaris BA050 was previously isolated from Soap Lake, Washington, a system characterized by a high pH (∼9.8). An outdoor raceway pond (200 L) was inoculated with C. vulgaris and monitored for 10 days and then the culture was transferred to a 2,000 L raceway pond and cultivated for an additional 6 days. Community DNA samples were collected over the 16-day period in conjunction with water chemistry analyses and cell counts. Universal primers for the SSU rRNA gene sequences for Eukarya, Bacteria, and Archaea were used for barcoded pyrosequence determination. The environmental parameters that most closely correlated with C. vulgaris abundance were pH and phosphate. Community analyses indicated that the pond system remained dominated by the Chlorella population (93% of eukaryotic sequences), but was also colonized by other microorganisms. Bacterial sequence diversity increased over time while archaeal sequence diversity declined over the same time period. Using SparCC co-occurrence network analysis, a positive correlation was observed between C. vulgaris and Pseudomonas sp. throughout the experiment, which may suggest a symbiotic relationship between the two organisms. The putative relationship coupled with high pH may have contributed to the success of C. vulgaris. The characterization of the microbial community dynamics of an alkaliphilic open pond system provides significant insight into open pond systems that could be used to control photoautotrophic biomass productivity in an open

  5. Algae Derived Biofuel

    SciTech Connect

    Jahan, Kauser

    2015-03-31

    One of the most promising fuel alternatives is algae biodiesel. Algae reproduce quickly, produce oils more efficiently than crop plants, and require relatively few nutrients for growth. These nutrients can potentially be derived from inexpensive waste sources such as flue gas and wastewater, providing a mutual benefit of helping to mitigate carbon dioxide waste. Algae can also be grown on land unsuitable for agricultural purposes, eliminating competition with food sources. This project focused on cultivating select algae species under various environmental conditions to optimize oil yield. Membrane studies were also conducted to transfer carbon di-oxide more efficiently. An LCA study was also conducted to investigate the energy intensive steps in algae cultivation.

  6. Effects of Dried Algae Schizochytrium Sp., A Rich Source of Docosahexaenoic Acid, on Growth, Fatty Acid Composition, and Sensory Quality of Channel Catfish Ictalurus Punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A laboratory study was conducted to investigate the effect of supplementation of dried algae Schizochytrium sp., a rich source of 22:6 n-3, on growth, fatty acid composition, and sensory quality of channel catfish Ictalurus punctatus. Five isonitrogenous (28% crude protein) and isocaloric (2.78 kcal...

  7. Saccharin and Cyclamate Inhibit Binding of Epidermal Growth Factor

    NASA Astrophysics Data System (ADS)

    Lee, L. S.

    1981-02-01

    The binding of 125I-labeled mouse epidermal growth factor (EGF) to 18 cell lines, including HeLa (human carcinoma), MDCK (dog kidney cells), HTC (rat hepatoma), K22 (rat liver), HF (human foreskin), GM17 (human skin fibroblasts), XP (human xeroderma pigmentosum fibroblasts), and 3T3-L1 (mouse fibroblasts), was inhibited by saccharin and cyclamate. The human cells were more sensitive to inhibition by these sweeteners than mouse or rat cells. EGF at doses far above the physiological levels reversed the inhibition in rodent cells but not in HeLa cells. In HeLa cells, the doses of saccharin and cyclamate needed for 50% inhibition were 3.5 and 9.3 mg/ml, respectively. Glucose, 2-deoxyglucose, sucrose, and xylitol did not inhibit EGF binding. Previous studies have shown that phorbol esters, strongly potent tumor promoters, also inhibit EGF binding to tissue culture cells. To explain the EGF binding inhibition by such greatly dissimilar molecules as phorbol esters, saccharin, and cyclamate, it is suggested that they operate through the activation of a hormone response control unit.

  8. Decreased growth-induced water potential: A primary cause of growth inhibition at low water potentials

    SciTech Connect

    Nonami, Hiroshi; Wu, Yajun; Boyer, J.S.

    1997-06-01

    Cell enlargement depends on a growth-induced difference in water potential to move water into the cells. Water deficits decrease this potential difference and inhibit growth. To investigate whether the decrease causes the growth inhibition, pressure was applied to the roots of soybean seedlings and the growth and potential difference were monitored in the stems. In water-limited plants, the inhibited stem growth increased when the roots were pressurized and it reverted to the previous rate when the pressure was released. The pressure around the roots was perceived as an increased turgor in the stem in small cells next to the xylem, but not in outlying cortical cells. This local effect implied that water transport was impeded by the small cells. The diffusivity for water was much less in the small cells than in the outlying cells. The small cells thus were a barrier that caused the growth-induced potential difference to be large during rapid growth, but to reverse locally during the early part of a water deficit. Such a barrier may be a frequent property of meristems. Because stem growth responded to the pressure-induced recovery of the potential difference across this barrier, we conclude that a decrease in the growth-induced potential difference was a primary cause of the inhibition.

  9. Growth-inhibitory effects of a mineralized extract from the red marine algae, Lithothamnion calcareum, on Ca2+-sensitive and Ca2+-resistant human colon carcinoma cells

    PubMed Central

    Nadeem Aslam, Muhammad; Bhagavathula, Narasimharao; Paruchuri, Tejaswi; Hu, Xin; Chakrabarty, Subhas; Varani, James

    2009-01-01

    Proliferation and differentiation were assessed in a series of human colon carcinoma cell lines in response to a mineral-rich extract derived from the red marine algae, Lithothamnion calcareum. The extract contains 12% Ca2+, 1% Mg2+, and detectable amounts of 72 trace elements, but essentially no organic material. The red algae extract was as effective as inorganic Ca2+ alone in suppressing growth and inducing differentiation of colon carcinoma cells that are responsive to a physiological level of extracellular Ca2+ (1.4 mM). However, with cells that are resistant to Ca2+ alone, the extract was still able to reduce proliferation and stimulate differentiation. PMID:19394137

  10. Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.

    PubMed

    Vediyappan, Govindsamy; Dumontet, Vincent; Pelissier, Franck; d'Enfert, Christophe

    2013-01-01

    Candida albicans is an opportunistic and polymorphic fungal pathogen that causes mucosal, disseminated and invasive infections in humans. Transition from the yeast form to the hyphal form is one of the key virulence factors in C. albicans contributing to macrophage evasion, tissue invasion and biofilm formation. Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and hyphal growth could represent a valuable source for understanding pathogenic fungal morphogenesis, identifying drug targets and serving as templates for the development of novel antifungal agents. Here, we have identified the triterpenoid saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis. GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic traditional medicinal plant used to treat diabetes. Purified GAs had no effect on the growth and viability of C. albicans yeast cells but inhibited its yeast-to-hypha conversion under several hypha-inducing conditions, including the presence of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast cells under hypha inducing conditions. They also inhibited conidial germination and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and rescued them from killing by C. albicans. Hence, GAs could be useful for various antifungal applications due to their traditional use in herbal medicine. PMID:24040201

  11. In vitro inhibition of struvite crystal growth by acetohydroxamic acid.

    PubMed

    Downey, J A; Nickel, J C; Clapham, L; McLean, R J

    1992-10-01

    Struvite (MgNH4PO46H2O) crystals were produced by Proteus mirabilis growth in artificial urine, in the presence and absence of the urease inhibitor, acetohydroxamic acid (AHA). In the absence of AHA, struvite crystals assumed an "X-shaped" or dendritic crystal habit due to rapid growth along their 100 axis. When AHA was present, crystal growth, as monitored by phase contrast light microscopy, was greatly slowed, and the crystals assumed an octahedral crystal habit. Scanning electron microscopy revealed that crystals grown in the presence of AHA were pitted on their surface. This pitting was absent in control samples. While most of this inhibition by AHA was due to lowered urease activity, some crystal growth inhibition occurred in struvite produced in the absence of urease activity through NH4OH titration of artificial urine. We conclude that while AHA is primarily a urease inhibitor, it may also disrupt struvite growth and formation directly through interference with the molecular growth processes on crystal surfaces. PMID:1450840

  12. Apicoplast-Targeting Antibacterials Inhibit the Growth of Babesia Parasites

    PubMed Central

    AbouLaila, Mahmoud; Munkhjargal, Tserendorj; Sivakumar, Thillaiampalam; Ueno, Akio; Nakano, Yuki; Yokoyama, Miki; Yoshinari, Takeshi; Nagano, Daisuke; Katayama, Koji; El-Bahy, Nasr; Yokoyama, Naoaki

    2012-01-01

    The apicoplast housekeeping machinery, specifically apicoplast DNA replication, transcription, and translation, was targeted by ciprofloxacin, thiostrepton, and rifampin, respectively, in the in vitro cultures of four Babesia species. Furthermore, the in vivo effect of thiostrepton on the growth cycle of Babesia microti in BALB/c mice was evaluated. The drugs caused significant inhibition of growth from an initial parasitemia of 1% for Babesia bovis, with 50% inhibitory concentrations (IC50s) of 8.3, 11.5, 12, and 126.6 μM for ciprofloxacin, thiostrepton, rifampin, and clindamycin, respectively. The IC50s for the inhibition of Babesia bigemina growth were 15.8 μM for ciprofloxacin, 8.2 μM for thiostrepton, 8.3 μM for rifampin, and 206 μM for clindamycin. The IC50s for Babesia caballi were 2.7 μM for ciprofloxacin, 2.7 μM for thiostrepton, 4.7 μM for rifampin, and 4.7 μM for clindamycin. The IC50s for the inhibition of Babesia equi growth were 2.5 μM for ciprofloxacin, 6.4 μM for thiostrepton, 4.1 μM for rifampin, and 27.2 μM for clindamycin. Furthermore, an inhibitory effect was revealed for cultures with an initial parasitemia of either 10 or 7% for Babesia bovis or Babesia bigemina, respectively. The three inhibitors caused immediate death of Babesia bovis and Babesia equi. The inhibitory effects of ciprofloxacin, thiostrepton, and rifampin were confirmed by reverse transcription-PCR. Thiostrepton at a dose of 500 mg/kg of body weight resulted in 77.5% inhibition of Babesia microti growth in BALB/c mice. These results implicate the apicoplast as a potential chemotherapeutic target for babesiosis. PMID:22391527

  13. [Toxicity of Coptis chinensis Rhizome Extracts to Green Algae].

    PubMed

    Chen, Ya-nan; Yuan, Ling

    2015-05-01

    Coptis chinensis contains antiseptic alkaloids and thus its rhizomes and preparations are widely used for the treatment of.fish diseases. In order to realize the risk of water ecosystems produced by this medical herb and preparations used in aquaculture, the present experiment was carried out to study the toxicity of Coptis chinensis rhizome extract (CRE) to Scenedesmus oblique and Chlorella pyrenoidosa grown in culture solution with 0.00 (CK), 0.088 (Tl), 0.44 (T2) and 1.76 mg · L(-1) (T3) of CRE, respectively. The results show that low concentration of CRE (T1) inhibited the growth rate of the alga and high CRE (T2 and T3) ceased growth and reproductions. CRE also decreased the chlorophyll and proteins in alga cells, indicating the inhibition of photosynthesis and protein biosynthesis, which could be direct reasons for the low growth rate and death of green alga. The efflux of protons and substances from alga cells led to pH reduction and conductivity increment in culture solution with CRE. Furthermore, the activity of superoxide dismutase in alga increased at the beginning of CRE in T1 and T2 treatments but decreased as time prolonged which was in contrast to high CRE treatment. And the long exposure to low CRE treatment behaved otherwise. This suggests that the low concentration of CRE could induce the resistant reactions in alga at initial time but high CRE concentration or long exposure even at low CRE concentration could inhibit the enzyme synthesis. Similarly, malondialdehyde in alga increased as CRE concentrations increased in culture solutions, implying the damage and high permeability of cell membrane. In general, Chlorella pyrenoidosa was more sensitive to CRE. The abuse of rhizomes and preparations in aquaculture and intensive cultivation of Coptis chinensis plants in a large scale might produce ecological risks to primary productivity of water ecosystems. PMID:26314112

  14. Biological toxicity of lanthanide elements on algae.

    PubMed

    Tai, Peidong; Zhao, Qing; Su, Dan; Li, Peijun; Stagnitti, Frank

    2010-08-01

    The biological toxicity of lanthanides on marine monocellular algae was investigated. The specific objective of this research was to establish the relationship between the abundance in the seawater of lanthanides and their biological toxicities on marine monocellular algae. The results showed that all single lanthanides had similar toxic effects on Skeletonema costatum. High concentrations of lanthanides (29.04+/-0.61 micromol L(-1)) resulted in 50% reduction in growth of algae compared to the controls (0 micromol L(-1)) after 96 h (96 h-EC50). The biological toxicity of 13 lanthanides on marine monocellular algae was unrelated with the abundance of different lanthanide elements in nature, and the "Harkins rule" was not appropriate for the lanthanides. A mixed solution that contained equivalent concentrations of each lanthanide element had the same inhibition effect on algae cells as each individual lanthanide element at the same total concentration. This phenomenon is unique compared to the groups of other elements in the periodic table. Hence, we speculate that the monocellular organisms might not be able to sufficiently differentiate between the almost chemically identical lanthanide elements. PMID:20547408

  15. Effect of Ocean acidification on growth, calcification and recruitment of calcifying and non-calcifying epibionts of brown algae

    NASA Astrophysics Data System (ADS)

    Saderne, V.; Wahl, M.

    2012-03-01

    Anthropogenic emissions of CO2 are leading to an acidification of the oceans by 0.4 pH units in the course of this century according to the more severe model scenarios. The excess of CO2 could notably affect the benthic communities of calcifiers and macrophytes in different aspects (photosynthesis, respiration and calcification). Seaweeds are key species of nearshore benthic ecosystems of the Baltic Sea. They frequently are the substratum of fouling epibionts like bryozoans and tubeworms. Most of those species secrete calcified structures and could therefore be impacted by the seawater pCO2. On the other hand, the biological activity of the host may substantially modulate the pH and pCO2 conditions in the thallus boundary layer where the epibionts live. The aim of the present study was to test the sensitivity of seaweed macrofouling communities to higher pCO2 concentrations. Fragments of the macroalga Fucus serratus bearing the calcifiers Spirorbis spirorbis (Annelida) and Electra pilosa (Bryozoa) and the non-calcifier Alcyonidium gelatinosum (Bryozoa) were maintained for 30 days under three pCO2 conditions: natural 460 ± 59 μatm and enriched 1193 ± 166 μatm and 3150 ± 446 μatm. Our study showed a significant reduction of growth rates and recruitment of Spirorbis individuals only at the highest pCO2. At a finer temporal resolution, the tubeworm recruits exhibited enhanced calcification of 40% during irradiation hours compared to dark hours, presumably due to the effect of photosynthetic and respiratory activities of the host alga on the carbonate system. Electra colonies showed significantly increased growth rates at 1193 μatm. No effect on Alcyonidium colonies growth rates was observed. Those results suggest a remarkable resistance of the algal macro-epibiontic communities to the most elevated pCO2 foreseen in year 2100 for open ocean (~1000 μatm) conditions possibly due to the modulation of environmental conditions by the biological activities of the host

  16. Selective potentiation of lometrexol growth inhibition by dipyridamole through cell-specific inhibition of hypoxanthine salvage.

    PubMed Central

    Turner, R. N.; Aherne, G. W.; Curtin, N. J.

    1997-01-01

    The novel antifolate lometrexol (5,10-dideazatetrahydrofolate) inhibits de novo purine biosynthesis, and co-incubation with hypoxanthine abolishes its cytotoxicity. The prevention of hypoxanthine rescue from an antipurine antifolate by the nucleoside transport inhibitor dipyridamole was investigated for the first time in nine human and rodent cell lines from seven different tissues of origin. In A549, HeLa and CHO cells, dipyridamole prevented hypoxanthine rescue and so growth was inhibited by the combination of lometrexol, dipyridamole and hypoxanthine, but in HT29, HCT116, KK47, MDA231, CCRF CEM and L1210 cells dipyridamole had no effect and the combination did not inhibit growth. Dipyridamole inhibited hypoxanthine uptake in A549 but not in CCRF CEM cells. Dipyridamole prevented the hypoxanthine-induced repletion of dGTP pools, depleted by lometrexol, in A549 but not in CCRF CEM cells. Thus, the selective growth-inhibitory effect of the combination of lometrexol, dipyridamole and hypoxanthine is apparently due to the dipyridamole sensitivity (ds) or insensitivity (di) of hypoxanthine transport. Both the human and murine leukaemic cells are of the di phenotype. If this reflects the transport phenotype of normal bone marrow it would suggest that the combination of lometrexol, dipyridamole and hypoxanthine might be selectively toxic to certain tumour types and have reduced toxicity to the bone marrow. PMID:9374375

  17. Growth of Streptococcus mutans protoplasts is not inhibited by penicillin.

    PubMed Central

    Parks, L C; Shockman, G D; Higgins, M L

    1980-01-01

    A method is described in which cells of Streptococcus mutans BHT can be converted to spherical, osmotically fragile protoplasts. Exponential-phase cells were suspended in a solution containing 0.5 M melezitose, and their cell walls were hydrolyzed with mutanolysin (M-1 enzyme). When the resultant protoplasts were incubated in a chemically defined growth medium containing 0.5 M NH4Cl, the protoplast suspensions increased in turbidity, protein, ribonucleic acid, and deoxyribonucleic acid in a balanced fashion. In the presence of benzylpenicillin (5 microgram/ml), balanced growth of protoplasts was indistinguishable from untreated controls. This absence of inhibition of protoplast growth in the presence of benzylpenicillin was apparently not due to inactivation of the antibiotic. When exponential-phase cells of S. mutans BHT were first exposed to 5 microgram of benzyl-penicillin per ml for 1 h and then converted to protoplasts, these protoplasts were also able to grow in chemically defined, osmotically stabilized medium. The ability of wall-free protoplasts to grow and to synthesize ribonucleic acid and protein in the presence of a relatively high concentration of benzylpenicillin contrasts with the previously reported rapid inhibition of ribonucleic acid and protein synthesis in intact streptococci. These data suggest that this secondary inhibition of ribonucleic acid and protein synthesis in whole cells is due to factors involved with the continued assembly of an intact, insoluble cell wall rather than with earlier stages of peptidoglycan synthesis. Images PMID:6997274

  18. Nur77 inhibits androgen-induced bladder cancer growth.

    PubMed

    Wu, Jianping; Liu, Jun; Jia, Ruipeng; Song, Hongbin

    2013-12-01

    Currently, bladder cancer ranks as the second most common genitourinary malignancy which is exacting significant morbidity and mortality worldwide. Although there are abundant epidemiological and basic studies which strongly suggest the role of androgen hormone in bladder cancer, the underlying mechanism is not fully understood. In the current study, we sought to identify a new competitive inhibitor for androgen receptor in bladder cancer cells. Our results showed that Nur77 hyperexpression inhibits UM-UC-3 cell growth and cell cycle progression while Nur77 knockdown exerts the opposite effect. In our cell culture model, we also demonstrated that Nur77 competitively inhibits androgen-dependent transcription activity and more specifically, Nur77 competes with androgen receptor for binding to src-1, a well-known coactivator for steroids. More importantly, we also showed that a small molecule agonist for Nur77, Cytosporone B, significantly inhibits androgen-dependent bladder cancer cell growth in two different cell lines. These data provide a good proof-of-principle that Nur77 signaling machinery could be a new target for growth control of androgen-dependent bladder cancer cells. PMID:24299210

  19. FH535 inhibited metastasis and growth of pancreatic cancer cells

    PubMed Central

    Wu, Meng-Yao; Liang, Rong-Rui; Chen, Kai; Shen, Meng; Tian, Ya-Li; Li, Dao-Ming; Duan, Wei-Ming; Gui, Qi; Gong, Fei-Ran; Lian, Lian; Li, Wei; Tao, Min

    2015-01-01

    FH535 is a small-molecule inhibitor of the Wnt/β-catenin signaling pathway, which a substantial body of evidence has proven is activated in various cancers, including pancreatic cancer. Activation of the Wnt/β-catenin pathway plays an important role in tumor progression and metastasis. We investigated the inhibitory effect of FH535 on the metastasis and growth of pancreatic cancer cells. Western blotting and luciferase reporter gene assay indicated that FH535 markedly inhibited Wnt/β-catenin pathway viability in pancreatic cancer cells. In vitro wound healing, invasion, and adhesion assays revealed that FH535 significantly inhibited pancreatic cancer cell metastasis. We also observed the inhibitory effect of FH535 on pancreatic cancer cell growth via the tetrazolium and plate clone formation assays. Microarray analyses suggested that changes in the expression of multiple genes could be involved in the anti-cancer effect of FH535 on pancreatic cancer cells. Our results indicate for the first time that FH535 inhibits pancreatic cancer cell metastasis and growth, providing new insight into therapy of pancreatic cancer. PMID:26185454

  20. Nordihydroguaiaretic Acid Inhibits Insulin-Like Growth Factor Signaling, Growth, and Survival in Human Neuroblastoma Cells

    PubMed Central

    Meyer, Gary E.; Chesler, Louis; Liu, Dandan; Gable, Karissa; Maddux, Betty A.; Goldenberg, David D.; Youngren, Jack F.; Goldfine, Ira D.; Weiss, William A.; Matthay, Katherine K.; Rosenthal, Stephen M.

    2010-01-01

    Neuroblastoma is a common pediatric malignancy that metastasizes to the liver, bone, and other organs. Children with metastatic disease have a less than 50% chance of survival with current treatments. Insulin-like growth factors (IGFs) stimulate neuroblastoma growth, survival, and motility, and are expressed by neuroblastoma cells and the tissues they invade. Thus, therapies that disrupt the effects of IGFs on neuroblastoma tumorigenesis may slow disease progression. We show that NVP-AEW541, a specific inhibitor of the IGF-I receptor (IGF-IR), potently inhibits neuroblastoma growth in vitro. Nordihydroguaiaretic acid (NDGA), a phenolic compound isolated from the creosote bush (Larrea divaricata), has anti-tumor properties against a number of malignancies, has been shown to inhibit the phosphorylation and activation of the IGF-IR in breast cancer cells, and is currently in Phase I trials for prostate cancer. In the present study in neuroblastoma, NDGA inhibits IGF-I-mediated activation of the IGF-IR and disrupts activation of ERK and Akt signaling pathways induced by IGF-I. NDGA inhibits growth of neuroblastoma cells and induces apoptosis at higher doses, causing IGF-I-resistant activation of caspase-3 and a large increase in the fraction of sub-G0 cells. In addition, NDGA inhibits the growth of xenografted human neuroblastoma tumors in nude mice. These results indicate that NDGA may be useful in the treatment of neuroblastoma and may function in part via disruption of IGF-IR signaling. PMID:17486636

  1. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro.

    PubMed

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A

    2016-03-15

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. PMID:26876617

  2. Growth inhibition of cultured marine phytoplankton by toxic algal-derived polyunsaturated aldehydes.

    PubMed

    Ribalet, François; Berges, John A; Ianora, Adrianna; Casotti, Raffaella

    2007-12-15

    Several marine diatoms produce polyunsaturated aldehydes (PUAs) that have been shown to be toxic to a wide variety of model organisms, from bacteria to invertebrates. However, very little information is available on their effect on phytoplankton. Here, we expand previous studies to six species of marine phytoplankton, belonging to different taxonomic groups that are well represented in marine plankton. The effect of three PUAs, 2E,4E-decadienal, 2E,4E-octadienal and 2E,4E-heptadienal, was assessed on growth, cell membrane permeability, flow cytometric properties and morphology. A concentration-dependent reduction in the growth rate was observed for all cultures exposed to PUAs with longer-chained aldehydes having stronger effects on growth than shorter-chained aldehydes. Clear differences were observed among the different species. The prymnesiophyte Isochrysis galbana was the most sensitive species to PUA exposure with a lower threshold for an observed effect triggered by mean concentrations of 0.10 micromol L(-1) for 2E,4E-decadienal, 1.86 micromol L(-1) for 2E,4E-octadienal and 3.06 micromol L(-1) for 2E,4E-heptadienal, and a 50% growth inhibition (EC(50)) with respect to the control at 0.99, 2.25 and 5.90 micromol L(-1) for the three PUAs, respectively. Alternatively, the chlorophyte Tetraselmis suecica and the diatom Skeletonema marinoi (formerly S. costatum) were the most resistant species with 50% growth inhibition occurring at concentrations at least two to three times higher than I. galbana. In all species, the three PUAs caused changes in flow cytometric measures of cell size and cell granulosity and increased membrane permeability, assessed using the viability stain SYTOX Green. For example, after 48 h 51.6+/-2.6% of I. galbana cells and 15.0+/-1.8% of S. marinoi cells were not viable. Chromatin fragmentation was observed in the dinoflagellate Amphidinium carterae while clear DNA degradation was observed in the chlorophyte Dunaliella tertiolecta

  3. In-Situ Effects of Simulated Overfishing and Eutrophication on Benthic Coral Reef Algae Growth, Succession, and Composition in the Central Red Sea

    PubMed Central

    Jessen, Christian; Roder, Cornelia; Villa Lizcano, Javier Felipe; Voolstra, Christian R.; Wild, Christian

    2013-01-01

    Overfishing and land-derived eutrophication are major local threats to coral reefs and may affect benthic communities, moving them from coral dominated reefs to algal dominated ones. The Central Red Sea is a highly under-investigated area, where healthy coral reefs are contending against intense coastal development. This in-situ study investigated both the independent and combined effects of manipulated inorganic nutrient enrichment (simulation of eutrophication) and herbivore exclosure (simulation of overfishing) on benthic algae development. Light-exposed and shaded terracotta tiles were positioned at an offshore patch reef close to Thuwal, Saudi Arabia and sampled over a period of 4 months. Findings revealed that nutrient enrichment alone affected neither algal dry mass nor algae-derived C or N production. In contrast, herbivore exclusion significantly increased algal dry mass up to 300-fold, and in conjunction with nutrient enrichment, this total increased to 500-fold. Though the increase in dry mass led to a 7 and 8-fold increase in organic C and N content, respectively, the algal C/N ratio (18±1) was significantly lowered in the combined treatment relative to controls (26±2). Furthermore, exclusion of herbivores significantly increased the relative abundance of filamentous algae on the light-exposed tiles and reduced crustose coralline algae and non-coralline red crusts on the shaded tiles. The combination of the herbivore exclusion and nutrient enrichment treatments pronounced these effects. The results of our study suggest that herbivore reduction, particularly when coupled with nutrient enrichment, favors non-calcifying, filamentous algae growth with high biomass production, which thoroughly outcompetes the encrusting (calcifying) algae that dominates in undisturbed conditions. These results suggest that the healthy reefs of the Central Red Sea may experience rapid shifts in benthic community composition with ensuing effects for biogeochemical cycles if

  4. In-Situ Effects of Simulated Overfishing and Eutrophication on Benthic Coral Reef Algae Growth, Succession, and Composition in the Central Red Sea.

    PubMed

    Jessen, Christian; Roder, Cornelia; Villa Lizcano, Javier Felipe; Voolstra, Christian R; Wild, Christian

    2013-01-01

    Overfishing and land-derived eutrophication are major local threats to coral reefs and may affect benthic communities, moving them from coral dominated reefs to algal dominated ones. The Central Red Sea is a highly under-investigated area, where healthy coral reefs are contending against intense coastal development. This in-situ study investigated both the independent and combined effects of manipulated inorganic nutrient enrichment (simulation of eutrophication) and herbivore exclosure (simulation of overfishing) on benthic algae development. Light-exposed and shaded terracotta tiles were positioned at an offshore patch reef close to Thuwal, Saudi Arabia and sampled over a period of 4 months. Findings revealed that nutrient enrichment alone affected neither algal dry mass nor algae-derived C or N production. In contrast, herbivore exclusion significantly increased algal dry mass up to 300-fold, and in conjunction with nutrient enrichment, this total increased to 500-fold. Though the increase in dry mass led to a 7 and 8-fold increase in organic C and N content, respectively, the algal C/N ratio (18±1) was significantly lowered in the combined treatment relative to controls (26±2). Furthermore, exclusion of herbivores significantly increased the relative abundance of filamentous algae on the light-exposed tiles and reduced crustose coralline algae and non-coralline red crusts on the shaded tiles. The combination of the herbivore exclusion and nutrient enrichment treatments pronounced these effects. The results of our study suggest that herbivore reduction, particularly when coupled with nutrient enrichment, favors non-calcifying, filamentous algae growth with high biomass production, which thoroughly outcompetes the encrusting (calcifying) algae that dominates in undisturbed conditions. These results suggest that the healthy reefs of the Central Red Sea may experience rapid shifts in benthic community composition with ensuing effects for biogeochemical cycles if

  5. Effect of Ocean acidification on growth, calcification and reproduction of calcifying and non-calcifying epibionts of brown algae

    NASA Astrophysics Data System (ADS)

    Saderne, V.; Wahl, M.

    2012-04-01

    Anthropogenic emissions of CO2 are leading to an acidification of the oceans of 0.4 pH units in the course of this century according to the more severe model scenarios. The excess of CO2 could notably affect the benthic communities of calcifiers and macrophytes in different aspects (photosynthesis, respiration and calcification). Seaweeds are one of the key species of nearshore benthic ecosystems of the Baltic Sea. They are the substratum of several fouling epibionts like bryozoans and tubeworms. Most of those species are bearing calcified structures and could therefore be potentially impacted by the seawater pCO2. On the other hand, the biological activity of the host may substantially modulate the pH and pCO2 conditions in the boundary layer where the epibionts live. The aim of the present study was to test the sensitivity of seaweed macrofouling communities to higher pCO2 concentration. Fragments of macroalgae Fucus serratus bearing the calcifiers Spirorbis spirorbis (Annelida) and Electra pilosa (Bryozoa) and the non-calcifier Alcyonidium gelatinosum (Bryozoa) were maintained for 30 days under three pCO2: natural 460 ± 59 µatm and enriched 1193 ± 166 µatm and 3150 ± 446 µatm. Our study showed a significant reduction of growth rates and reproduction of Spirorbis individuals at the highest pCO2. Tubeworms Juveniles exhibited enhanced calcification of 40 % when in the light compare to dark, presumably due to effect of photosynthetic and respiratory activities of the host alga. Electra colonies showed significantly improved growth rates at 1193 µatm. The overall net dissolution of the communities was significantly higher at 3150 µatm. No effect on Alcyonidium colonies growth rates was observed. Those results suggest a remarkable resistance of the algal macro-epibiontic communities to the most elevated pCO2 predicted for 2100 for open ocean (~1000 µatm) conditions. Concerns remains with regards to higher pCO2 possibly found in the future Baltic Sea.

  6. Mineral and non-carbon nutrient utilization and recovery during sequential phototrophic-heterotrophic growth of lipid-rich algae.

    PubMed

    Bohutskyi, Pavlo; Liu, Kexin; Kessler, Ben A; Kula, Thomas; Hong, Yongseok; Bouwer, Edward J; Betenbaugh, Michael J; Allnutt, F C Thomas

    2014-06-01

    A critical factor in implementing microalgal biofuels for mass production is the nutrient requirements. The current study investigated the fate of macro- and micronutrients and their availability in a sequential phototrophic-heterotrophic production process for the lipid rich microalga Auxenochlorella protothecoides. More than 99 % (by weight) of overall process nutrients were supplied during the initial photoautotrophic stage reflecting its significantly larger volume. Under photoautotrophic growth conditions only 9-35 % of supplied Mn, S, Fe, N, Mg, and Cu and less than 5 % of P, Mo, Co, B, Zn, and Ca were consumed by the algae. The rest of these nutrients remain in the spent growth media during the culture concentration-down from an 800 L phototrophic pond to a 5 L heterotrophic fermenter. In contrast, Zn, Mo, Mn, Mg, Ca, and N were exhausted (90-99 % removal) during the first 25 h of the heterotrophic growth stage. The depletion of these key nutrients may have ultimately limited the final biomass density and/or lipid productivity achieved. Approximately 10-20 % of the total supplied S, Mn, Fe, N, and Cu and 5 % of Ca and Zn were assimilated into algal biomass. Several elements including N, P, Mn, B, Cu, Ca, Mg, S, and Fe were released back into the liquid phase by anaerobic digestion (AD) of the residual biomass after lipid extraction. The nutrients recovered from the AD effluent and remaining in the spent medium should be recycled or their initial concentration to the phototrophic stage decreased to enhance process economics and sustainability for future commercialization of algal-derived biofuels. PMID:24839256

  7. Hydroxyapatite Growth Inhibition Effect of Pellicle Statherin Peptides.

    PubMed

    Xiao, Y; Karttunen, M; Jalkanen, J; Mussi, M C M; Liao, Y; Grohe, B; Lagugné-Labarthet, F; Siqueira, W L

    2015-08-01

    In our recent studies, we have shown that in vivo-acquired enamel pellicle is a sophisticated biological structure containing a significant portion of naturally occurring salivary peptides. From a functional aspect, the identification of peptides in the acquired enamel pellicle is of interest because many salivary proteins exhibit functional domains that maintain the activities of the native protein. Among the in vivo-acquired enamel pellicle peptides that have been newly identified, 5 peptides are derived from statherin. Here, we assessed the ability of these statherin pellicle peptides to inhibit hydroxyapatite crystal growth. In addition, atomistic molecular dynamics (MD) simulations were performed to better understand the underlying physical mechanisms of hydroxyapatite growth inhibition. A microplate colorimetric assay was used to quantify hydroxyapatite growth. Statherin protein, 5 statherin-derived peptides, and a peptide lacking phosphate at residues 2 and 3 were analyzed. Statherin peptide phosphorylated on residues 2 and 3 indicated a significant inhibitory effect when compared with the 5 other peptides (P < 0.05). MD simulations showed a strong affinity and fast adsorption to hydroxyapatite for phosphopeptides, whereas unphosphorylated peptides interacted weakly with the hydroxyapatite. Our data suggest that the presence of a covalently linked phosphate group (at residues 2 and 3) in statherin peptides modulates the effect of hydroxyapatite growth inhibition. This study provides a mechanism to account for the composition and function of acquired enamel pellicle statherin peptides that will contribute as a base for the development of biologically stable and functional synthetic peptides for therapeutic use against dental caries and/or periodontal disease. PMID:26116492

  8. Zinc toxicity to the alga Pseudokirchneriella subcapitata decreases under phosphate limiting growth conditions.

    PubMed

    Gao, C; De Schamphelaere, K A C; Smolders, E

    2016-04-01

    Previous studies have suggested that phosphorus (P) deficiency can increase the sensitivity of microalgae to toxic trace metals, potentially due to reduced metal detoxification at low cell P quota. The existing evidence is, however, inconsistent. This study was set up to determine the combined effects of zinc (Zn) and P supplies on Zn and P bioaccumulation and growth of the green microalgae Pseudokirchneriella subcapitata. Zinc toxicity was investigated in (i) a 24h growth rate assay with cells varying in initial cell P quota (0.5-1.7% P on cell dry weight) with no supplemental P during Zn exposure (Expt. 1) and in (ii) a 48h growth assay initiated with cells at the end of a 14-days steady state culture at three P addition rates (RARs) between 0.8 and 1.6day(-1) (Expt.2). The solution Zn concentrations required to reduce final cell density by 10% relative to control (EbC10) were 5-fold (Expt.1) or 2-fold (Expt.2) lower at the highest P supply than at the lowest P supply, i.e. Zn was more toxic at higher P supply, in contrast with the suggestions from previous studies. Cell P quota increased with increasing Zn in the exposure solution (Expt.2), thereby partially overcoming P deficiency under moderate Zn toxicity compared to low Zn exposure. Similarly, cell Zn increased with increasing P supply, potentially induced by Zn-P complexation or precipitation inside the cell. A dynamic growth model accounting for effects of external Zn and internal P on the specific growth rate was calibrated to all data. This model shows that the effect of solution Zn on specific growth rate (ErC50) was statistically unaffected by cell P quota. In contrast, this model predicts that the EbC10 (i.e. EC10 based on cell numbers) varies with P supply because cell P depends on external P and Zn. Moreover, scenario analysis predicts even contrasting trends of the EbC10 with increasing P supply depending on the duration of the growth assay and the P supply scenario. Our data at two experimental

  9. Transcriptional analysis of cell growth and morphogenesis in the unicellular green alga Micrasterias (Streptophyta), with emphasis on the role of expansin

    PubMed Central

    2011-01-01

    Background Streptophyte green algae share several characteristics of cell growth and cell wall formation with their relatives, the embryophytic land plants. The multilobed cell wall of Micrasterias denticulata that rebuilds symmetrically after cell division and consists of pectin and cellulose, makes this unicellular streptophyte alga an interesting model system to study the molecular controls on cell shape and cell wall formation in green plants. Results Genome-wide transcript expression profiling of synchronously growing cells identified 107 genes of which the expression correlated with the growth phase. Four transcripts showed high similarity to expansins that had not been examined previously in green algae. Phylogenetic analysis suggests that these genes are most closely related to the plant EXPANSIN A family, although their domain organization is very divergent. A GFP-tagged version of the expansin-resembling protein MdEXP2 localized to the cell wall and in Golgi-derived vesicles. Overexpression phenotypes ranged from lobe elongation to loss of growth polarity and planarity. These results indicate that MdEXP2 can alter the cell wall structure and, thus, might have a function related to that of land plant expansins during cell morphogenesis. Conclusions Our study demonstrates the potential of M. denticulata as a unicellular model system, in which cell growth mechanisms have been discovered similar to those in land plants. Additionally, evidence is provided that the evolutionary origins of many cell wall components and regulatory genes in embryophytes precede the colonization of land. PMID:21943227

  10. Phytotoxicity of nanoparticles: inhibition of seed germination and root growth.

    PubMed

    Lin, Daohui; Xing, Baoshan

    2007-11-01

    Plants need to be included to develop a comprehensive toxicity profile for nanoparticles. Effects of five types of nanoparticles (multi-walled carbon nanotube, aluminum, alumina, zinc, and zinc oxide) on seed germination and root growth of six higher plant species (radish, rape, ryegrass, lettuce, corn, and cucumber) were investigated. Seed germination was not affected except for the inhibition of nanoscale zinc (nano-Zn) on ryegrass and zinc oxide (nano-ZnO) on corn at 2000 mg/L. Inhibition on root growth varied greatly among nanoparticles and plants. Suspensions of 2000 mg/L nano-Zn or nano-ZnO practically terminated root elongation of the tested plant species. Fifty percent inhibitory concentrations (IC50) of nano-Zn and nano-ZnO were estimated to be near 50mg/L for radish, and about 20mg/L for rape and ryegrass. The inhibition occurred during the seed incubation process rather than seed soaking stage. These results are significant in terms of use and disposal of engineered nanoparticles. PMID:17374428

  11. Growth inhibition by tyrosine kinase inhibitors in mesothelioma cell lines.

    PubMed

    Nutt, Joyce E; O'Toole, Kieran; Gonzalez, David; Lunec, John

    2009-06-01

    Clinical outcome following chemotherapy for malignant pleural mesothelioma is poor and improvements are needed. This preclinical study investigates the effect of five tyrosine kinase inhibitors (PTK787, ZD6474, ZD1839, SU6668 and SU11248) on the growth of three mesothelioma cell lines (NCI H226, NCI H28 and MSTO 211H), the presence of growth factor receptors and inhibition of their downstream signalling pathways. GI50 values were determined: ZD6474 and SU11248, mainly VEGFR2 inhibitors, gave the lowest GI50 across all cell lines (3.5-6.9 microM) whereas ZD1839 gave a GI50 in this range only in H28 cells. All cell lines were positive for EGFR, but only H226 cells were positive for VEGFR2 by Western blotting. ZD6474 and ZD1839 inhibited EGF-induced phosphorylation of EGFR, AKT and ERK, whereas VEGF-induced phosphorylation of VEGFR2 was completely inhibited with 0.1 microM SU11248. VEGFR2 was detected in tumour samples by immunohistochemistry. VEGFR2 tyrosine kinase inhibitors warrant further investigation in mesothelioma. PMID:19318229

  12. Effect of petroleum hydrocarbons on algae

    SciTech Connect

    Bhadauria, S. ); Sengar, R.M.S. ); Mittal, S.; Bhattacharjee, S. )

    1992-01-01

    Algal species (65) were isolated from oil refinery effluent. Twenty-five of these species were cultured in Benecke's medium in a growth chamber, along with controls. Retardation in algal growth, inhibition in algal photosynthesis, and discoloration was observed in petroleum enriched medium. Few forms, viz. Cyclotella sp., Cosmarium sp., and Merismopedia sp. could not survive. The lag phase lengthened by several days and slope of exponential phase was also depressed. Chlamydomonas sp., Scenedesmus sp., Ankistrodesmus sp., Nitzschia sp. and Navicula sp. were comparatively susceptible to petroleum. Depression in carbon fixation, cell numbers, and total dry algal mass was noticeable, showing toxicity to both diatoms and green algae.

  13. The parasitic chytrid, Zygorhizidium, facilitates the growth of the cladoceran zooplankter, Daphnia, in cultures of the inedible alga, Asterionella

    PubMed Central

    Kagami, Maiko; von Elert, Eric; Ibelings, Bas W; de Bruin, Arnout; Van Donk, Ellen

    2007-01-01

    In food-web studies, parasites are often ignored owing to their insignificant biomass. We provide evidence that parasites may affect trophic transfer in aquatic food webs. Many phytoplankton species are susceptible to parasitic fungi (chytrids). Chytrid infections of diatoms in lakes may reach epidemic proportions during diatom spring blooms, so that numerous free-swimming fungal zoospores (2–3 μm in diameter) are produced. Analysis shows that these zoospores are rich in polyunsaturated fatty acids and sterols (particularly cholesterol), which indicates that they provide excellent food for zooplankters such as Daphnia. In life-table experiments using the large diatom Asterionella formosa as food, Daphnia growth increased significantly in treatments where a parasite was present. By grazing on the zoospores, Daphnia acquired important supplementary nutrients and were able to grow. When large inedible algae are infected by parasites, nutrients within the algal cells are consumed by these chytrids, some of which, in turn, are grazed by Daphnia. Thus, chytrids transfer energy and nutrients from their hosts to zooplankton. This study suggests that parasitic fungi alter trophic relationships in freshwater ecosystems and may be the important components in shaping the community and the food-web dynamics of lakes. PMID:17439852

  14. Control of ambient pH on growth and stable isotopes in phytoplanktonic calcifying algae

    NASA Astrophysics Data System (ADS)

    Hermoso, Michaël.

    2015-08-01

    The present work examines the relationship between pH-induced changes in growth and stable isotopic composition of coccolith calcite in two coccolithophore species with a geological perspective. These species (Gephyrocapsa oceanica and Coccolithus pelagicus) with differing physiologies and vital effects possess a growth optimum corresponding to average pH of surface seawater in the geological period during their first known occurrence. The "ancestral" C. pelagicus has much wider pH tolerance in terms of growth rates than the more recently evolved G. oceanica. Diminished growth rates are explained by the challenge of proton translocation into the extracellular environment at low pH and enhanced aqueous CO2 limitation at high pH. Reducing the cell dynamics in this way leads to a lower degree of oxygen isotopic disequilibrium in G. oceanica. In contrast, the slower growing species C. pelagicus, which typically precipitates near-equilibrium calcite, does not show any modulation of oxygen isotope signals with changing pH. Overall, carbon and oxygen isotope compositions are best explained by the degree of utilization of the internal dissolved inorganic carbon (DIC) pool and the dynamics of isotopic reequilibration inside the cell. Thus, the "carbonate ion effect" may not apply to coccolithophores. This difference with foraminifera can be traced to different modes of DIC incorporation into these two distinct biomineralizing organisms. From a geological perspective, these findings have implications for refining the use of oxygen isotopes to infer more reliable sea surface temperatures (SSTs) from fossil carbonates and contribute to a better understanding of how climate-relevant parameters are recorded in the sedimentary archive.

  15. Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth

    PubMed Central

    Wang, Jin Dao; Chen, Xiao Ying; Ji, Ke Wei; Tao, Feng

    2016-01-01

    Bruton’s tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer. PMID:27508020

  16. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth

    PubMed Central

    Harel, Sivan; Higgins, Claire A.; Cerise, Jane E.; Dai, Zhenpeng; Chen, James C.; Clynes, Raphael; Christiano, Angela M.

    2015-01-01

    Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells. PMID:26601320

  17. Prolonged cyclic strain inhibits human endothelial cell growth.

    PubMed

    Peyton, Kelly J; Liu, Xiao-ming; Durante, William

    2016-01-01

    The vascular endothelium is continuously exposed to cyclic mechanical strain due to the periodic change in vessel diameter as a result of pulsatile blood flow. Since emerging evidence indicates the cyclic strain plays an integral role in regulating endothelial cell function, the present study determined whether application of a physiologic regimen of cyclic strain (6% at 1 hertz) influences the proliferation of human arterial endothelial cells. Prolonged exposure of human dermal microvascular or human aortic endothelial cells to cyclic strain for up to 7 days resulted in a marked decrease in cell growth. The strain-mediated anti-proliferative effect was associated with the arrest of endothelial cells in the G2/M phase of the cell cycle, did not involve cell detachment or cytotoxicity, and was due to the induction of p21. Interestingly, the inhibition in endothelial cell growth was independent of the strain regimen since prolonged application of constant or intermittent 6% strain was also able to block endothelial cell proliferation. The ability of chronic physiologic cyclic strain to inhibit endothelial cell growth represents a previously unrecognized mechanism by which hemodynamic forces maintain these cells in a quiescent, non-proliferative state. PMID:26709656

  18. Pharmacologic inhibition of JAK-STAT signaling promotes hair growth.

    PubMed

    Harel, Sivan; Higgins, Claire A; Cerise, Jane E; Dai, Zhenpeng; Chen, James C; Clynes, Raphael; Christiano, Angela M

    2015-10-01

    Several forms of hair loss in humans are characterized by the inability of hair follicles to enter the growth phase (anagen) of the hair cycle after being arrested in the resting phase (telogen). Current pharmacologic therapies have been largely unsuccessful in targeting pathways that can be selectively modulated to induce entry into anagen. We show that topical treatment of mouse and human skin with small-molecule inhibitors of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway results in rapid onset of anagen and subsequent hair growth. We show that JAK inhibition regulates the activation of key hair follicle populations such as the hair germ and improves the inductivity of cultured human dermal papilla cells by controlling a molecular signature enriched in intact, fully inductive dermal papillae. Our findings open new avenues for exploration of JAK-STAT inhibition for promotion of hair growth and highlight the role of this pathway in regulating the activation of hair follicle stem cells. PMID:26601320

  19. Towards an organic palaeosalinity proxy: the effect of salinity, growth rate and growth phase on the hydrogen isotopic composition of alkenones produced by haptophyte algae

    NASA Astrophysics Data System (ADS)

    Chivall, David; M'Boule, Daniela; Schouten, Stefan; Sinninghe Damsté, Jaap S.; van der Meer, Marcel T. J.

    2013-04-01

    Palaeosalinity is one of the most important oceanographic parameters which currently cannot be quantified with reasonable accuracy from sedimentary records. Schouten et al.1 established that the fractionation of hydrogen isotopes between growth water and alkenones produced by the haptophyte algae Emiliania huxleyi and Gephyrocapsa oceanica is salinity dependent. As such, the δD values of alkenones recovered from sediment cores can be used to reconstruct variations in palaeo- sea surface salinity.2 However, to accurately determine absolute palaeosalinity requires a better constraining of the relationship between this hydrogen fractionation, salinity and other parameters such as growth rate and growth phase. Here, we present results from our ongoing work to constrain the relationship between the fractionation factor αalkenone-water, salinity, growth rate and growth phase for the major alkenone-producing haptophytes. In batch cultures of different strains of the open-ocean haptophyte E. huxleyi sampled during the exponential growth phase, αC37alkenone-growthwater increases by between 0.0022 and 0.0033 per unit increase in salinity. A similar relationship is observed in batch cultures of the coastal haptophyte Isochrysis galbana, where α increases with each unit of salinity by 0.0019 - slightly less than for E. huxleyi. However, absolute αC37alkenone-growthwater values vary strongly between species suggesting that species composition has a strong impact on the δD value of alkenones. The fractionation factor for alkenones produced by batch cultures of I. galbana is affected by growth phase: the rate of change of αC37alkenone-growthwater with each unit of salinity decreases from 0.0019 in the exponential phase to 0.0010 during the stationary phase. We also show the effect of varying growth rate over the range 0.2-0.8 day-1 on the fractionation factor for alkenones produced by E. huxleyi grown in continuous culture. These data show that alkenone δD can be used to

  20. Meloxicam inhibits the growth of colorectal cancer cells.

    PubMed

    Goldman, A P; Williams, C S; Sheng, H; Lamps, L W; Williams, V P; Pairet, M; Morrow, J D; DuBois, R N

    1998-12-01

    Cyclooxygenase-2 has been reported to play an important role in colorectal carcinogenesis. The effects of meloxicam (a COX-2 inhibitor) on the growth of two colon cancer cell lines that express COX-2 (HCA-7 and Moser-S) and a COX-2 negative cell line (HCT-116) were evaluated. The growth rate of these cells was measured following treatment with meloxicam. HCA-7 and Moser-S colony size were significantly reduced following treatment with meloxicam; however, there was no significant change in HCT-116 colony size with treatment. In vivo studies were performed to evaluate the effect of meloxicam on the growth of HCA-7 cells when xenografted into nude mice. We observed a 51% reduction in tumor size after 4 weeks of treatment. Analysis of COX-1 and COX-2 protein levels in HCA-7 tumor lysates revealed a slight decrease in COX-2 expression levels in tumors taken from mice treated with meloxicam and no detectable COX-1 expression. Here we report that meloxicam significantly inhibited HCA-7 colony and tumor growth but had no effect on the growth of the COX-2 negative HCT-116 cells. PMID:9886578

  1. Structural effects of ionic liquids on microalgal growth inhibition and microbial degradation.

    PubMed

    Pham, Thi Phuong Thuy; Cho, Chul-Woong; Yun, Yeoung-Sang

    2016-03-01

    In the present study, we investigated structural effects of various ionic liquids (ILs) on microalgal growth inhibition and microbial biodegradability. For this, we tested pyridinium- and pyrrolidinium-based ILs with various alkyl chain lengths and bromide anion, and compared the toxicological effects with log EC50 values of imidazolium-based IL with the same alkyl chains and anion from literature. Comparing determined EC50 values of cationic moieties with the same alkyl chain length, pyridinium-based ILs were found to be slightly more toxic towards the freshwater green alga, Pseudokirchneriella subcapitata, than a series of pyrrolidinium and imidazolium except to 1-octyl-3-methylimidazolium bromide. Concerning the biodegradation study of 12 ILs using the activated sludge microorganisms, the results showed that the pyridinium derivatives except to 1-propyl-3-methylpyridinium cation were degraded. Whereas in case of imidazolium- and pyrrolidinium-based compounds, only n-hexyl and n-octyl substituted cations were fully degraded but no significant biodegradation was observed for the short chains (three and four alkyl chains). PMID:26330315

  2. Inhibitory effects of soluble algae products (SAP) released by Scenedesmus sp. LX1 on its growth and lipid production.

    PubMed

    Zhang, Tian-Yuan; Yu, Yin; Wu, Yin-Hu; Hu, Hong-Ying

    2013-10-01

    Soluble algal products (SAP) accumulated in culture medium via water reuse may affect the growth of microalga during the cultivation. Scenedesmus sp. LX1, a freshwater microalga, was used in this study to investigate the effect of SAP on growth and lipid production of microalga. Under the SAP concentrations of 6.4-25.8 mg L(-1), maximum algal density (K) and maximum growth rate (Rmax) of Scenedesmus sp. LX1 were decreased by 50-80% and 35-70% compared with the control group, respectively. The effect of SAP on lipid accumulation of Scenedesmus sp. LX1 was non-significant. According to hydrophilic-hydrophobic and acid-base properties, SAP was fractionized into six fractions. All of the fractions could inhibit the growth of Scenedesmus sp. LX1. Organic bases (HIB, HOB) and hydrophilic acids (HIA) showed the strongest inhibition. HIA could also decrease the lipid content of Scenedesmus sp. LX1 by 59.2%. As the inhibitory effect, SAP should be seriously treated before water reuse. PMID:23982061

  3. Multiple effects of Bacillus amyloliquefaciens volatile compounds: plant growth promotion and growth inhibition of phytopathogens.

    PubMed

    Asari, Shashidar; Matzén, Staffan; Petersen, Mikael Agerlin; Bejai, Sarosh; Meijer, Johan

    2016-06-01

    Biotic interactions through volatile organic compounds (VOC) are frequent in nature. This investigation aimed to study the role of ITALIC! BacillusVOC for the beneficial effects on plants observed as improved growth and pathogen control. Four ITALIC! Bacillus amyloliquefacienssubsp. ITALIC! plantarumstrains were screened for VOC effects on ITALIC! Arabidopsis thalianaCol-0 seedlings and ITALIC! Brassicafungal phytopathogens. VOC from all four ITALIC! Bacillusstrains could promote growth of ITALIC! Arabidopsisplants resulting in increased shoot biomass but the effects were dependent on the growth medium. Dose response studies with UCMB5113 on MS agar with or without root exudates showed significant plant growth promotion even at low levels of bacteria. ITALIC! BacillusVOC antagonized growth of several fungal pathogens ITALIC! in vitro However, the plant growth promotion efficacy and fungal inhibition potency varied among the ITALIC! Bacillusstrains. VOC inhibition of several phytopathogens indicated efficient microbial antagonism supporting high rhizosphere competence of the ITALIC! Bacillusstrains. GC-MS analysis identified several VOC structures where the profiles differed depending on the growth medium. The ability of ITALIC! Bacillusstrains to produce both volatile and soluble compounds for plant growth promotion and disease biocontrol provides examples of rhizosphere microbes as an important ecosystem service with high potential to support sustainable crop production. PMID:27053756

  4. Kinetic model of particle-inhibited grain growth

    NASA Astrophysics Data System (ADS)

    Thompson, Gary Scott

    The effects of second phase particles on matrix grain growth kinetics were investigated using Al2O3-SiC as a model system. In particular, the validity of the conclusion drawn from a previous kinetic analysis that the kinetics of particle-inhibited grain growth in Al2 O3-SiC samples with an intermediate volume fraction of second phase could be well quantified by a modified-Zener model was investigated. A critical analysis of assumptions made during the previous kinetic analysis revealed oversimplifications which affect the validity of the conclusion. Specifically, the degree of interaction between particles and grain boundaries was assumed to be independent of the mean second phase particle size and size distribution. In contrast, current measurements indicate that the degree of interaction in Al2O3-SiC is dependent on these parameters. An improved kinetic model for particle-inhibited grain growth in Al 2O3-SiC was developed using a modified-Zener approach. The comparison of model predictions with experimental grain growth data indicated that significant discrepancies (as much as 4--5 orders of magnitude) existed. Based on this, it was concluded that particles had a much more significant effect on grain growth kinetics than that caused by a simple reduction of the boundary driving force due to the removal of boundary area. Consequently, it was also concluded that the conclusion drawn from the earlier kinetic analysis regarding the validity of a modified-Zener model was incorrect. Discrepancies between model and experiment were found to be the result of a significant decrease in experimental growth rate constant not predicted by the model. Possible physical mechanisms for such a decrease were investigated. The investigation of a small amount of SiO2 on grain growth in Al2O3 indicated that the decrease was not the result of a decrease in grain boundary mobility due to impurity contamination by particles. By process of elimination and based on previous observations

  5. Effect of centrifugation on water recycling and algal growth to enable algae biodiesel production.

    PubMed

    Igou, Thomas; Van Ginkel, Steven W; Penalver-Argueso, Patricia; Fu, Hao; Doi, Shusuke; Narode, Asmita; Cheruvu, Sarasija; Zhang, Qian; Hassan, Fariha; Woodruff, Frazier; Chen, Yongsheng

    2014-12-01

    The latest research shows that algal biofuels, at the production levels mandated in the Energy Independence and Security Act of 2007, will place significant demands on water and compete with agriculture meant for food production. Thus, there is a great need to recycle water while producing algal biofuels. This study shows that when using a synthetic medium, soluble algal products, bacteria, and other inhibitors can be removed by centrifugation and enable water recycling. Average water recovery reached 84% and water could be recycled at least 10 times without reducing algal growth. PMID:25654935

  6. DNA Walker-Regulated Cancer Cell Growth Inhibition.

    PubMed

    Li, Feiran; Cha, Tae-Gon; Pan, Jing; Ozcelikkale, Altug; Han, Bumsoo; Choi, Jong Hyun

    2016-06-16

    We demonstrate a DNAzyme-based walker system as a controlled oligonucleotide drug AS1411 release platform for breast cancer treatment. In this system, AS1411 strands are released from fuel strands as a walker moves along its carbon nanotube track. The release rate and amount of anticancer oligonucleotides are controlled by the walker operation. With a walker system embedded within the collagen extracellular matrix, we show that this drug release system can be used for in situ cancer cell growth inhibition. PMID:27059426

  7. Factors determining growth and vertical distribution of planktonic algae in extremely acidic mining lakes (pH 2.7)

    NASA Astrophysics Data System (ADS)

    Bissinger, Vera

    2003-04-01

    In this thesis, I investigated the factors influencing the growth and vertical distribution of planktonic algae in extremely acidic mining lakes (pH 2-3). In the focal study site, Lake 111 (pH 2.7; Lusatia, Germany), the chrysophyte, Ochromonas sp., dominates in the upper water strata and the chlorophyte, Chlamydomonas sp., in the deeper strata, forming a pronounced deep chlorophyll maximum (DCM). Inorganic carbon (IC) limitation influenced the phototrophic growth of Chlamydomonas sp. in the upper water strata. Conversely, in deeper strata, light limited its phototrophic growth. When compared with published data for algae from neutral lakes, Chlamydomonas sp. from Lake 111 exhibited a lower maximum growth rate, an enhanced compensation point and higher dark respiration rates, suggesting higher metabolic costs due to the extreme physico-chemical conditions. The photosynthetic performance of Chlamydomonas sp. decreased in high-light-adapted cells when IC limited. In addition, the minimal phosphorus (P) cell quota was suggestive of a higher P requirement under IC limitation. Subsequently, it was shown that Chlamydomonas sp. was a mixotroph, able to enhance its growth rate by taking up dissolved organic carbon (DOC) via osmotrophy. Therefore, it could survive in deeper water strata where DOC concentrations were higher and light limited. However, neither IC limitation, P availability nor in situ DOC concentrations (bottom-up control) could fully explain the vertical distribution of Chlamydomonas sp. in Lake 111. Conversely, when a novel approach was adopted, the grazing influence of the phagotrophic phototroph, Ochromonas sp., was found to exert top-down control on its prey (Chlamydomonas sp.) reducing prey abundance in the upper water strata. This, coupled with the fact that Chlamydomonas sp. uses DOC for growth, leads to a pronounced accumulation of Chlamydomonas sp. cells at depth; an apparent DCM. Therefore, grazing appears to be the main factor influencing the

  8. Piperlongumine inhibits lung tumor growth via inhibition of nuclear factor kappa B signaling pathway.

    PubMed

    Zheng, Jie; Son, Dong Ju; Gu, Sun Mi; Woo, Ju Rang; Ham, Young Wan; Lee, Hee Pom; Kim, Wun Jae; Jung, Jae Kyung; Hong, Jin Tae

    2016-01-01

    Piperlongumine has anti-cancer activity in numerous cancer cell lines via various signaling pathways. But there has been no study regarding the mechanisms of PL on the lung cancer yet. Thus, we evaluated the anti-cancer effects and possible mechanisms of PL on non-small cell lung cancer (NSCLC) cells in vivo and in vitro. Our findings showed that PL induced apoptotic cell death and suppressed the DNA binding activity of NF-κB in a concentration dependent manner (0-15 μM) in NSCLC cells. Docking model and pull down assay showed that PL directly binds to the DNA binding site of nuclear factor-κB (NF-κB) p50 subunit, and surface plasmon resonance (SPR) analysis showed that PL binds to p50 concentration-dependently. Moreover, co-treatment of PL with NF-κB inhibitor phenylarsine oxide (0.1 μM) or p50 siRNA (100 nM) augmented PL-induced inhibitory effect on cell growth and activation of Fas and DR4. Notably, co-treatment of PL with p50 mutant plasmid (C62S) partially abolished PL-induced cell growth inhibition and decreased the enhanced expression of Fas and DR4. In xenograft mice model, PL (2.5-5 mg/kg) suppressed tumor growth of NSCLC dose-dependently. Therefore, these results indicated that PL could inhibit lung cancer cell growth via inhibition of NF-κB signaling pathway in vitro and in vivo. PMID:27198178

  9. Piperlongumine inhibits lung tumor growth via inhibition of nuclear factor kappa B signaling pathway

    PubMed Central

    Zheng, Jie; Son, Dong Ju; Gu, Sun Mi; Woo, Ju Rang; Ham, Young Wan; Lee, Hee Pom; Kim, Wun Jae; Jung, Jae Kyung; Hong, Jin Tae

    2016-01-01

    Piperlongumine has anti-cancer activity in numerous cancer cell lines via various signaling pathways. But there has been no study regarding the mechanisms of PL on the lung cancer yet. Thus, we evaluated the anti-cancer effects and possible mechanisms of PL on non-small cell lung cancer (NSCLC) cells in vivo and in vitro. Our findings showed that PL induced apoptotic cell death and suppressed the DNA binding activity of NF-κB in a concentration dependent manner (0–15 μM) in NSCLC cells. Docking model and pull down assay showed that PL directly binds to the DNA binding site of nuclear factor-κB (NF-κB) p50 subunit, and surface plasmon resonance (SPR) analysis showed that PL binds to p50 concentration-dependently. Moreover, co-treatment of PL with NF-κB inhibitor phenylarsine oxide (0.1 μM) or p50 siRNA (100 nM) augmented PL-induced inhibitory effect on cell growth and activation of Fas and DR4. Notably, co-treatment of PL with p50 mutant plasmid (C62S) partially abolished PL-induced cell growth inhibition and decreased the enhanced expression of Fas and DR4. In xenograft mice model, PL (2.5–5 mg/kg) suppressed tumor growth of NSCLC dose-dependently. Therefore, these results indicated that PL could inhibit lung cancer cell growth via inhibition of NF-κB signaling pathway in vitro and in vivo. PMID:27198178

  10. Entry Inhibition of Influenza Viruses with High Mannose Binding Lectin ESA-2 from the Red Alga Eucheuma serra through the Recognition of Viral Hemagglutinin

    PubMed Central

    Sato, Yuichiro; Morimoto, Kinjiro; Kubo, Takanori; Sakaguchi, Takemasa; Nishizono, Akira; Hirayama, Makoto; Hori, Kanji

    2015-01-01

    Lectin sensitivity of the recent pandemic influenza A virus (H1N1-2009) was screened for 12 lectins with various carbohydrate specificity by a neutral red dye uptake assay with MDCK cells. Among them, a high mannose (HM)-binding anti-HIV lectin, ESA-2 from the red alga Eucheuma serra, showed the highest inhibition against infection with an EC50 of 12.4 nM. Moreover, ESA-2 exhibited a wide range of antiviral spectrum against various influenza strains with EC50s of pico molar to low nanomolar levels. Besides ESA-2, HM-binding plant lectin ConA, fucose-binding lectins such as fungal AOL from Aspergillus oryzae and AAL from Aleuria aurantia were active against H1N1-2009, but the potency of inhibition was of less magnitude compared with ESA-2. Direct interaction between ESA-2 and a viral envelope glycoprotein, hemagglutinin (HA), was demonstrated by ELISA assay. This interaction was effectively suppressed by glycoproteins bearing HM-glycans, indicating that ESA-2 binds to the HA of influenza virus through HM-glycans. Upon treatment with ESA-2, no viral antigens were detected in the host cells, indicating that ESA-2 inhibited the initial steps of virus entry into the cells. ESA-2 would thus be useful as a novel microbicide to prevent penetration of viruses such as HIV and influenza viruses to the host cells. PMID:26035023

  11. Entry Inhibition of Influenza Viruses with High Mannose Binding Lectin ESA-2 from the Red Alga Eucheuma serra through the Recognition of Viral Hemagglutinin.

    PubMed

    Sato, Yuichiro; Morimoto, Kinjiro; Kubo, Takanori; Sakaguchi, Takemasa; Nishizono, Akira; Hirayama, Makoto; Hori, Kanji

    2015-06-01

    Lectin sensitivity of the recent pandemic influenza A virus (H1N1-2009) was screened for 12 lectins with various carbohydrate specificity by a neutral red dye uptake assay with MDCK cells. Among them, a high mannose (HM)-binding anti-HIV lectin, ESA-2 from the red alga Eucheuma serra, showed the highest inhibition against infection with an EC50 of 12.4 nM. Moreover, ESA-2 exhibited a wide range of antiviral spectrum against various influenza strains with EC50s of pico molar to low nanomolar levels. Besides ESA-2, HM-binding plant lectin ConA, fucose-binding lectins such as fungal AOL from Aspergillus oryzae and AAL from Aleuria aurantia were active against H1N1-2009, but the potency of inhibition was of less magnitude compared with ESA-2. Direct interaction between ESA-2 and a viral envelope glycoprotein, hemagglutinin (HA), was demonstrated by ELISA assay. This interaction was effectively suppressed by glycoproteins bearing HM-glycans, indicating that ESA-2 binds to the HA of influenza virus through HM-glycans. Upon treatment with ESA-2, no viral antigens were detected in the host cells, indicating that ESA-2 inhibited the initial steps of virus entry into the cells. ESA-2 would thus be useful as a novel microbicide to prevent penetration of viruses such as HIV and influenza viruses to the host cells. PMID:26035023

  12. Growth inhibition of the cyanobacterium Microcystis aeruginosa and degradation of its microcystin toxins by the fungus Trichoderma citrinoviride.

    PubMed

    Mohamed, Zakaria A; Hashem, Mohamed; Alamri, Saad A

    2014-08-01

    Harmful cyanobacterial blooms are recognized as a rapidly expanding global problem that threatens human and ecosystem health. Many bacterial strains have been reported as possible agents for inhibiting and controlling these blooms. However, such algicidal activity is largely unexplored for fungi. In this study, a fungal strain kkuf-0955, isolated from decayed cyanobacterial bloom was tested for its capability to inhibit phytoplankton species in batch cultures. The strain was identified as Trichoderma citrinoviride Based on its morphological characteristics and DNA sequence. Microcystis aeruginosa co-cultivated with living fungal mycelia rapidly decreased after one day of incubation, and all cells completely died and lysed after 2 days. The fungal filtrate of 5-day culture also exhibited an inhibitory effect on M. aeruginosa, and this inhibition increased with the amount of filtrate and incubation time. Conversely, green algae and diatoms have not been influenced by either living fungal mycelia or culture filtrate. Interestingly, the fungus was not only able to inhibit Microcystis growth but also degraded microcystin produced by this cyanobacterium. The toxins were completely degraded within 5 days of incubation with living fungal mycelia, but not significantly changed with fungal filtrate. This fungus could be a potential bioagent to selectively control Microcystis blooms and degrade microcystin toxins. PMID:24874888

  13. Mo polyoxometalate nanoparticles inhibit tumor growth and vascular endothelial growth factor induced angiogenesis

    NASA Astrophysics Data System (ADS)

    Zheng, Wenjing; Yang, Licong; Liu, Ying; Qin, Xiuying; Zhou, Yanhui; Zhou, Yunshan; Liu, Jie

    2014-06-01

    Tumor growth depends on angiogenesis, which can furnish the oxygen and nutrients that proliferate tumor cells. Thus, blocking angiogenesis can be an effective strategy to inhibit tumor growth. In this work, three typical nanoparticles based on polyoxometalates (POMs) have been prepared; we investigated their capability as antitumor and anti-angiogenesis agents. We found that Mo POM nanoparticles, especially complex 3, inhibited the growth of human hepatocellular liver carcinoma cells (HepG2) through cellular reactive oxygen species levels’ elevation and mitochondrial membrane potential damage. Complex 3 also suppressed the proliferation, migration, and tube formation of endothelial cells in vitro and chicken chorioallantoic membrane development ex vivo. Furthermore, western blot analysis of cell signaling molecules indicated that Mo POMs blocked the vascular endothelial growth factor receptor 2-mediated ERK1/2 and AKT signaling pathways in endothelial cells. Using transmission electron microscopy, we demonstrated their cellular uptake and localization within the cytoplasm of HepG2 cells. These results indicate that, owing to the extraordinary physical and chemical properties, Mo POM nanoparticles can significantly inhibit tumor growth and angiogenesis, which makes them potential drug candidates in anticancer and anti-angiogenesis therapies.

  14. Hypernegative Supercoiling Inhibits Growth by Causing RNA Degradation▿

    PubMed Central

    Baaklini, Imad; Usongo, Valentine; Nolent, Flora; Sanscartier, Patrick; Hraiky, Chadi; Drlica, Karl; Drolet, Marc

    2008-01-01

    Transcription-induced hypernegative supercoiling is a hallmark of Escherichia coli topoisomerase I (topA) mutants. However, its physiological significance has remained unclear. Temperature downshift of a mutant yielded transient growth arrest and a parallel increase in hypernegative supercoiling that was more severe with lower temperature. Both properties were alleviated by overexpression of RNase HI. While ribosomes in extracts showed normal activity when obtained during growth arrest, mRNA on ribosomes was reduced for fis and shorter for crp, polysomes were much less abundant relative to monosomes, and protein synthesis rate dropped, as did the ratio of large to small proteins. Altered processing and degradation of lacA and fis mRNA was also observed. These data are consistent with truncation of mRNA during growth arrest. These effects were not affected by a mutation in the gene encoding RNase E, indicating that this endonuclease is not involved in the abnormal mRNA processing. They were also unaffected by spectinomycin, an inhibitor of protein synthesis, which argued against induction of RNase activity. In vitro transcription revealed that R-loop formation is more extensive on hypernegatively supercoiled templates. These results allow us, for the first time, to present a model by which hypernegative supercoiling inhibits growth. In this model, the introduction of hypernegative supercoiling by gyrase facilitates degradation of nascent RNA; overproduction of RNase HI limits the accumulation of hypernegative supercoiling, thereby preventing extensive RNA degradation. PMID:18790862

  15. Hypernegative supercoiling inhibits growth by causing RNA degradation.

    PubMed

    Baaklini, Imad; Usongo, Valentine; Nolent, Flora; Sanscartier, Patrick; Hraiky, Chadi; Drlica, Karl; Drolet, Marc

    2008-11-01

    Transcription-induced hypernegative supercoiling is a hallmark of Escherichia coli topoisomerase I (topA) mutants. However, its physiological significance has remained unclear. Temperature downshift of a mutant yielded transient growth arrest and a parallel increase in hypernegative supercoiling that was more severe with lower temperature. Both properties were alleviated by overexpression of RNase HI. While ribosomes in extracts showed normal activity when obtained during growth arrest, mRNA on ribosomes was reduced for fis and shorter for crp, polysomes were much less abundant relative to monosomes, and protein synthesis rate dropped, as did the ratio of large to small proteins. Altered processing and degradation of lacA and fis mRNA was also observed. These data are consistent with truncation of mRNA during growth arrest. These effects were not affected by a mutation in the gene encoding RNase E, indicating that this endonuclease is not involved in the abnormal mRNA processing. They were also unaffected by spectinomycin, an inhibitor of protein synthesis, which argued against induction of RNase activity. In vitro transcription revealed that R-loop formation is more extensive on hypernegatively supercoiled templates. These results allow us, for the first time, to present a model by which hypernegative supercoiling inhibits growth. In this model, the introduction of hypernegative supercoiling by gyrase facilitates degradation of nascent RNA; overproduction of RNase HI limits the accumulation of hypernegative supercoiling, thereby preventing extensive RNA degradation. PMID:18790862

  16. Cinnamic acid increases lignin production and inhibits soybean root growth.

    PubMed

    Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth. PMID:23922685

  17. The Study of Algae

    ERIC Educational Resources Information Center

    Rushforth, Samuel R.

    1977-01-01

    Included in this introduction to the study of algae are drawings of commonly encountered freshwater algae, a summary of the importance of algae, descriptions of the seven major groups of algae, and techniques for collection and study of algae. (CS)

  18. RPA inhibition increases replication stress and suppresses tumor growth.

    PubMed

    Glanzer, Jason G; Liu, Shengqin; Wang, Ling; Mosel, Adam; Peng, Aimin; Oakley, Greg G

    2014-09-15

    The ATR/Chk1 pathway is a critical surveillance network that maintains genomic integrity during DNA replication by stabilizing the replication forks during normal replication to avoid replication stress. One of the many differences between normal cells and cancer cells is the amount of replication stress that occurs during replication. Cancer cells with activated oncogenes generate increased levels of replication stress. This creates an increased dependency on the ATR/Chk1 pathway in cancer cells and opens up an opportunity to preferentially kill cancer cells by inhibiting this pathway. In support of this idea, we have identified a small molecule termed HAMNO ((1Z)-1-[(2-hydroxyanilino)methylidene]naphthalen-2-one), a novel protein interaction inhibitor of replication protein A (RPA), a protein involved in the ATR/Chk1 pathway. HAMNO selectively binds the N-terminal domain of RPA70, effectively inhibiting critical RPA protein interactions that rely on this domain. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. By itself, HAMNO treatment creates DNA replication stress in cancer cells that are already experiencing replication stress, but not in normal cells, and it acts synergistically with etoposide to kill cancer cells in vitro and slow tumor growth in vivo. Thus, HAMNO illustrates how RPA inhibitors represent candidate therapeutics for cancer treatment, providing disease selectivity in cancer cells by targeting their differential response to replication stress. Cancer Res; 74(18); 5165-72. ©2014 AACR. PMID:25070753

  19. RPA Inhibition increases Replication Stress and Suppresses Tumor Growth

    PubMed Central

    Glanzer, Jason G.; Liu, Shengqin; Wang, Ling; Mosel, Adam; Peng, Aimin; Oakley, Greg G.

    2014-01-01

    The ATR/Chk1 pathway is a critical surveillance network that maintains genomic integrity during DNA replication by stabilizing the replication forks during normal replication to avoid replication stress. One of the many differences between normal cells and cancer cells is the amount of replication stress that occurs during replication. Cancer cells with activated oncogenes generate increased levels of replication stress. This creates an increased dependency on the ATR/Chk1 pathway in cancer cells and opens up an opportunity to preferentially kill cancer cells by inhibiting this pathway. In support of this idea, we have identified a small molecule termed HAMNO ((1Z)-1-[(2-hydroxyanilino)methylidene]naphthalen-2-one), a novel protein interaction inhibitor of replication protein A (RPA), a protein involved in the ATR/Chk1 pathway. HAMNO selectively binds the N-terminal domain of RPA70, effectively inhibiting critical RPA protein interactions which rely on this domain. HAMNO inhibits both ATR autophosphorylation and phosphorylation of RPA32 Ser33 by ATR. By itself, HAMNO treatment creates DNA replication stress in cancer cells that are already experiencing replication stress, but not in normal cells, and it acts synergistically with etoposide to kill cancer cells in vitro and slow tumor growth in vivo. Thus, HAMNO illustrates how RPA inhibitors represent candidate therapeutics for cancer treatment, providing disease selectivity in cancer cells by targeting their differential response to replication stress. PMID:25070753

  20. Micronutrient Requirements for Growth and Hydrocarbon Production in the Oil Producing Green Alga Botryococcus braunii (Chlorophyta)

    PubMed Central

    Song, Liang; Qin, Jian G.; Su, Shengqi; Xu, Jianhe; Clarke, Stephen; Shan, Yichu

    2012-01-01

    The requirements of micronutrients for biomass and hydrocarbon production in Botryococcus braunii UTEX 572 were studied using response surface methodology. The concentrations of four micronutrients (iron, manganese, molybdenum, and nickel) were manipulated to achieve the best performance of B. braunii in laboratory conditions. The responses of algal biomass and hydrocarbon to the concentration variations of the four micronutrients were estimated by a second order quadratic regression model. Genetic algorithm calculations showed that the optimal level of micronutrients for algal biomass were 0.266 µM iron, 0.707 µM manganese, 0.624 µM molybdenum and 3.38 µM nickel. The maximum hydrocarbon content could be achieved when the culture media contained 10.43 µM iron, 6.53 µM manganese, 0.012 µM molybdenum and 1.73 µM nickel. The validation through an independent test in a photobioreactor suggests that the modified media with optimised concentrations of trace elements can increase algal biomass by 34.5% and hydrocarbon by 27.4%. This study indicates that micronutrients play significant roles in regulating algal growth and hydrocarbon production, and the response surface methodology can be used to optimise the composition of culture medium in algal culture. PMID:22848502

  1. The green alga, Cladophora, promotes Escherichia coli growth and contamination of recreational waters in Lake Michigan

    USGS Publications Warehouse

    Heuvel, A.V.; McDermott, C.; Pillsbury, R.; Sandrin, T.; Kinzelman, J.; Ferguson, J.; Sadowsky, M.; Byappanahalli, M.; Whitman, R.; Kleinheinz, G.T.

    2010-01-01

    A linkage between Cladophora mats and exceedances of recreational water quality criteria has been suggested, but not directly studied. Th is study investigates the spatial and temporal association between Escherichia coli concentrations within and near Cladophora mats at two northwestern Lake Michigan beaches in Door County, Wisconsin. Escherichia coli concentrations in water underlying mats were significantly greater than surrounding water (p < 0.001). Below mat E. coli increased as the stranded mats persisted at the beach swash zone. Water adjacent to Cladophora mats had lower E. coli concentrations, but surpassed EPA swimming criteria the majority of sampling days. A signifi cant positive association was found between E. coli concentrations attached to Cladophora and in underlying water (p < 0.001). The attached E. coli likely acted as a reservoir for populating water underlying the mat. Fecal bacterial pathogens, however, could not be detected by microbiological culture methods either attached to mat biomass or in underlying water. Removal of Cladophora mats from beach areas may improve aesthetic and microbial water quality at affected beaches. These associations and potential natural growth of E. coli in bathing waters call into question the efficacy of using E. coli as a recreational water quality indicator of fecal contaminations. Copyright ?? 2010 by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America. All rights reserved.

  2. Specificity of growth inhibition of melanoma by 4-hydroxyanisole

    SciTech Connect

    Kulkarni, G.A.; Nathanson, L.

    1989-01-01

    An experimental study using human melanoma (NEL-MI), rat hepatoma (Fu5-5), and human kidney (293-31) cell lines was undertaken in order to evaluate the antitumor activity of 4-hydroxyanisole (4-OHA) in vitro. Prior reports have indicated highly specific antitumor activity of 4-OHA against melanoma cells in vitro. This specific antitumor activity has been proposed to be due to the oxidation of 4-OHA by tyrosinase to cytotoxic oxidation products. Dose-dependent cytotoxicity was observed when cells were cultured for 72 h in the presence of 4-OHA. At 100 microM, 4-OHA produced growth inhibition of 62%, 32%, and 55% in melanoma, hepatoma, and kidney cell lines, respectively. No effect was seen at 10 microM 4-OHA. 1,000 microM 4-OHA produced 100% kill. Tyrosinase activity was detected only in melanoma cells. The effect of 100 microM 4-OHA on the incorporation of 3H DNA precursors in melanoma, hepatoma, and kidney cells was also studied. Thymidine incorporation was inhibited in all three cell lines at the lowest cell density tested, with the greatest inhibition seen on melanoma cells. As cell density increased, the effect of 4-OHA on thymidine incorporation decreased. With respect to RNA synthesis, 4-OHA significantly reduced the incorporation of uridine in all three cell lines, with the greatest effect in melanoma cells. Cell density also affected the inhibition of uridine incorporation, but to a lesser extent than that observed on thymidine incorporation. The effect of 4-OHA on leucine incorporation was modest and uninfluenced by cell density. Thus, cytotoxicity of 4-OHA may involve two different mechanisms.

  3. The fate of glyphosate in water hyacinth and its physiological and biochemical influences on growth of algae

    SciTech Connect

    Tsai, Baolong.

    1989-01-01

    Absorption, translocation, distribution, exudation, and guttation of {sup 14}C-glyphosate in water hyacinth (Eichhornia crassipes) were studied. Glyphosphate entered the plant by foliage and solution treatment. Plants were harvested and separated into the following parts: treated leaf blade, treated leaf petiole, young leaf blade, young leaf petiole, old leak blade, old leaf petiole, and root. Each part was extracted with methanol. Treated leaves, which exist only in foliage treatment, were washed with water and chloroform to remove the glyphosate residues. All {sup 14}C counting was made by liquid scintillation spectrometry. Autoradiography was used to locate {sup 14}C-glyphosate after foliage treatment. Results indicated that glyphosate can be absorbed from the leaf surface and translocated rapidly through phloem tissues into the whole plant body. The roots of water hyacinth absorbed glyphosate without vertical transport. Guttation of glyphosate occurred in treated leaf tips. Exudation of glyphosate from roots of water hyacinth occurred within 8 hr after foliage treatment. Chlorella vulgaris, Chlamydomonas reihardii, Anabaena cylindrica, and Chroococcus turgidus were used to explore the physiological and biochemical effects of glyphosate on algae. Spectrophotometric assays were performed for algal growth, chlorophyll, carotenoids, phycobiliprotein, carbohydrate, and protein. TLC procedures and an image analyzer were used to detect the metabolites of glyphosate inside algal cells. The common visible symptom of glyphosate toxicity in all algal cells were bleaching effect and reduction of contents of carbohydrate, protein, and pigments. The results highly suggested that glyphosate injured the algal cells by destruction of photosynthetic pigments and resulted in lowering the contents of carbohydrate and protein in algal cells.

  4. Aragonite production in calcite seas: effect of seawater Mg/Ca ratio on the calcification and growth of the calcareous algae Penicillus, Halimeda and Udotea

    NASA Astrophysics Data System (ADS)

    Ries, J. B.

    2004-12-01

    Stanley and Hardie (1998, 1999) have shown that secular variation in the Mg/Ca ratio of seawater throughout the Phanerozoic would have subjected the aragonite-producing Codiacean algae to three transitions between the so-called calcite (molar Mg/Ca < 2) and aragonite (molar Mg/Ca > 2) seas, since their origin in the Ordovician (Roux, 1991). They assert that major sediment production by Codiacean algae in recent tropical seas is permitted by the molar Mg/Ca ratio of modern seawater ( ˜5.2) remaining within the range of aragonite seas (molar Mg/Ca > 2). To test this hypothesis, three major sediment producing Codiacean algae, Penicillus capitatus, Halimeda monile and Udotea flabellum, were grown in three artificial ancient seawaters, corresponding to "calcite seas" (molar Mg/Ca = 1.0), "aragonite seas" (molar Mg/Ca = 5.2) and a boundary composition (molar Mg/Ca = 2.5). Significantly, the Penicillus and Udotea specimens maintained their aragonitic mineralogy in each of the artificial seawaters, suggesting either that the algae pump cations to create an internal aragonite nucleation field or employ organic templates specifying the nucleation of the aragonite polymorph (Borowitzka 1984). The Halimeda specimens also produced aragonite in the aragonite and boundary seawaters, but failed to grow at all in the calcite seawater. Linear growth rates, primary productivity and calcification decreased with reductions in ambient Mg/Ca. A stress-strain analysis of the Penicillus thalli revealed that their stiffnesses also decreased with Mg/Ca. The reduced calcification of the algae grown in the calcite and boundary seawaters is probably due to the kinetic difficulty of precipitating aragonite from seawater which does not favor its nucleation. The decreased rates of linear growth and primary production were probably caused by reductions in CO2 available for photosynthesis (CO2 + H2O = CH2O + O2) due to the reduction in calcification (2HCO3 + Ca = CaCO3 + CO2 + H2O). The decrease in

  5. Genotoxic and cytotoxic effects of ZnO nanoparticles for Dunaliella tertiolecta and comparison with SiO2 and TiO2 effects at population growth inhibition levels.

    PubMed

    Schiavo, S; Oliviero, M; Miglietta, M; Rametta, G; Manzo, S

    2016-04-15

    The increasing use of oxide nanoparticles (NPs) in commercial products has intensified the potential release into the aquatic environment where algae represent the basis of the trophic chain. NP effects upon algae population growth were indeed already reported in literature, but the concurrent effects at cellular and genomic levels are still largely unexplored. Our work investigates the genotoxic (by COMET assay) and cytotoxic effects (by qualitative ROS production and cell viability) of ZnO nanoparticles toward marine microalgae Dunaliella tertiolecta. A comparison at defined population growth inhibition levels (i.e. 50% Effect Concentration, EC50, and No Observed Effect Concentration, NOEC) with SiO2 and TiO2 genotoxic effects and previously investigated cytotoxic effects (Manzo et al., 2015) was performed in order to elucidate the possible diverse mechanisms leading to algae growth inhibition. After 72h exposure, ZnO particles act firstly at the level of cell division inhibition (EC50: 2mg Zn/L) while the genotoxic action is evident only starting from 5mg Zn/L. This outcome could be ascribable mainly to the release of toxic ions from the aggregate of ZnO particle in the proximity of cell membrane. In the main, at EC50 and NOEC values for ZnO NPs showed the lowest cytotoxic and genotoxic effect with respect to TiO2 and SiO2. Based on Mutagenic Index (MI) the rank of toxicity is actually: TiO2>SiO2>ZnO with TiO2 and SiO2 that showed similar MI values at both NOEC and EC50 concentrations. The results presented herein suggest that up to TiO2 NOEC (7.5mg/L), the algae DNA repair mechanism is efficient and the DNA damage does not result in an evident algae population growth inhibition. A similar trend for SiO2, although at lower effect level with respect to TiO2, is observable. The comparison among all the tested nanomaterial toxicity patterns highlighted that the algae population growth inhibition occurred through pathways specific for each NP also related to their

  6. Blocking Fibroblast Growth Factor Receptor Signaling Inhibits Tumor Growth, Lymphangiogenesis, and Metastasis

    PubMed Central

    Larrieu-Lahargue, Frédéric; Welm, Alana L.; Bouchecareilh, Marion; Alitalo, Kari; Li, Dean Y.; Bikfalvi, Andreas; Auguste, Patrick

    2012-01-01

    Fibroblast Growth Factor receptor (FGFR) activity plays crucial roles in tumor growth and patient survival. However, FGF (Fibroblast Growth Factor) signaling as a target for cancer therapy has been under-investigated compared to other receptor tyrosine kinases. Here, we studied the effect of FGFR signaling inhibition on tumor growth, metastasis and lymphangiogenesis by expressing a dominant negative FGFR (FGFR-2DN) in an orthotopic mouse mammary 66c14 carcinoma model. We show that FGFR-2DN-expressing 66c14 cells proliferate in vitro slower than controls. 66c14 tumor outgrowth and lung metastatic foci are reduced in mice implanted with FGFR-2DN-expressing cells, which also exhibited better overall survival. We found 66c14 cells in the lumen of tumor lymphatic vessels and in lymph nodes. FGFR-2DN-expressing tumors exhibited a decrease in VEGFR-3 (Vascular Endothelial Growth Factor Receptor-3) or podoplanin-positive lymphatic vessels, an increase in isolated intratumoral lymphatic endothelial cells and a reduction in VEGF-C (Vascular Endothelial Growth Factor-C) mRNA expression. FGFs may act in an autocrine manner as the inhibition of FGFR signaling in tumor cells suppresses VEGF-C expression in a COX-2 (cyclooxygenase-2) or HIF1-α (hypoxia-inducible factor-1 α) independent manner. FGFs may also act in a paracrine manner on tumor lymphatics by inducing expression of pro-lymphangiogenic molecules such as VEGFR-3, integrin α9, prox1 and netrin-1. Finally, in vitro lymphangiogenesis is impeded in the presence of FGFR-2DN 66c14 cells. These data confirm that both FGF and VEGF signaling are necessary for the maintenance of vascular morphogenesis and provide evidence that targeting FGFR signaling may be an interesting approach to inhibit tumor lymphangiogenesis and metastatic spread. PMID:22761819

  7. Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of STAT3 signaling pathway.

    PubMed

    Cai, Qiaoyan; Lin, Jiumao; Wei, Lihui; Zhang, Ling; Wang, Lili; Zhan, Youzhi; Zeng, Jianwei; Xu, Wei; Shen, Aling; Hong, Zhenfeng; Peng, Jun

    2012-01-01

    Signal Transducer and Activator of Transcription 3 (STAT3), a common oncogenic mediator, is constitutively activated in many types of human cancers; therefore it is a major focus in the development of novel anti-cancer agents. Hedyotis diffusa Willd has been used as a major component in several Chinese medicine formulas for the clinical treatment of colorectal cancer (CRC). However, the precise mechanism of its anti-tumor activity remains largely unclear. Using a CRC mouse xenograft model, in the present study we evaluated the effect of the ethanol extract of Hedyotis diffusa Willd (EEHDW) on tumor growth in vivo and investigated the underlying molecular mechanisms. We found that EEHDW reduced tumor volume and tumor weight, but had no effect on body weight gain in CRC mice, demonstrating that EEHDW can inhibit CRC growth in vivo without apparent adverse effect. In addition, EEHDW treatment suppressed STAT3 phosphorylation in tumor tissues, which in turn resulted in the promotion of cancer cell apoptosis and inhibition of proliferation. Moreover, EEHDW treatment altered the expression pattern of several important target genes of the STAT3 signaling pathway, i.e., decreased expression of Cyclin D1, CDK4 and Bcl-2 as well as up-regulated p21 and Bax. These results suggest that suppression of the STAT3 pathway might be one of the mechanisms by which EEHDW treats colorectal cancer. PMID:22754353

  8. HDAC6 inhibition restores ciliary expression and decreases tumor growth

    PubMed Central

    Gradilone, Sergio A; Radtke, Brynn N; Bogert, Pamela S; Huang, Bing Q; Gajdos, Gabriella B; LaRusso, Nicholas F

    2013-01-01

    Primary cilia are multisensory organelles recently found to be absent in some tumor cells, but the mechanisms of deciliation and the role of cilia in tumor biology remain unclear. Cholangiocytes, the epithelial cells lining the biliary tree, normally express primary cilia and their interaction with bile components regulates multiple processes, including proliferation and transport. Utilizing cholangiocarcinoma (CCA) as a model, we found primary cilia are reduced in CCA by a mechanism involving histone deacetylase 6 (HDAC6). The experimental deciliation of normal cholangiocyte cells increased the proliferation rate and induced anchorage-independent growth. Furthermore, deciliation induced the activation of MAPK and Hedgehog signaling, two important pathways involved in CCA development. We found HDAC6 is overexpressed in CCA and overexpression of HDAC6 in normal cholangiocytes induced deciliation, and increased both proliferation and anchorage-independent growth. To evaluate the effect of cilia restoration on tumor cells, we targeted HDAC6 by shRNA or by the pharmacologic inhibitor, tubastatin-A. Both approaches restored the expression of primary cilia in CCA cell lines and decreased cell proliferation and anchorage-independent growth. The effects of tubastatin-A were abolished when CCA cells were rendered unable to regenerate cilia by stable transfection of IFT88-shRNA. Finally, inhibition of HDAC6 by tubastatin-A also induced a significant decrease in tumor growth in a CCA animal model. Our data support a key role for primary cilia in malignant transformation, provide a plausible mechanism for their involvement, and suggest that restoration of primary cilia in tumor cells by HDAC6 targeting may be a potential therapeutic approach for CCA. PMID:23370327

  9. Resveratrol-loaded nanocapsules inhibit murine melanoma tumor growth.

    PubMed

    Carletto, Bruna; Berton, Juliana; Ferreira, Tamara Nascimento; Dalmolin, Luciana Facco; Paludo, Katia Sabrina; Mainardes, Rubiana Mara; Farago, Paulo Vitor; Favero, Giovani Marino

    2016-08-01

    In this study, resveratrol-loaded nanocapsules were developed and its antitumor activity tested on a melanoma mice model. These nanocapsules were spherically-shaped and presented suitable size, negative charge and high encapsulation efficiency for their use as a modified-release system of resveratrol. Nanoencapsulation leads to the drug amorphization. Resveratrol-loaded nanoparticles reduced cell viability of murine melanoma cells. There was a decrease in tumor volume, an increase in the necrotic area and inflammatory infiltrate of melanoma when resveratrol-loaded nanocapsules were compared to free resveratrol in treated mice. Nanoencapsulation of resveratrol also prevented metastasis and pulmonary hemorrhage. This modified-release technology containing resveratrol can be used as a feasible approach in order to inhibit murine melanoma tumor growth. PMID:27070053

  10. Functional Characterization of Pseudomonas Contact Dependent Growth Inhibition (CDI) Systems

    PubMed Central

    Mercy, Chryslène; Ize, Bérengère; Salcedo, Suzana P.; de Bentzmann, Sophie; Bigot, Sarah

    2016-01-01

    Contact-dependent inhibition (CDI) toxins, delivered into the cytoplasm of target bacterial cells, confer to host strain a significant competitive advantage. Upon cell contact, the toxic C-terminal region of surface-exposed CdiA protein (CdiA-CT) inhibits the growth of CDI- bacteria. CDI+ cells express a specific immunity protein, CdiI, which protects from autoinhibition by blocking the activity of cognate CdiA-CT. CdiA-CT are separated from the rest of the protein by conserved peptide motifs falling into two distinct classes, the “E. coli”- and “Burkholderia-type”. CDI systems have been described in numerous species except in Pseudomonadaceae. In this study, we identified functional toxin/immunity genes linked to CDI systems in the Pseudomonas genus, which extend beyond the conventional CDI classes by the variability of the peptide motif that delimits the polymorphic CdiA-CT domain. Using P. aeruginosa PAO1 as a model, we identified the translational repressor RsmA as a negative regulator of CDI systems. Our data further suggest that under conditions of expression, P. aeruginosa CDI systems are implicated in adhesion and biofilm formation and provide an advantage in competition assays. All together our data imply that CDI systems could play an important role in niche adaptation of Pseudomonadaceae. PMID:26808644

  11. Biochemistry of growth inhibition by ammonium ions in mammalian cells

    SciTech Connect

    Ryll, T.; Valley, U.; Wagner, R. . Cell Culture Techniques Dept.)

    1994-06-20

    The intracellular pool of UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine has been shown to act as a central target during the inhibitory action of ammonium ions in vitro cultivated mammalian cell cultures. This pool has been demonstrated to be elevated at the end of a batch cultivation and very quickly as a response to exogenously applied ammonium chloride by using four different cell lines (hybridoma, BHK, CHO, and Ltk-929). The amount of enlarged UDP aminohexoses is correlated to the inhibitor concentration and additionally dependent on the cell line. The formation of the UDP sugars is associated with a transient reduction of the UTP pool. Moreover, the quick formation of UDP-GNAC is strictly dependent on the presence of, glucose and ammonium. Both metabolites act as biochemical precursors. Additionally, the formation of UDP-GNAc after ammonium application has been shown to increase with an elevated cultivation pH and to be independent of the inhibition of transcription and translation processes. The intracellular amount of UDP-GNAc correlates with the level of growth inhibition in mammalian cell lines.

  12. Inhibition of microbial growth on chitosan membranes by plasma treatment.

    PubMed

    de Oliveira Cardoso Macêdo, Marina; de Macêdo, Haroldo Reis Alves; Gomes, Dayanne Lopes; de Freitas Daudt, Natália; Rocha, Hugo Alexandre Oliveira; Alves, Clodomiro

    2013-11-01

    The use of polymeric medical devices has stimulated the development of new sterilization methods. The traditional techniques rely on ethylene oxide, but there are many questions concerning the carcinogenic properties of the ethylene oxide residues adsorbed on the materials after processing. Another common technique is the gamma irradiation process, but it is costly, its safe operation requires an isolated site, and it also affects the bulk properties of the polymers. The use of gas plasma is an elegant alternative sterilization technique. The plasma promotes efficient inactivation of the microorganisms, minimizes damage to the materials, and presents very little danger for personnel and the environment. In this study we used plasma for microbial inhibition of chitosan membranes. The membranes were treated with oxygen, methane, or argon plasma for different time periods (15, 30, 45, or 60 min). For inhibition of microbial growth with oxygen plasma, the time needed was 60 min. For the methane plasma, samples were successfully treated after 30, 45, and 60 min. For argon plasma, all treatment periods were effective. PMID:24251774

  13. Inhibition of growth by erythritol catabolism in Brucella abortus.

    PubMed Central

    Sperry, J F; Robertson, D C

    1975-01-01

    The growth of Brucella abortus (US-19) in a complex tryptose-yeast extract medium containing D-glucose is inhibited by 10 mM erythritol. The enzymes of the erythritol pathway, except for D-erythrulose 1-phosphate dehydrogenase (D-glycero-2-tetrulose 1-phosphate:nicotinamide adenine dinucleotide (NAD+) 4-oxidoreductase) were detected in the soluble and membrane fractions of cell extracts. Glucose catabolism by cell extracts was inhibited by erythritol, whereas, phosphorylated intermediates of the hexose monophosphate pathway were converted to pyruvic acid with oxygen consumption. Erythritol kinase (EC 2.7.1.27; adenosine 5'-triphosphate (ATP): erythritol 1-phosphotransferase) was found to be eightfold higher in activity than the hexokinase in cell extracts. In vivo, ATP is apparently consumed with the accumulation of D-erythrulose 1-phosphate (D-glycero-2-tetrulose 1-phosphate) and no substrate level phosphorylation. ATP levels dropped 10-fold in 30 min after addition of erythritol to log phase cells in tryptose-yeast extract medium with D-glucose as the carbon source. These data suggest bacteriostasis in the presence of erythritol results from the ATP drain caused by erythritol kinase. PMID:170249

  14. Exposure to Asulox Inhibits the Growth of Mosses

    PubMed Central

    ROWNTREE, J. K.; LAWTON, K. F.; RUMSEY, F. J.; SHEFFIELD, E.

    2003-01-01

    Asulox is a herbicide used to control bracken. Its effects on mosses were investigated to ascertain whether exposure proved as detrimental as found in parallel studies on pteridophytes. Mature gametophytes of 18 mosses were exposed to a range of concentrations of Asulox under standard conditions and the effects on growth monitored. Plants were cut to a standard length, exposed to Asulox solution for 24 h, grown for 3 weeks and total elongation (main stem and branches) measured. EC50 values were calculated and species ranked according to sensitivity. The effects of exposure on total elongation were compared with those on main stem elongation alone. Under the conditions tested, the total elongation of all species was inhibited after exposure to Asulox. The amount of elongation observed after exposure was different for different species and inhibition of elongation occurred at different exposure concentrations. A single regression equation was not adequate to describe the dose response curves of all species tested. An ability to produce secondary branches may confer increased tolerance to Asulox exposure. It is concluded that mosses suffer detrimental effects after exposure to Asulox at concentrations similar to those that affect fern gametophytes such as bracken. PMID:12933364

  15. Aurapten, a coumarin with growth inhibition against Leishmania major promastigotes.

    PubMed

    Napolitano, H B; Silva, M; Ellena, J; Rodrigues, B D G; Almeida, A L C; Vieira, P C; Oliva, G; Thiemann, O H

    2004-12-01

    Several natural compounds have been identified for the treatment of leishmaniasis. Among them are some alkaloids, chalcones, lactones, tetralones, and saponins. The new compound reported here, 7-geranyloxycoumarin, called aurapten, belongs to the chemical class of the coumarins and has a molecular weight of 298.37. The compound was extracted from the Rutaceae species Esenbeckia febrifuga and was purified from a hexane extract starting from 407.7 g of dried leaves and followed by four silica gel chromatographic fractionation steps using different solvents as the mobile phase. The resulting compound (47 mg) of shows significant growth inhibition with an LD50 of 30 microM against the tropical parasite Leishmania major, which causes severe clinical manifestations in humans and is endemic in the tropical and subtropical regions. In the present study, we investigated the atomic structure of aurapten in order to determine the existence of common structural motifs that might be related to other coumarins and potentially to other identified inhibitors of Leishmania growth and viability. This compound has a comparable inhibitory activity of other isolated molecules. The aurapten is a planar molecule constituted of an aromatic system with electron delocalization. A hydrophobic side chain consisting of ten carbon atoms with two double bonds and negative density has been identified and may be relevant for further compound synthesis. PMID:15558191

  16. [Mechanism of the inhibitory action of allelochemical dibutyl phthalate on algae Gymnodinium breve].

    PubMed

    Bie, Cong-Cong; Li, Feng-Min; Wang, Yi-Fei; Wang, Hao-Yun; Zhao, Ya-Han; Zhao, Wei; Wang, Zhen-Yu

    2012-01-01

    The aim of this study was to investigate the mechanism of inhibitory action of dibutyl phthalate (DBP) on red tide algae Gymnodinium breve. The effects of DBP on malonaldehyde, subcellular structure and superoxide dismutase (SOD) isoforms were investigated. The results showed that MDA accumulated in the algae cell under DBP exposure, and for the 3 mg x L(-1) DBP treated algae culture a peak value of 0.34 micromol x (10(9) cells) (-1) occurred at 72 h, which was about 2. 3 times than that of the control. TEM pictures showed the disruption of DBP on the subcellular structure of G. breve. A morphological phenomenon appeared that the algae cell was commonly found small tubules or apical parts around the cell membrane, and almost all normal cell organelles were indistinguishable finally. The activity of CuZn-SOD (main cytoplast located isoform with little in cloroplast) under DBP exposure was higher than that of the control, and no significant difference was observed on Fe-SOD (chloroplast located isoform) activity, but for the Mn-SOD (mitochondrial isoform), the activity was significantly inhibited. These results indicated that DBP might inhibit the algae growth from the plasma membrane and the mitochondria, resulting in oxidative damage in algae cell and a final death. This paper will give a theoretical support to the practical usage of the allelochemical on red tide algae. PMID:22452215

  17. Do furanic and phenolic compounds of lignocellulosic and algae biomass hydrolyzate inhibit anaerobic mixed cultures? A comprehensive review.

    PubMed

    Monlau, F; Sambusiti, C; Barakat, A; Quéméneur, M; Trably, E; Steyer, J-P; Carrère, H

    2014-01-01

    Nowadays there is a growing interest on the use of both lignocellulosic and algae biomass to produce biofuels (i.e. biohydrogen, ethanol and methane), as future alternatives to fossil fuels. In this purpose, thermal and thermo-chemical pretreatments have been widely investigated to overcome the natural physico-chemical barriers of such biomass and to enhance biofuel production from lignocellulosic residues and, more recently, marine biomass (i.e. macro and microalgae). However, the pretreatment technologies lead not only to the conversion of carbohydrate polymers (ie cellulose, hemicelluloses, starch, agar) to soluble monomeric sugar (ie glucose, xylose, arabinose, galactose), but also the generation of various by-products (i.e. furfural and 5-HMF). In the case of lignocellulosic residues, part of the lignin can also be degraded in lignin derived by-products, mainly composed of phenolic compounds. Although the negative impact of such by-products on ethanol production has been widely described in literature, studies on their impact on biohydrogen and methane production operated with mixed cultures are still very limited. This review aims to summarise and discuss literature data on the impact of pre-treatment by-products on H2-producing dark fermentation and anaerobic digestion processes when using mixed cultures as inoculum. As a summary, furanic (5-HMF, furfural) and phenolic compounds were found to be stronger inhibitors of the microbial dark fermentation than the full anaerobic digestion process. Such observations can be explained by differences in process parameters: anaerobic digestion is performed with more complex mixed cultures, lower substrate/inoculum and by-products/inoculum ratios and longer batch incubation times than dark fermentation. Finally, it has been reported that, during dark fermentation process, the presence of by-products could lead to a metabolic shift from H2-producing pathways (i.e. acetate and butyrate) to non-H2-producing pathways (i

  18. Combined MET inhibition and topoisomerase I inhibition block cell growth of small cell lung cancer.

    PubMed

    Rolle, Cleo E; Kanteti, Rajani; Surati, Mosmi; Nandi, Suvobroto; Dhanasingh, Immanuel; Yala, Soheil; Tretiakova, Maria; Arif, Qudsia; Hembrough, Todd; Brand, Toni M; Wheeler, Deric L; Husain, Aliya N; Vokes, Everett E; Bharti, Ajit; Salgia, Ravi

    2014-03-01

    Small cell lung cancer (SCLC) is a devastating disease, and current therapies have not greatly improved the 5-year survival rates. Topoisomerase (Top) inhibition is a treatment modality for SCLC; however, the response is short lived. Consequently, our research has focused on improving SCLC therapeutics through the identification of novel targets. Previously, we identified MNNG HOS transforming gene (MET) to be overexpressed and functional in SCLC. Herein, we investigated the therapeutic potential of combinatorial targeting of MET using SU11274 and Top1 using 7-ethyl-10-hydroxycamptothecin (SN-38). MET and TOP1 gene copy numbers and protein expression were determined in 29 patients with limited (n = 11) and extensive (n = 18) disease. MET gene copy number was significantly increased (>6 copies) in extensive disease compared with limited disease (P = 0.015). Similar TOP1 gene copy numbers were detected in limited and extensive disease. Immunohistochemical staining revealed a significantly higher Top1 nuclear expression in extensive (0.93) versus limited (0.15) disease (P = 0.04). Interestingly, a significant positive correlation was detected between MET gene copy number and Top1 nuclear expression (r = 0.5). In vitro stimulation of H82 cells revealed hepatocyte growth factor (HGF)-induced nuclear colocalization of p-MET and Top1. Furthermore, activation of the HGF/MET axis enhanced Top1 activity, which was abrogated by SU11274. Combination of SN-38 with SU11274 dramatically decreased SCLC growth as compared with either drug alone. Collectively, these findings suggest that the combinatorial inhibition of MET and Top1 is a potentially efficacious treatment strategy for SCLC. PMID:24327519

  19. Antibiotic activity of lectins from marine algae against marine vibrios.

    PubMed

    Liao, W-R; Lin, J-Y; Shieh, W-Y; Jeng, W-L; Huang, R

    2003-07-01

    Saline and aqueous ethanol extracts of marine algae and the lectins from two red algal species were assayed for their antibiotic activity against marine vibrios. Experimental studies were also carried out on the influence of environmental factors on such activity, using batch cultures. The results indicated that many of the saline extracts of the algal species were active and that the activity was selective against those vibrios assayed. The algal extracts were active against Vibrio pelagius and the fish pathogen V. vulnificus, but inactive against V. neresis. Algal lectins from Eucheuma serra (ESA) and Galaxaura marginata (GMA) strongly inhibited V. vulnificus but were inactive against the other two vibrios. The antibacterial activity of algal extracts was inhibited by pretreatment with various sugars and glycoprotein. Extracts of the two red algae, E. serra and Pterocladia capillacea, in saline and aqueous ethanol, inhibited markedly the growth rate of V. vulnificus at very low concentrations. Culture results indicated that metabolites active against V. vulnificus were invariably produced in P. capillacea over a wide range of temperature, light intensity, and nutritional conditions. Enhanced antibacterial activity occurred when P. capillacea was grown under higher irradiance, severe nutrient stress and moderate temperature (20 degrees C), reflecting the specific antibiotic characteristics of this alga. The strong antibiotic activity of lectins towards fish pathogenic bacteria reveals one of the important roles played by algal lectins, as well as the potential high economic value of those marine algae assayed for aquaculture and for biomedical purposes. PMID:12884128

  20. Epidermal growth factor receptor inhibition in metastatic anal cancer.

    PubMed

    Rogers, Jane E; Ohinata, Aki; Silva, Ninoska N; Mehdizadeh, Amir; Eng, Cathy

    2016-09-01

    Metastatic squamous cell carcinoma (SCCA) anal cancer is relatively rare. With limited data, cisplatin plus 5-fluorouracil has traditionally been utilized in the first-line setting. Treatment beyond front-line cisplatin progression is not well defined. Epidermal growth factor receptor (EGFR) is highly overexpressed in SCCA anal cancer and EGFR inhibition may represent a potential treatment target for this population in need. Our case series evaluated metastatic SCCA anal cancer patients who received an EGFR monoclonal antibody as second-line or third-line therapy. Data collected consisted of demographics, previous treatment, metastatic disease sites, localized therapy received, regimen received, first radiographic result, progression-free survival, and overall survival. A total of 17 patients were included, with most (76%) patients receiving an EGFR monoclonal antibody in the second-line setting. Common regimens identified combined cetuximab or panitumumab with a fluoropyrimidine plus platinum (35%), carboplatin plus paclitaxel (29%), or cisplatin plus vinorelbine (18%). Thirty-five percent of patients achieved a response and 24% had stable disease. The overall median progression-free survival and overall survival were 7.3 and 24.7 months, respectively. Compared with our large retrospective study in the front-line metastatic anal cancer setting, our study suggests that anti-EGFR therapy in combination with certain chemotherapy derived additional benefit in the refractory setting. In the metastatic setting, there is a need to discover effective therapies. We present a diverse metastatic SCCA anal cancer patient population who received cetuximab or panitumumab with chemotherapy in the second-line or third-line setting. Our case series strengthens the concept of EGFR inhibition in metastatic SCCA anal cancer. PMID:27272412

  1. Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation.

    PubMed

    Bennett, Darin C; Leung, Gigi; Wang, Eddy; Ma, Sam; Lo, Blanche K K; McElwee, Kevin J; Cheng, Kimberly M

    2015-09-01

    Traditionally, native Australian aborigines have used emu oil for the treatment of inflammation and to accelerate wound healing. Studies on mice suggest that topically applied emu oil may have anti-inflammatory properties and may promote wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1 rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea tree, and olive oils were used as comparative controls. The same oils at 0.5% concentration were evaluated for their influence on peripheral blood mononuclear cell (PBMC) survival over 48 hr and their ability to inhibit IFNγ production in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no oil control, significantly shorter population doubling time durations were observed for HaCaT cells cultured in emu oil (1.51×faster), ostrich oil (1.46×faster), and rhea oil (1.64×faster). Tea tree oil demonstrated significant antiproliferative activity and olive oil significantly prolonged (1.35×slower) cell population doubling time. In contrast, almost all oils, particularly tea tree oil, significantly reduced PBMC viability. Different oils had different levels of inhibitory effect on IFNγ production with individual emu, ostrich, rhea, and duck oil samples conferring full inhibition. This preliminary investigation suggests that emu oil might promote wound healing by accelerating the growth rate of keratinocytes. Combined with anti-inflammatory properties, ratite oil may serve as a useful component in bandages and ointments for the treatment of wounds and inflammatory skin conditions. PMID:26217022

  2. Ratite oils promote keratinocyte cell growth and inhibit leukocyte activation

    PubMed Central

    Bennett, Darin C.; Leung, Gigi; Wang, Eddy; Ma, Sam; Lo, Blanche K. K.; McElwee, Kevin J.; Cheng, Kimberly M.

    2015-01-01

    Traditionally, native Australian aborigines have used emu oil for the treatment of inflammation and to accelerate wound healing. Studies on mice suggest that topically applied emu oil may have anti-inflammatory properties and may promote wound healing. We investigated the effects of ratite oils (6 emu, 3 ostrich, 1 rhea) on immortalized human keratinocytes (HaCaT cells) in vitro by culturing the cells in media with oil concentrations of 0%, 0.5%, and 1.0%. Peking duck, tea tree, and olive oils were used as comparative controls. The same oils at 0.5% concentration were evaluated for their influence on peripheral blood mononuclear cell (PBMC) survival over 48 hr and their ability to inhibit IFNγ production in PBMCs activated by phytohemagglutinin (PHA) in ELISpot assays. Compared to no oil control, significantly shorter population doubling time durations were observed for HaCaT cells cultured in emu oil (1.51 × faster), ostrich oil (1.46 × faster), and rhea oil (1.64 × faster). Tea tree oil demonstrated significant antiproliferative activity and olive oil significantly prolonged (1.35 × slower) cell population doubling time. In contrast, almost all oils, particularly tea tree oil, significantly reduced PBMC viability. Different oils had different levels of inhibitory effect on IFNγ production with individual emu, ostrich, rhea, and duck oil samples conferring full inhibition. This preliminary investigation suggests that emu oil might promote wound healing by accelerating the growth rate of keratinocytes. Combined with anti-inflammatory properties, ratite oil may serve as a useful component in bandages and ointments for the treatment of wounds and inflammatory skin conditions. PMID:26217022

  3. Dll4 Inhibition plus Aflibercept Markedly Reduces Ovarian Tumor Growth.

    PubMed

    Huang, Jie; Hu, Wei; Hu, Limin; Previs, Rebecca A; Dalton, Heather J; Yang, Xiao-Yun; Sun, Yunjie; McGuire, Michael; Rupaimoole, Rajesha; Nagaraja, Archana S; Kang, Yu; Liu, Tao; Nick, Alpa M; Jennings, Nicholas B; Coleman, Robert L; Jaffe, Robert B; Sood, Anil K

    2016-06-01

    Delta-like ligand 4 (Dll4), one of the Notch ligands, is overexpressed in ovarian cancer, especially in tumors resistant to anti-VEGF therapy. Here, we examined the biologic effects of dual anti-Dll4 and anti-VEGF therapy in ovarian cancer models. Using Dll4-Fc blockade and anti-Dll4 antibodies (murine REGN1035 and human REGN421), we evaluated the biologic effects of Dll4 inhibition combined with aflibercept or chemotherapy in orthotopic mouse models of ovarian cancer. We also examined potential mechanisms by which dual Dll4 and VEGF targeting inhibit tumor growth using immunohistochemical staining for apoptosis and proliferation markers. Reverse-phase protein arrays were used to identify potential downstream targets of Dll4 blockade. Dual targeting of VEGF and Dll4 with murine REGN1035 showed superior antitumor effects in ovarian cancer models compared with either monotherapy. In the A2780 model, REGN1035 (targets murine Dll4) or REGN421 (targets human Dll4) reduced tumor weights by 62% and 82%, respectively; aflibercept alone reduced tumor weights by 90%. Greater therapeutic effects were observed for Dll4 blockade (REGN1035) combined with either aflibercept or docetaxel (P < 0.05 for the combination vs. aflibercept). The superior antitumor effects of REGN1035 and aflibercept were related to increased apoptosis in tumor cells compared with the monotherapy. We also found that GATA3 expression was significantly increased in tumor stroma from the mice treated with REGN1035 combined with docetaxel or aflibercept, suggesting an indirect effect of these combination treatments on the tumor stroma. These findings identify that dual targeting of Dll4 and VEGF is an attractive therapeutic approach. Mol Cancer Ther; 15(6); 1344-52. ©2016 AACR. PMID:27009216

  4. Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects.

    PubMed

    Wang, Shuaiyu; Wang, Li-Jun; Jiang, Bo; Wu, Ning; Li, Xiangqian; Liu, Shaofang; Luo, Jiao; Shi, Dayong

    2015-01-01

    Bis-(2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a bromophenol first isolated from Rhodomelaceae confervoides. Our previous studies showed that BDDPM exerts PTP1B-inhibiting activity and anti-cancer activity against a wide range of tumor cells while it also showed lower cytotoxicity against normal cells. In the present study, we found that BDDPM exhibits significant activities toward angiogenesis in vitro. BDDPM inhibits multiple angiogenesis processes, including endothelial cell sprouting, migration, proliferation, and tube formation. Further kinase assays investigations found that BDDPM is a potent selective, but multi-target, receptor tyrosine kinase (RTKs) inhibitor. BDDPM (10 μM) inhibits the activities of fibroblast growth factor receptor 2 and 3 (FGFR2, 3), vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptor α (PDGFRα) (inhibition rate: 57.7%, 78.6%, 78.5% and 71.1%, respectively). Moreover, BDDPM also decreases the phosphorylation of protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS), as well as nitric oxide (NO) production in a dose dependent manner. These results indicate that BDDPM can be exploited as an anti-angiogenic drug, or as a lead compound for the development of novel multi-target RTKs inhibitors. PMID:26075871

  5. Anti-Angiogenic Properties of BDDPM, a Bromophenol from Marine Red Alga Rhodomela confervoides, with Multi Receptor Tyrosine Kinase Inhibition Effects

    PubMed Central

    Wang, Shuaiyu; Wang, Li-Jun; Jiang, Bo; Wu, Ning; Li, Xiangqian; Liu, Shaofang; Luo, Jiao; Shi, Dayong

    2015-01-01

    Bis-(2,3-dibromo-4,5-dihydroxy-phenyl)-methane (BDDPM) is a bromophenol first isolated from Rhodomelaceae confervoides. Our previous studies showed that BDDPM exerts PTP1B-inhibiting activity and anti-cancer activity against a wide range of tumor cells while it also showed lower cytotoxicity against normal cells. In the present study, we found that BDDPM exhibits significant activities toward angiogenesis in vitro. BDDPM inhibits multiple angiogenesis processes, including endothelial cell sprouting, migration, proliferation, and tube formation. Further kinase assays investigations found that BDDPM is a potent selective, but multi-target, receptor tyrosine kinase (RTKs) inhibitor. BDDPM (10 μM) inhibits the activities of fibroblast growth factor receptor 2 and 3 (FGFR2, 3), vascular endothelial growth factor receptor 2 (VEGFR2) and platelet-derived growth factor receptor α (PDGFRα) (inhibition rate: 57.7%, 78.6%, 78.5% and 71.1%, respectively). Moreover, BDDPM also decreases the phosphorylation of protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS), as well as nitric oxide (NO) production in a dose dependent manner. These results indicate that BDDPM can be exploited as an anti-angiogenic drug, or as a lead compound for the development of novel multi-target RTKs inhibitors. PMID:26075871

  6. MECHANISMS OF FLUID SHEAR-INDUCED INHIBITION OF POPULATION GROWTH IN A RED-TIDE DINOFLAGELLATE

    EPA Science Inventory

    Net population growth of some dinoflagellates is inhibited by fluid shear at shear stresses comparable with those generated during oceanic turbulence. Decreased net growth may occur through lowered cell division, increased mortality, or both. The dominant mechanism under various ...

  7. Cellular Auxin Transport in Algae

    PubMed Central

    Zhang, Suyun; van Duijn, Bert

    2014-01-01

    The phytohormone auxin is one of the main directors of plant growth and development. In higher plants, auxin is generated in apical plant parts and transported from cell-to-cell in a polar fashion. Auxin is present in all plant phyla, and the existence of polar auxin transport (PAT) is well established in land plants. Algae are a group of relatively simple, autotrophic, photosynthetic organisms that share many features with land plants. In particular, Charophyceae (a taxon of green algae) are closest ancestors of land plants. In the study of auxin function, transport and its evolution, the algae form an interesting research target. Recently, proof for polar auxin transport in Chara species was published and auxin related research in algae gained more attention. In this review we discuss auxin transport in algae with respect to land plants and suggest directions for future studies. PMID:27135491

  8. Cellular Auxin Transport in Algae.

    PubMed

    Zhang, Suyun; van Duijn, Bert

    2014-01-01

    The phytohormone auxin is one of the main directors of plant growth and development. In higher plants, auxin is generated in apical plant parts and transported from cell-to-cell in a polar fashion. Auxin is present in all plant phyla, and the existence of polar auxin transport (PAT) is well established in land plants. Algae are a group of relatively simple, autotrophic, photosynthetic organisms that share many features with land plants. In particular, Charophyceae (a taxon of green algae) are closest ancestors of land plants. In the study of auxin function, transport and its evolution, the algae form an interesting research target. Recently, proof for polar auxin transport in Chara species was published and auxin related research in algae gained more attention. In this review we discuss auxin transport in algae with respect to land plants and suggest directions for future studies. PMID:27135491

  9. An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth.

    PubMed

    Chen, Yan; Liu, Xin; Jin, Cong Guo; Zhou, Yong Chun; Navab, Roya; Jakobsen, Kristine Raaby; Chen, Xiao Qun; Li, Jia; Li, Ting Ting; Luo, Lu; Wang, Xi Cai

    2016-02-01

    Lung cancer is the leading cause of mortality and 5-year survival rate is very low worldwide. Recent studies show that vascular endothelial growth factor receptor-3 (VEGFR-3) signaling pathway contributes to lung cancer progression. So we hypothesize that an oral DNA vaccine that targets VEGFR-3 carried by attenuated Salmonella enterica serovar typhimurium strain SL3261 has impacts on lung cancer progression. In this study, the oral VEGFR-3-based vaccine-immunized mice showed appreciable inhibition of tumor growth and tumor lymphatic microvessels in lung cancer mice model. Moreover, the oral VEGFR-3-based vaccine-immunized mice showed remarkable increases in both VEGFR-3-specific antibody levels and cytotoxic activity. Furthermore, the oral VEGFR-3-based vaccine-immunized mice showed a significant increase in the levels of T helper type 1 (Th1) cell intracellular cytokine expression (IL-2, IFN-γ, and TNF-α). After inoculation with murine Lewis lung carcinoma (LLC) cells, CD4(+) or CD8(+) T cell numbers obviously declined in control groups whereas high levels were maintained in the oral VEGFR-3-based vaccine group. These results demonstrated that the oral VEGFR-3-based vaccine could induce specific humoral and cellular immune responses and then significantly inhibit lung carcinoma growth via suppressing lymphangiogenesis. PMID:26376999

  10. Inhibition of mitogen stimulated growth of human colon cancer cells by interferon.

    PubMed Central

    Hamburger, A. W.; Condon, M. E.; O'Donnell, K.

    1988-01-01

    Recombinant human interferon alpha inhibits growth of a human colon cancer cell line, Colo 205. To explore the mechanisms of IFN induced growth inhibition, quiescent Colo 205 cells were stimulated to proliferate in serum-free media by defined growth factors. Addition of insulin, transferrin and selenium (ITS) stimulated DNA synthesis, as measured by 3H-thymidine incorporation, in a dose-dependent manner. IFN-alpha (at concentrations greater than 100 U ml-1) inhibited ITS stimulated DNA synthesis by 63%. Inhibition of cell cycle traverse was confirmed by flow cytometric analysis. Although IFN inhibited growth of ITS-treated cells, steady state levels of c-myc mRNA remained above levels observed in unstimulated cells. IFN inhibited DNA synthesis only when added prior to mitogen stimulation. IFN, added 6 h after exposure of quiescent cells to ITS, failed to inhibit cell growth. Addition of increasing concentrations of ITS failed to overcome the IFN-induced growth inhibition. These results suggest IFN may inhibit cell growth in part by antagonizing the action of growth factors. Images Figure 4 PMID:3166905

  11. Endothelin inhibits cholangiocarcinoma growth by a decrease in the vascular endothelial growth factor expression

    PubMed Central

    Fava, Giammarco; DeMorrow, Sharon; Gaudio, Eugenio; Franchitto, Antonio; Onori, Paolo; Carpino, Guido; Glaser, Shannon; Francis, Heather; Coufal, Monique; Marucci, Luca; Alvaro, Domenico; Marzioni, Marco; Horst, Trenton; Mancinelli, Romina; Benedetti, Antonio; Alpini, Gianfranco

    2009-01-01

    Background: Endothelins (ET-1, ET-2, ET-3) are peptides with vasoactive properties interacting with ETA and ETB receptors. ET-1 inhibits secretin-stimulated ductal secretion (hallmark of cholangiocyte growth) of cholestatic rats by interaction with ET receptors. Aim: The aims of the studies were to evaluate (i) the effect of ET-1 on cholangiocarcinoma growth in Mz-ChA-1 cells and nude mice and (ii) whether ET-1 regulation of cholangiocarcinoma growth is associated with changes in the expression of vascular endothelial growth factor-A (VEGF-A), VEGF-C, VEGF receptor-2 (VEGFR-2) and VEGFR-3. Methods: We determined the expression of ETA and ETB receptors on normal and malignant (Mz-ChA-1) cholangiocytes and human cholangiocarcinoma tissue and the effect of ET-1 on the proliferation and expression of VEGF-A, VEGF-C (regulators of tumour angiogenesis) and its receptors, VEGFR-2 and VEGFR-3, in Mz-ChA-1 cells. In vivo, Mz-ChA-1 cells were injected into the flanks of athymic mice and injections of ET-1 or saline into the tumours were performed daily. The effect of ET-1 on tumour size, cell proliferation, apoptosis, collagen quantity and the expression of VEGF-A and VEGF-C and VEGFR-2 and VEGFR-3 were measured after 73 days. Results: Higher expression of ETA and ETB was observed in malignant compared with normal cholangiocytes. ET-1 inhibited proliferation and VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression of Mz-ChA-1 cells. Chronic ET-1 treatment decreased tumour volume, tumour cell proliferation and VEGF-A and VEGF-C expression but increased apoptosis and collagen tissue deposition compared with controls. Conclusions: Modulation of VEGF-A and VEGF-C (by ET-1) may be important for managing cholangiocarcinoma growth. PMID:19291182

  12. Targeting Insulin-Like Growth Factor 1 Receptor Inhibits Pancreatic Cancer Growth and Metastasis

    PubMed Central

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Arumugam, Arunkumar; Nandy, Sushmita; Boopalan, Thiyagarajan; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is one of the most lethal cancers. Increasing incidence and mortality indicates that there is still much lacking in detection and management of the disease. This is partly due to a lack of specific symptoms during early stages of the disease. Several growth factor receptors have been associated with pancreatic cancer. Here, we have investigated if an RNA interference approach targeted to IGF-IR could be effective and efficient against pancreatic cancer growth and metastasis. For that, we evaluated the effects of IGF-1R inhibition using small interfering RNA (siRNAs) on tumor growth and metastasis in HPAC and PANC-1 pancreatic cancer cell lines. We found that silencing IGF-1R inhibits pancreatic cancer growth and metastasis by blocking key signaling pathways such AKT/PI3K, MAPK, JAK/STAT and EMT. Silencing IGF-1R resulted in an anti-proliferative effect in PANC-1 and HPAC pancreatic cancer cell lines. Matrigel invasion, transwell migration and wound healing assays also revealed a role for IGF-1R in metastatic properties of pancreatic cancer. These results were further confirmed using Western blotting analysis of key intermediates involved in proliferation, epithelial mesenchymal transition, migration, and invasion. In addition, soft agar assays showed that silencing IGF-1R also blocks the colony forming capabilities of pancreatic cancer cells in vitro. Western blots, as well as, flow cytometric analysis revealed the induction of apoptosis in IGF-1R silenced cells. Interestingly, silencing IGF-1R also suppressed the expression of insulin receptor β. All these effects together significantly control pancreatic cancer cell growth and metastasis. To conclude, our results demonstrate the significance of IGF-1R in pancreatic cancer. PMID:24809702

  13. Growth of Steptomyces hygroscopicus in rotating-wall bioreactor under simulated microgravity inhibits rapamycin production

    NASA Technical Reports Server (NTRS)

    Fang, A.; Pierson, D. L.; Mishra, S. K.; Demain, A. L.

    2000-01-01

    Growth of Streptomyces hygroscopicus under conditions of simulated microgravity in a rotating-wall bioreactor resulted in a pellet form of growth, lowered dry cell weight, and inhibition of rapamycin production. With the addition of Teflon beads to the bioreactor, growth became much less pelleted, dry cell weight increased but rapamycin production was still markedly inhibited. Growth under simulated microgravity favored extracellular production of rapamycin, in contrast to a greater percentage of cell-bound rapamycin observed under normal gravity conditions.

  14. Growth of Streptomyces Hygroscopicus in Rotating-Wall Bioreactor Under Simulated Microgravity Inhibits Rapamycin Production

    NASA Technical Reports Server (NTRS)

    Fang, A.; Pierson, D. L.; Mishra, S. K.; Demain, A. L.

    2000-01-01

    Growth of Streptomyces hygroscopicus under conditions of simulated microgravity in a rotating-wall bioreactor resulted in a pellet form of growth, lowered dry cell weight, and inhibition of rapamycin production. With the addition of Teflon beads to the bioreactor, growth became much less pelleted, dry cell weight increased but rapamycin production was still markedly inhibited. Growth under simulated microgravity favored extracellular production of rapamycin in contrast to a greater percentage of cell-bound rapamycin observed under normal gravity conditions.

  15. Edible blue-green algae reduce the production of pro-inflammatory cytokines by inhibiting NF-κB pathway in macrophages and splenocytes

    PubMed Central

    Ku, Chai Siah; Pham, Tho X.; Park, Youngki; Kim, Bohkyung; Shin, Min; Kang, Insoo; Lee, Jiyoung

    2013-01-01

    Background Chronic inflammation contributes to the development of pathological disorders including insulin resistance and atherosclerosis. Identification of anti-inflammatory natural products can prevent the inflammatory diseases. Methods Anti-inflammatory effects of blue-green algae (BGA), i.e., Nostoc commune var. Sphaeroides Kützing (NO) and Spirulina Platensis (SP), were compared in RAW 264.7 and mouse bone marrow-derived macrophages (BMM) as well as splenocytes from apolipoprotein E knockout (apoE−/−) mice fed BGA. Results When macrophages pretreated with 100 μg/ml NO lipid extract (NOE) or SP lipid extract (SPE) were activated by lipopolysaccharide (LPS), expression and secretion of pro-inflammatory cytokines, such as tumor necrosis factor α (TNFα), interleukin 1β (IL-1β), and IL-6, were significantly repressed. NOE and SPE also significantly repressed the expression of TNFα and IL-1β in BMM. LPS-induced secretion of IL-6 was lower in splenocytes from apoE−/− fed an atherogenic diet containing 5% NO or SP for 12 weeks. In RAW 264.7 macrophages, NOE and SPE markedly decreased nuclear translocation of NF-κB. The degree of repression of pro-inflammatory gene expression by algal extracts was much stronger than that of SN50, an inhibitor of NF-κB nuclear translocation. Trichostatin A, a pan histone deacetylase inhibitor, increased basal expression of IL-1β and attenuated the repression of the gene expression by SPE. SPE significantly down-regulated mRNA abundance of 11 HDAC isoforms, consequently increasing acetylated histone 3 levels. Conclusion NOE and SPE repress pro-inflammatory cytokine expression and secretion in macrophages and splenocytes via inhibition of NF-κB pathway. Histone acetylation state is likely involved in the inhibition. General significance This study underscores natural products can exert anti-inflammatory effects by epigenetic modifications such as histone acetylation. PMID:23357040

  16. Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth

    PubMed Central

    Sano, Michael B.; Arena, Christopher B.; Bittleman, Katelyn R.; DeWitt, Matthew R.; Cho, Hyung J.; Szot, Christopher S.; Saur, Dieter; Cissell, James M.; Robertson, John; Lee, Yong W.; Davalos, Rafael V.

    2015-01-01

    Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models. PMID:26459930

  17. Further evidence that naphthoquinone inhibits Toxoplasma gondii growth in vitro.

    PubMed

    da Silva, Luciana Lemos Rangel; Portes, Juliana de Araujo; de Araújo, Marlon Heggdorne; Silva, Jéssica Lays Sant'ana; Rennó, Magdalena Nascimento; Netto, Chaquip Daher; da Silva, Alcides José Monteiro; Costa, Paulo Roberto Ribeiro; De Souza, Wanderley; Seabra, Sergio Henrique; DaMatta, Renato Augusto

    2015-12-01

    Toxoplasmosis is a widely disseminated disease caused by Toxoplasma gondii, an intracellular protozoan parasite. Standard treatment causes many side effects, such as depletion of bone marrow cells, skin rashes and gastrointestinal implications. Therefore, it is necessary to find chemotherapeutic alternatives for the treatment of this disease. It was shown that a naphthoquinone derivative compound is active against T. gondii, RH strain, with an IC50 around 2.5 μM. Here, three different naphthoquinone derivative compounds with activity against leukemia cells and breast carcinoma cell were tested against T. gondii (RH strain) infected LLC-MK2 cell line. All the compounds were able to inhibit parasite growth in vitro, but one of them showed an IC50 activity below 1 μM after 48 h of treatment. The compounds showed low toxicity to the host cell. In addition, these compounds were able to induce tachyzoite-bradyzoite conversion confirmed by morphological changes, Dolichus biflorus lectin cyst wall labeling and characterization of amylopectin granules in the parasites by electron microscopy analysis using the Thierry technique. Furthermore, the compounds induced alterations on the ultrastructure of the parasite. Taken together, our results point to the naphthoquinone derivative (LQB 151) as a potential compound for the development of new drugs for the treatment of toxoplasmosis. PMID:26335616

  18. Growth Hormone Inhibits Hepatic De Novo Lipogenesis in Adult Mice.

    PubMed

    Cordoba-Chacon, Jose; Majumdar, Neena; List, Edward O; Diaz-Ruiz, Alberto; Frank, Stuart J; Manzano, Anna; Bartrons, Ramon; Puchowicz, Michelle; Kopchick, John J; Kineman, Rhonda D

    2015-09-01

    Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. GH replacement can resolve the fatty liver condition in diet-induced obese rodents and in GH-deficient patients. However, it remains to be determined whether this inhibitory action of GH is due to direct regulation of hepatic lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, GH receptor (GHR) knockdown (aLivGHRkd) mouse was developed to model hepatic GH resistance in humans that may occur after sexual maturation. Just 7 days after aLivGHRkd, hepatic de novo lipogenesis (DNL) was increased in male and female chow-fed mice, compared with GHR-intact littermate controls. However, hepatosteatosis developed only in male and ovariectomized female aLivGHRkd mice. The increase in DNL observed in aLivGHRkd mice was not associated with hyperactivation of the pathway by which insulin is classically considered to regulate DNL. However, glucokinase mRNA and protein levels as well as fructose-2,6-bisphosphate levels were increased in aLivGHRkd mice, suggesting that enhanced glycolysis drives DNL in the GH-resistant liver. These results demonstrate that hepatic GH actions normally serve to inhibit DNL, where loss of this inhibitory signal may explain, in part, the inappropriate increase in hepatic DNL observed in NAFLD patients. PMID:26015548

  19. Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth

    NASA Astrophysics Data System (ADS)

    Sano, Michael B.; Arena, Christopher B.; Bittleman, Katelyn R.; Dewitt, Matthew R.; Cho, Hyung J.; Szot, Christopher S.; Saur, Dieter; Cissell, James M.; Robertson, John; Lee, Yong W.; Davalos, Rafael V.

    2015-10-01

    Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models.

  20. Chinese medicinal herbs inhibit growth of murine renal cell carcinoma.

    PubMed

    Lau, B H; Ruckle, H C; Botolazzo, T; Lui, P D

    1994-01-01

    Tumors are known to produce factors suppressing immune functions. We previously showed that a murine renal cell carcinoma (Renca) suppressed macrophage function in vitro and that this suppression was abolished by co-incubation with extracts of two Chinese medicinal herbs. We now report that these phytochemicals are capable of inhibiting growth of Renca in vivo. BALB/c mice were transplanted intraperitoneally (IP) with 1-2 x 10(5) Renca cells. One day after tumor transplant, mice were randomized into two groups. One group was treated IP, daily for 10 days, with 100 microliters of phytochemicals containing 500 micrograms each of Astragalus membranaceus and Ligustrum lucidum, while the other group received saline as controls. A cure rate of 57% was obtained with these phytochemicals when the initial tumor load was 2 x 10(5), and 100% when the initial tumor load was 1 x 10(5). Additional experiments were performed to investigate the mechanisms involved in this protection. Splenic macrophages from tumor-bearing mice were shown to have depressed chemiluminescent oxidative burst activity, and this depression was restored with phytochemical treatment. Splenocytes from mice transplanted with Renca responded less favorably to interleukin-2 (IL-2) in generating lymphokine-activated killer (LAK) cells; again this depression was restored with phytochemical treatment. Our data suggest that these phytochemicals may have exerted their antitumor effects via augmentation of phagocyte and LAK cell activities. PMID:7812364

  1. Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth.

    PubMed

    Sano, Michael B; Arena, Christopher B; Bittleman, Katelyn R; DeWitt, Matthew R; Cho, Hyung J; Szot, Christopher S; Saur, Dieter; Cissell, James M; Robertson, John; Lee, Yong W; Davalos, Rafael V

    2015-01-01

    Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models. PMID:26459930

  2. MiR-503 inhibits hepatocellular carcinoma cell growth via inhibition of insulin-like growth factor 1 receptor

    PubMed Central

    Xiao, Yao; Tian, Qinggang; He, Jiantai; Huang, Ming; Yang, Chao; Gong, Liansheng

    2016-01-01

    MicroRNAs (miRs) have been demonstrated to play key roles in the development and progression of hepatocellular carcinoma (HCC). However, the regulatory mechanism of miR-503 in HCC has not been fully uncovered. In this study, we found that miR-503 was significantly downregulated in HCC tissues compared to nontumorous liver tissues. Moreover, lower miR-503 levels were associated with the malignant progression of HCC, and the expression of miR-503 was also decreased in several common HCC cell lines compared to normal human liver cell line THLE-3. Overexpression of miR-503 inhibited proliferation but induced apoptosis of LM3 and HepG2 cells. Bioinformatical analysis and luciferase reporter assay further identified insulin-like growth factor 1 receptor (IGF-1R) as a novel target of miR-503 in 293T cells. Moreover, overexpression of miR-503 led to a significant decrease in the protein levels of IGF-1R, while knockdown of miR-503 enhanced its protein levels in LM3 and HepG2 cells. Besides, overexpression of IGF-1R reversed the effects of miR-503-mediated HCC cell proliferation and apoptosis, indicating that IGF-1R acts as a downstream effector of miR-503 in HCC cells. Furthermore, IGF-1R was found to be significantly upregulated in HCC tissues compared to nontumorous liver tissues. In addition, the mRNA levels of IGF-1R were inversely correlated to the miR-503 levels in the HCC tissues. Thus, we demonstrate that miR-503 inhibits the proliferation and induces the apoptosis of HCC cells, partly at least, by directly targeting IGF-1R, and suggest that IGF-1R may serve as a promising target for the treatment of HCC. PMID:27366090

  3. Inhibition by somatostatin (growth-hormone release-inhibiting hormone, GH-RIH) of gastric acid and pepsin and G-cell release of gastrin.

    PubMed Central

    Barros D'sa, A A; Bloom, S R; Baron, J H

    1978-01-01

    Somatostatin (cyclic growth-hormone release-inhibiting hormone--GH-RIH) was infused into dogs with gastric fistulae. Somatostatin inhibited gastric acid response to four gastric stimulants--insulin, food, histamine, and pentagastrin. Histamine- and pentagastrin-stimulated pepsins were inhibited similarly to inhibition of acid. Somatostatin inhibited the gastrin response to insulin and food. PMID:348581

  4. Inhibition of bacterial, fungal and plant growth by testa extracts of Citrullus genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Watermelon (Citrullus lanatus var. lanatus (Thunb.) Matsum & Nakai) seed exudates inhibit germination and seedling growth of several plant species and growth of pathogenic fungi and bacteria. This study was conducted to determine if extractable components in testae contribute to the inhibition. T...

  5. Interaction of TiO2 nanoparticles with the marine microalga Nitzschia closterium: growth inhibition, oxidative stress and internalization.

    PubMed

    Xia, Bin; Chen, Bijuan; Sun, Xuemei; Qu, Keming; Ma, Feifei; Du, Meirong

    2015-03-01

    The toxicity of TiO2 engineered nanoparticles (NPs) to the marine microalga Nitzschia closterium was investigated by examining growth inhibition, oxidative stress and uptake. The results indicated that the toxicity of TiO2 particles to algal cells significantly increased with decreasing nominal particle size, which was evidenced by the 96 EC50 values of 88.78, 118.80 and 179.05 mg/L for 21 nm, 60 nm and 400 nm TiO2 particles, respectively. The growth rate was significantly inhibited when the alga was exposed to 5mg/L TiO2 NPs (21 nm). Measurements of antioxidant enzyme activities showed that superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities were first induced and subsequently inhibited following exposure to 5mg/L TiO2 NPs. The depletion of antioxidant enzymes with a concomitant increase in malondialdehyde (MDA) levels and reactive oxygen species (ROS) posed a hazard to membrane integrity. A combination of flow cytometry analysis, transmission electron microscopy and Ti content measurement indicated that TiO2 NPs were internalized in N. closterium cells. The level of extracellular ROS, which was induced by TiO2 NPs under visible light, was negligible when compared with the intracellular ROS level (accounting for less than 6.0% of the total ROS level). These findings suggest that elevated TiO2 nanotoxicity in marine environments is related to increased ROS levels caused by internalization of TiO2 NPs. PMID:25483108

  6. Fluorescent minerals - A potential source of UV protection and visible light for the growth of green algae and cyanobacteria in extreme cosmic environments

    NASA Astrophysics Data System (ADS)

    Omairi, Tareq; Wainwright, Milton

    2015-07-01

    We propose that green algae (Chlorella variabilis and Dunaliella tertiolecta) and cyanobacteria (Synechococcus elongatus and Nostoc commune) can grow inside fluorescent rock minerals which convert damaging UV light to visible light, thereby allowing these organisms to survive and thrive in UV-rich environments without (or with limited) visible light, which would otherwise be inimical to them. The four microorganisms were incubated inside fluorescent rocks composed of fluorite, calcite and pyrite. The resultant growth was then measured following exposure to UV radiation, with the use of optical density and measurement of chlorophyll concentration. Results show that the microorganisms were shielded from harmful UV in these semi-transparent rocks, while at the same time benefiting from the fact that the minerals converted UV to visible light; this have been shown by a statistically significant increase in their growth, which although lower than when the cells were incubated in sunlight, was significantly higher than in controls incubated in the dark.

  7. Fluorescent minerals--A potential source of UV protection and visible light for the growth of green algae and cyanobacteria in extreme cosmic environments.

    PubMed

    Omairi, Tareq; Wainwright, Milton

    2015-07-01

    We propose that green algae (Chlorella variabilis and Dunaliella tertiolecta) and cyanobacteria (Synechococcus elongatus and Nostoc commune) can grow inside fluorescent rock minerals which convert damaging UV light to visible light, thereby allowing these organisms to survive and thrive in UV-rich environments without (or with limited) visible light, which would otherwise be inimical to them. The four microorganisms were incubated inside fluorescent rocks composed of fluorite, calcite and pyrite. The resultant growth was then measured following exposure to UV radiation, with the use of optical density and measurement of chlorophyll concentration. Results show that the microorganisms were shielded from harmful UV in these semi-transparent rocks, while at the same time benefiting from the fact that the minerals converted UV to visible light; this have been shown by a statistically significant increase in their growth, which although lower than when the cells were incubated in sunlight, was significantly higher than in controls incubated in the dark. PMID:26256632

  8. Laboratory study on the ecological impact of sophorolipid used for harmful algae elimination

    NASA Astrophysics Data System (ADS)

    Sun, Xiaoxia; Kim, Eunki; Sun, Song

    2010-11-01

    We studied the role of sophorolipid in inhibiting harmful algae bloom (HAB). Different sophorolipid concentrations were tested on marine microalgae, zooplankton, fish, and bivalve ( Mytilus edulis) in laboratory. The result shows that sophorolipid could inhibit the growth of algal species selectively. Among three algae species selected, Platymonas helgolandica var. tsingtaoensis was promoted with increasing sophorolipid concentration; Isochrysis galbana was inhibited seven days later in sophorolipid concentration below 40 mg/L; and Nitzschia closterium f. minutissima was inhibited obviously in only a high sophorolipid concentration over 20 mg/L. Therefore, sophorolipid in a low concentration at <20 mg/L could remove certain harmful algae species effectively without harming other non-harmful microalgae. For other animals, sophorolipid could inhibit the growth of ciliate Strombidium sp. by 50% at 20 mg/L sophorolipid concentration after 96 h. The concentration in 96-h LC50 for Calanus sinicus, Neomysis awatschensis, Lateolabrax japonicus, and Paralichthys olivaceus was 15, 150, 60, and 110 mg/L, respectively. The 24 h LC50 value for Artemia salina was 600 mg/L. The relative clearance rate of mussel Mytilus edulis decreased to 80%, 40%, and 20% of the control group after being exposed to 20, 50, and 100 mg/L sophorolipid for 24 h. Therefore, the toxicity for mitigation of harmful algae bloom at previously recommended concentration of 5-20 mg/L sophorolipid is low for most tested organisms in this reaserch.

  9. XET Activity is Found Near Sites of Growth and Cell Elongation in Bryophytes and Some Green Algae: New Insights into the Evolution of Primary Cell Wall Elongation

    PubMed Central

    Van Sandt, Vicky S. T.; Stieperaere, Herman; Guisez, Yves; Verbelen, Jean-Pierre; Vissenberg, Kris

    2007-01-01

    Background and Aims In angiosperms xyloglucan endotransglucosylase (XET)/hydrolase (XTH) is involved in reorganization of the cell wall during growth and development. The location of oligo-xyloglucan transglucosylation activity and the presence of XTH expressed sequence tags (ESTs) in the earliest diverging extant plants, i.e. in bryophytes and algae, down to the Phaeophyta was examined. The results provide information on the presence of an XET growth mechanism in bryophytes and algae and contribute to the understanding of the evolution of cell wall elongation in general. Methods Representatives of the different plant lineages were pressed onto an XET test paper and assayed. XET or XET-related activity was visualized as the incorporation of fluorescent signal. The Physcomitrella genome database was screened for the presence of XTHs. In addition, using the 3′ RACE technique searches were made for the presence of possible XTH ESTs in the Charophyta. Key Results XET activity was found in the three major divisions of bryophytes at sites corresponding to growing regions. In the Physcomitrella genome two putative XTH-encoding cDNA sequences were identified that contain all domains crucial for XET activity. Furthermore, XET activity was located at the sites of growth in Chara (Charophyta) and Ulva (Chlorophyta) and a putative XTH ancestral enzyme in Chara was identified. No XET activity was identified in the Rhodophyta or Phaeophyta. Conclusions XET activity was shown to be present in all major groups of green plants. These data suggest that an XET-related growth mechanism originated before the evolutionary divergence of the Chlorobionta and open new insights in the evolution of the mechanisms of primary cell wall expansion. PMID:17098750

  10. Negative Impact on Growth and Photosynthesis in the Green Alga Chlamydomonas reinhardtii in the Presence of the Estrogen 17α-Ethynylestradiol

    PubMed Central

    Pocock, Tessa; Falk, Stefan

    2014-01-01

    It is well known that estrogenic compounds affect development of fertilized eggs of many species of birds, fish and amphibians through disrupted activity of carbonic anhydrase (CA). The most potent activity comes from the most commonly occurring synthetic sterol, 17α-Ethynylestradiol (EE2). Less is known about the responses of aquatic phytoplankton to these compounds. Here we show for the first time that, in comparision to the control, the addition of 7 µM EE2 reduced the growth rate of the green alga Chlamydomonas reinhardtii by 68% for cells grown at high CO2. When cells were grown in ambient air (low Ci) with a fully activated carbon concentrating mechanism through the induction of CA activity, the growth rates were reduced by as much as 119%. A reduced growth rate could be observed at EE2 concentrations as low as 10 pM. This was accompanied by a reduced maximum capacity for electron transport in photosystem II as determined by a lower FV/FM for low Ci-grown cells, which indicates the involvement of CAH3, a CA specifically located in the thylakoid lumen involved in proton pumping across the thylakoid membranes. These results were in agreement with an observed reduction in the chloroplastic affinity for Ci as shown by a strong increase in the Michaelis-Menten K0.5 for HCO3−. In itself, a lowering of the growth rate of a green alga by addition of the sterol EE2 warrants further investigation into the potential environmental impact by the release of treated waste water. PMID:25310092

  11. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    SciTech Connect

    Hannon, Patrick R. Brannick, Katherine E. Wang, Wei Gupta, Rupesh K. Flaws, Jodi A.

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  12. Oligotrophic Bacteria Enhance Algal Growth under Iron-Deficient Conditions

    PubMed Central

    Keshtacher-Liebso..., E.; Hadar, Y.; Chen, Y.

    1995-01-01

    A Halomonas sp., a marine halophilic and oligotrophic bacterium, was grown on exudates of Dunaliella bardawil. The bacteria increased the solubility of Fe, thereby enhancing its availability to the algae. As a result, the algal growth rate increased. Because of these syntrophic relations, growth of the marine alga D. bardawil was facilitated at Fe levels that would otherwise induce Fe deficiency and inhibit algal growth. PMID:16535058

  13. Growth hormone receptor inhibition decreases the growth and metastasis of pancreatic ductal adenocarcinoma

    PubMed Central

    Subramani, Ramadevi; Lopez-Valdez, Rebecca; Salcido, Alyssa; Boopalan, Thiyagarajan; Arumugam, Arunkumar; Nandy, Sushmita; Lakshmanaswamy, Rajkumar

    2014-01-01

    Pancreatic cancer is the only major cancer with very low survival rates (1%). It is the fourth leading cause of cancer-related death. Hyperactivated growth hormone receptor (GHR) levels have been shown to increase the risk of cancer in general and this pathway is a master regulator of key cellular functions like proliferation, apoptosis, differentiation, metastasis, etc. However, to date there is no available data on how GHR promotes pancreatic cancer pathogenesis. Here, we used an RNA interference approach targeted to GHR to determine whether targeting GHR is an effective method for controlling pancreatic cancer growth and metastasis. For this, we used an in vitro model system consisting of HPAC and PANC-1 pancreatic cancer cells lines. GHR is upregulated in both of these cell lines and silencing GHR significantly reduced cell proliferation and viability. Inhibition of GHR also reduced the metastatic potential of pancreatic cancer cells, which was aided through decreased colony-forming ability and reduced invasiveness. Flow cytometric and western blot analyses revealed the induction of apoptosis in GHR silenced cells. GHR silencing affected phosphatidylinositol 3 kinase/AKT, mitogen extracellular signal-regulated kinase/extracellular signal-regulated kinase, Janus kinase/signal transducers and activators of transcription and mammalian target of rapamycin signaling, as well as, epithelial to mesenchymal transition. Interestingly, silencing GHR also suppressed the expression of insulin receptor-β and cyclo-oxygenease-2. Altogether, GHR silencing controls the growth and metastasis of pancreatic cancer and reveals its importance in pancreatic cancer pathogenesis. PMID:25301264

  14. Isolation and properties of fungi that lyse blue-green algae.

    PubMed Central

    Redhead, K; Wright, S J

    1978-01-01

    Of 70 pure microbial cultures isolated from aquatic habitats, soil, and air according to the ability to lyse live blue-green algae, 62 were fungi representing the genera Acremonium, Emericellopsis, and Verticillium. Algal-lysing fungi were isolated from all habitat types sampled. The remaining isolates comprised four bacteria and four streptomycetes. All isolates lysed Anabaena flos-aquae and, in most cases, several other filamentous and unicellular blue-green algae. The fungi generally showed greater activity than most other isolates towards a wider range of susceptible algae, including green algae in some cases. Acremonium and Emericellopsis isolates, but not Verticillium, also inhibited the growth of blue-green algae and gram-positive bacteria, but did not lyse the latter. Lysis of blue green algae by Acremonium and Emericellopsis spp. was associated with the formation of diffusible heat-stable extracellular factors which, evidence suggests, could be cephalosporin antibiotic(s). Blue-green algae were also lysed by pure cephalosporin C. The frequent isolation of lytic fungi from algal habitats suggests a possible natural algal-destroying role for such fungi, which might be exploitable for algal bloom control. Images PMID:418740

  15. Dual inhibition of cyclooxygenase-2 and soluble epoxide hydrolase synergistically suppresses primary tumor growth and metastasis

    PubMed Central

    Zhang, Guodong; Panigrahy, Dipak; Hwang, Sung Hee; Yang, Jun; Mahakian, Lisa M.; Wettersten, Hiromi I.; Liu, Jun-Yan; Wang, Yanru; Ingham, Elizabeth S.; Tam, Sarah; Kieran, Mark W.; Weiss, Robert H.; Ferrara, Katherine W.; Hammock, Bruce D.

    2014-01-01

    Prostaglandins derived from the cyclooxygenase (COX) pathway and epoxyeicosatrienoic acids (EETs) from the cytochrome P450/soluble epoxide hydrolase (sEH) pathway are important eicosanoids that regulate angiogenesis and tumorigenesis. COX-2 inhibitors, which block the formation of prostaglandins, suppress tumor growth, whereas sEH inhibitors, which increase endogenous EETs, stimulate primary tumor growth and metastasis. However, the functional interactions of these two pathways in cancer are unknown. Using pharmacological inhibitors as probes, we show here that dual inhibition of COX-2 and sEH synergistically inhibits primary tumor growth and metastasis by suppressing tumor angiogenesis. COX-2/sEH dual pharmacological inhibitors also potently suppress primary tumor growth and metastasis by inhibiting tumor angiogenesis via selective inhibition of endothelial cell proliferation. These results demonstrate a critical interaction of these two lipid metabolism pathways on tumorigenesis and suggest dual inhibition of COX-2 and sEH as a potential therapeutic strategy for cancer therapy. PMID:25024195

  16. Effects of salts on the halophilic alga Dunaliella viridis.

    PubMed

    Johnson, M K; Johnson, E J; MacElroy, R D; Speer, H L; Bruff, B S

    1968-04-01

    Determinations of the salt sensitivity of enzymes extracted from the halophilic alga Dunaliella viridis revealed that pentose phosphate isomerase, ribulose diphosphate carboxylase, glucose-6-phosphate dehydrogenase, and phosphohexose isomerase were inhibited by NaCl concentrations far lower than that in the growth medium (3.75 m). The inhibition was reversible and was not prevented by preparing the extracts in the presence of salt. Potassium, lithium, and cesium chlorides were equally inhibitory. In contrast, whole cells require rather high levels of NaCl for optimal growth, whereas growth is inhibited by low levels of the other cations. The results suggest a specific mechanism for the exclusion of sodium from the interior of the cell. PMID:5646631

  17. Galactose inhibits auxin-induced growth of Avena coleoptiles by two mechanisms

    NASA Technical Reports Server (NTRS)

    Cheung, S. P.; Cleland, R. E.

    1991-01-01

    Galactose inhibits auxin-induced growth of Avena coleoptiles by at least two mechanisms. First, it inhibits auxin-induced H(+)-excretion needed for the initiation of rapid elongation. Galactose cannot be doing so by directly interfering with the ATPase since fusicoccin-induced H(+)-excretion is not affected. Secondly, galactose inhibits long-term auxin-induced growth, even in an acidic (pH 4.5) solution. This may be due to an inhibition of cell wall synthesis. However, galactose does not reduce the capacity of walls to be loosened by H+, given exogenously or excreted in response to fusicoccin.

  18. Polymer film deposition on agar using a dielectric barrier discharge jet and its bacterial growth inhibition

    NASA Astrophysics Data System (ADS)

    Tsai, T.-C.; Cho, J.; Mcintyre, K.; Jo, Y.-K.; Staack, D.

    2012-08-01

    Polymer film deposition on agar in ambient air was achieved using the helium dielectric barrier discharge jet (DBD jet) fed with polymer precursors, and the bacterial growth inhibition due to the deposited film was observed. The DBD jet with precursor addition was more efficient at sterilization than a helium-only DBD jet. On the areas where polymer films cover the agar the bacterial growth was significantly inhibited. The inhibition efficacy showed dependence on the film thickness. The DBD jet without precursor also created a modified agar layer, which may slow the growth of some bacterial strains.

  19. Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107.

    PubMed

    Barbie, Thanh U; Barbie, David A; MacLaughlin, David T; Maheswaran, Shyamala; Donahoe, Patricia K

    2003-12-23

    In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might also respond to MIS. A number of cervical cancer cell lines express the MIS type II receptor, and MIS inhibits the growth of both human papilloma virus-transformed and non-human papilloma virus-transformed cervical cell lines, with a more dramatic effect seen in the latter. As in the ovarian cancer cell line OVCAR8, suppression of growth of the C33A cervical cancer cell line by MIS is associated with induction of the p16 tumor suppressor protein. However, in contrast to OVCAR8 cells, induction of p130 and p107 appears to play an important role in the inhibition of growth of C33A cells by MIS. Finally, normal cervical tissue expresses the MIS type II receptor in vivo, supporting the idea that MIS could be a targeted therapy for cervical cancer. PMID:14671316

  20. Pyomelanin is produced by Shewanella algae BrY and affected by exogenous iron.

    PubMed

    Turick, Charles E; Caccavo, Frank; Tisa, Louis S

    2008-04-01

    Melanin production by Shewanella algae BrY occurred during late- and (or) post-exponential growth in lactate basal salts liquid medium supplemented with tyrosine or phenylalanine. The antioxidant ascorbate inhibited melanin production but not production of the melanin precursor homogentisic acid. In the absence of ascorbate, melanin production was inhibited by the 4-hydroxyphenylpyruvate dioxygenase inhibitor sulcotrione and by concentrations of Fe >or= 0.38 mmol L(-1). These data support the hypothesis that pigment production by S. algae BrY was a result of the conversion of tyrosine or phenylalanine to homogentisic acid, which was excreted, auto-oxidized, and self-polymerized to form pyomelanin. Pyomelanin production by S. algae BrY may play an important role in the biogeochemical cycling of Fe in the environment. PMID:18389008

  1. Bismuth(III) deferiprone effectively inhibits growth of Desulfovibrio desulfuricans ATCC 27774.

    PubMed

    Barton, Larry L; Lyle, Daniel A; Ritz, Nathaniel L; Granat, Alex S; Khurshid, Ali N; Kherbik, Nada; Hider, Robert; Lin, Henry C

    2016-04-01

    Sulfate-reducing bacteria have been implicated in inflammatory bowel diseases and ulcerative colitis in humans and there is an interest in inhibiting the growth of these sulfide-producing bacteria. This research explores the use of several chelators of bismuth to determine the most effective chelator to inhibit the growth of sulfate-reducing bacteria. For our studies, Desulfovibrio desulfuricans ATCC 27774 was grown with nitrate as the electron acceptor and chelated bismuth compounds were added to test for inhibition of growth. Varying levels of inhibition were attributed to bismuth chelated with subsalicylate or citrate but the most effective inhibition of growth by D. desulfuricans was with bismuth chelated by deferiprone, 3-hydroxy-1,2-dimethyl-4(1H)-pyridone. Growth of D. desulfuricans was inhibited by 10 μM bismuth as deferiprone:bismuth with either nitrate or sulfate respiration. Our studies indicate deferiprone:bismuth has bacteriostatic activity on D. desulfuricans because the inhibition can be reversed following exposure to 1 mM bismuth for 1 h at 32 °C. We suggest that deferiprone is an appropriate chelator for bismuth to control growth of sulfate-reducing bacteria because deferiprone is relatively nontoxic to animals, including humans, and has been used for many years to bind Fe(III) in the treatment of β-thalassemia. PMID:26896170

  2. Effect of Trichoderma on plant growth: A balance between inhibition and growth promotion.

    PubMed

    Ousley, M A; Lynch, J M; Whipps, J M

    1993-11-01

    The effect of lettuce (Latuca sativa L.) germination and growth in nonsterilized potting compost of 0.1% and 1.0% w/w incorporation of fermenter biomass inocula of six strains of Trichoderma was investigated. Except for strains WT and T35 at 0.1 % w/w, all inocula inhibited germination. Biomass of strains WT, T35, 20, and 47 at 1.0% promoted shoot fresh weight, whereas strains TH1 and 8MF2 were inhibitory. In contrast, when biomass of strains WT, TH1, and 8MF2 was autoclaved and incorporated at 1%, shoot fresh weight was promoted, but the biomass of T35 was inhibitory. None of the strains incorporated at 0.1 % w/w increased shoot fresh weight, and autoclaved biomass of TH1, T35, and 20 incorporated at 0.1% w/w resulted in lower shoot fresh weights in comparison with uninoculated controls. The shoot dry weight of lettuce seedlings could be enhanced by germinating seeds in uninoculated compost and after five days' growth transferring them into WT-inoculated compost. Inoculum of strain TH1 when applied using this method was very inhibitory. With WT the degree of increase in shoot fresh weight and germination rate declined as the fermentation time to produce inocula was increased. PMID:24190096

  3. A chemical pollen suppressant inhibits auxin-induced growth in maize coleoptile sections

    SciTech Connect

    Vesper, M.J. ); Cross, J.W. )

    1990-05-01

    Chemical inhibitors of pollen development having a phenylcinnoline carboxylate structure were found to inhibit IAA- and 1-NAA-induced growth in maize coleoptile sections. The inhibitor (100 {mu}M) used in these experiments caused approx. 35% reduction in auxin-induced growth over the auxin concentration range of 0.3 to 100 {mu}M. Growth inhibition was noted as a lengthening of the latent period and a decrease in the rate of an auxin-induced growth response. An acid growth response to pH 5 buffer in abraded sections was not impaired. The velocity of basipetal transport of ({sup 3}H)IAA through the coleoptile sections also was not inhibited by the compound, nor was uptake of ({sup 3}H)IAA. Similarly, the inhibitor does not appear to alter auxin-induced H{sup +} secretion. We suggest that the agent targets some other process necessary for auxin-dependent growth.

  4. Inhibition of the growth of cyanobacteria during the recruitment stage in Lake Taihu.

    PubMed

    Lu, Yaping; Wang, Jin; Zhang, Xiaoqian; Kong, Fanxiang

    2016-03-01

    Microcystis is the dominant algal bloom genus in Lake Taihu. Thus, controlling the recruitment and growth of Microcystis is the most crucial aspect of solving the problem of algal blooms. Different concentrations (0.025, 0.05, and 0.1 g L(-1)) of tea extract were used to treat barrels of lake water at the recruitment stage of cyanobacteria. There was an inhibitory effect on algal growth in all treatment groups. The inhibitory effect on cyanobacteria was stronger than on other algae. The metabolic activity of cells in the treatment groups was significantly enhanced compared to the control, as an adaptation to the stress caused by tea polyphenols. The photosynthetic activity diminished in the treatment groups and was barely detected in the 0.05 and 0.1 g L(-1) treatments. The levels of reactive oxygen species increased substantially in treated cells with the algal cells experiencing oxidative damage. The effect of tea on zooplankton was also studied. The number of Bosmina fatalis individuals did not change significantly in the 0.025 and 0.05 g L(-1) treatments. These results suggested that the application of tea extracts, during the recruitment stage of blue-green algae, suppressed the recruitment and growth of cyanobacteria, thus offering the potential to prevent cyanobacterial blooms. PMID:26590061

  5. Inhibition of Diabrotica Larval Growth by Patatin, the Lipid Acyl Hydrolase from Potato Tubers.

    PubMed Central

    Strickland, J. A.; Orr, G. L.; Walsh, T. A.

    1995-01-01

    Patatin, the nonspecific lipid acyl hydrolase from potato (Solanum tuberosum L.) tubers, dose-dependently inhibits the growth of southern corn rootworm (SCR) and western corn rootworm when fed to them on artificial diet. The 50% growth reduction levels are somewhat cultivar dependent, ranging from 60 to 150 [mu]g/g diet for neonate SCR larvae. A single patatin isoform also inhibits larval growth. Neonate SCR continuously exposed to patatin are halted in larval development. Treatment with di-isopropylfluorophosphate essentially eliminates patatin's phospholipase, galactolipase, and acyl hydrolase activities. SCR growth inhibition is eliminated also, indicating that patatin's serine hydrolase activity is responsible for the observed activities. Patatin-mediated phospholipolysis is highly pH and cultivar dependent, with specific activities up to 300-fold less at pH 5.5 than at pH 8.5. Esterase or phospholipase activities do not correlate with insect growth inhibition. Galactolipase activity, being cultivar and pH independent, correlates significantly with SCR growth inhibition. Insect-growth inhibition of patatin is significantly reduced with increased dietary cholesterol levels. In conclusion, patatin represents a new class of insect-control proteins with a novel mode of action possibly involving lipid metabolism. PMID:12228621

  6. Inhibition of Diabrotica Larval Growth by Patatin, the Lipid Acyl Hydrolase from Potato Tubers.

    PubMed

    Strickland, J. A.; Orr, G. L.; Walsh, T. A.

    1995-10-01

    Patatin, the nonspecific lipid acyl hydrolase from potato (Solanum tuberosum L.) tubers, dose-dependently inhibits the growth of southern corn rootworm (SCR) and western corn rootworm when fed to them on artificial diet. The 50% growth reduction levels are somewhat cultivar dependent, ranging from 60 to 150 [mu]g/g diet for neonate SCR larvae. A single patatin isoform also inhibits larval growth. Neonate SCR continuously exposed to patatin are halted in larval development. Treatment with di-isopropylfluorophosphate essentially eliminates patatin's phospholipase, galactolipase, and acyl hydrolase activities. SCR growth inhibition is eliminated also, indicating that patatin's serine hydrolase activity is responsible for the observed activities. Patatin-mediated phospholipolysis is highly pH and cultivar dependent, with specific activities up to 300-fold less at pH 5.5 than at pH 8.5. Esterase or phospholipase activities do not correlate with insect growth inhibition. Galactolipase activity, being cultivar and pH independent, correlates significantly with SCR growth inhibition. Insect-growth inhibition of patatin is significantly reduced with increased dietary cholesterol levels. In conclusion, patatin represents a new class of insect-control proteins with a novel mode of action possibly involving lipid metabolism. PMID:12228621

  7. Tumour growth inhibition and anti-angiogenic effects using curcumin correspond to combined PDE2 and PDE4 inhibition.

    PubMed

    Abusnina, Abdurazzag; Keravis, Thérèse; Zhou, Qingwei; Justiniano, Hélène; Lobstein, Annelise; Lugnier, Claire

    2015-02-01

    Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis by stimulating endothelial cells. Increase in cyclic AMP (cAMP) level inhibits VEGF-induced endothelial cell proliferation and migration. Cyclic nucleotide phosphodiesterases (PDEs), which specifically hydrolyse cyclic nucleotides, are critical in the regulation of this signal transduction. We have previously reported that PDE2 and PDE4 up-regulations in human umbilical vein endothelial cells (HUVECs) are implicated in VEGF-induced angiogenesis and that inhibition of PDE2 and PDE4 activities prevents the development of the in vitro angiogenesis by increasing cAMP level, as well as the in vivo chicken embryo angiogenesis. We have also shown that polyphenols are able to inhibit PDEs. The curcumin having anti-cancer properties, the present study investigated whether PDE2 and PDE4 inhibitors and curcumin could have similar in vivo anti-tumour properties and whether the anti-angiogenic effects of curcumin are mediated by PDEs. Both PDE2/PDE4 inhibitor association and curcumin significantly inhibited in vivo tumour growth in C57BL/6N mice. In vitro, curcumin inhibited basal and VEGF-stimulated HUVEC proliferation and migration and delayed cell cycle progression at G0/G1, similarly to the combination of selective PDE2 and PDE4 inhibitors. cAMP levels in HUVECs were significantly increased by curcumin, similarly to rolipram (PDE4 inhibitor) and BAY-60-550 (PDE2 inhibitor) association, indicating cAMP-PDE inhibitions. Moreover, curcumin was able to inhibit VEGF-induced cAMP-PDE activity without acting on cGMP-PDE activity and to modulate PDE2 and PDE4 expressions in HUVECs. The present results suggest that curcumin exerts its in vitro anti-angiogenic and in vivo anti-tumour properties through combined PDE2 and PDE4 inhibition. PMID:25230992

  8. Gellan sulfate inhibits Plasmodium falciparum growth and invasion of red blood cells in vitro.

    PubMed

    Recuenco, Frances Cagayat; Kobayashi, Kyousuke; Ishiwa, Akiko; Enomoto-Rogers, Yukiko; Fundador, Noreen Grace V; Sugi, Tatsuki; Takemae, Hitoshi; Iwanaga, Tatsuya; Murakoshi, Fumi; Gong, Haiyan; Inomata, Atsuko; Horimoto, Taisuke; Iwata, Tadahisa; Kato, Kentaro

    2014-01-01

    Here, we assessed the sulfated derivative of the microbial polysaccharide gellan gum and derivatives of λ and κ-carrageenans for their ability to inhibit Plasmodium falciparum 3D7 and Dd2 growth and invasion of red blood cells in vitro. Growth inhibition was assessed by means of flow cytometry after a 96-h exposure to the inhibitors and invasion inhibition was assessed by counting ring parasites after a 20-h exposure to them. Gellan sulfate strongly inhibited invasion and modestly inhibited growth for both P. falciparum 3D7 and Dd2; both inhibitory effects exceeded those achieved with native gellan gum. The hydrolyzed λ-carrageenan and oversulfated κ-carrageenan were less inhibitory than their native forms. In vitro cytotoxicity and anticoagulation assays performed to determine the suitability of the modified polysaccharides for in vivo studies showed that our synthesized gellan sulfate had low cytotoxicity and anticoagulant activity. PMID:24740150

  9. In vitro mechanism of inhibition of bacterial cell growth by allicin.

    PubMed Central

    Feldberg, R S; Chang, S C; Kotik, A N; Nadler, M; Neuwirth, Z; Sundstrom, D C; Thompson, N H

    1988-01-01

    Diallyl thiosulfinate (allicin) is the agent found in garlic which is responsible for the antibacterial and antifungal activity of extracts of this plant. The effect of bacteriostatic concentrations of allicin (0.2 to 0.5 mM) on the growth of Salmonella typhimurium revealed a pattern of inhibition characterized by: (i) a lag of approximately 15 min between addition of allicin and onset of inhibition, (ii) a transitory inhibition phase whose duration was proportional to allicin concentration and inversely proportional to culture density, (iii) a resumed growth phase which showed a lower rate of growth than in uninhibited controls, and (iv) an entry into stationary phase at a lower culture density. Whereas DNA and protein syntheses showed a delayed and partial inhibition by allicin, inhibition of RNA synthesis was immediate and total, suggesting that this is the primary target of allicin action. PMID:2469386

  10. Gellan sulfate inhibits Plasmodium falciparum growth and invasion of red blood cells in vitro

    PubMed Central

    Recuenco, Frances Cagayat; Kobayashi, Kyousuke; Ishiwa, Akiko; Enomoto-Rogers, Yukiko; Fundador, Noreen Grace V.; Sugi, Tatsuki; Takemae, Hitoshi; Iwanaga, Tatsuya; Murakoshi, Fumi; Gong, Haiyan; Inomata, Atsuko; Horimoto, Taisuke; Iwata, Tadahisa; Kato, Kentaro

    2014-01-01

    Here, we assessed the sulfated derivative of the microbial polysaccharide gellan gum and derivatives of λ and κ-carrageenans for their ability to inhibit Plasmodium falciparum 3D7 and Dd2 growth and invasion of red blood cells in vitro. Growth inhibition was assessed by means of flow cytometry after a 96-h exposure to the inhibitors and invasion inhibition was assessed by counting ring parasites after a 20-h exposure to them. Gellan sulfate strongly inhibited invasion and modestly inhibited growth for both P. falciparum 3D7 and Dd2; both inhibitory effects exceeded those achieved with native gellan gum. The hydrolyzed λ-carrageenan and oversulfated κ-carrageenan were less inhibitory than their native forms. In vitro cytotoxicity and anticoagulation assays performed to determine the suitability of the modified polysaccharides for in vivo studies showed that our synthesized gellan sulfate had low cytotoxicity and anticoagulant activity. PMID:24740150

  11. Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts

    SciTech Connect

    Sandler, Charlotta; Joutsiniemi, Saima; Lindstedt, Ken A.; Juutilainen, Timo; Kovanen, Petri T.; Eklund, Kari K. . E-mail: kari.eklund@hus.fi

    2006-08-18

    Synovial fibroblast is the key cell type in the growth of the pathological synovial tissue in arthritis. Here, we show that platelet-derived growth factor (PDGF) is a potent mitogen for synovial fibroblasts isolated from patients with rheumatoid arthritis. Inhibition of PDGF-receptor signalling by imatinib mesylate (1 {mu}M) completely abrogated the PDGF-stimulated proliferation and inhibited approximately 70% of serum-stimulated proliferation of synovial fibroblasts. Similar extent of inhibition was observed when PDGF was neutralized with anti-PDGF antibodies, suggesting that imatinib mesylate does not inhibit pathways other than those mediated by PDGF-receptors. No signs of apoptosis were detected in synovial fibroblasts cultured in the presence of imatinib. These results suggest that imatinib mesylate specifically inhibits PDGF-stimulated proliferation of synovial fibroblasts, and that inhibition of PDGF-receptors could represent a feasible target for novel antirheumatic therapies.

  12. Inhibition of Plasmodium falciparum dihydropteroate synthetase and growth in vitro by sulfa drugs.

    PubMed Central

    Zhang, Y; Meshnick, S R

    1991-01-01

    The Michaelis-Menten inhibitory constants (Kis) and the concentrations required for 50% inhibition of the Plasmodium falciparum dihydropteroate synthetase were determined for six sulfa drugs. These drugs inhibited the in vitro growth of P. falciparum (50% lethal concentration) at concentrations of 30 to 500 nM; these concentrations were 100 to 1,000 times lower than the concentrations required for 50% inhibition and Kis (6 to 500 microM). The uptake of p-aminobenzoic acid was not inhibited by the sulfa drugs. However, infected erythrocytes took up more labeled sulfamethoxazole than did uninfected erythrocytes. Thus, the concentration of sulfa drugs by malaria parasites may explain how sulfa drugs inhibit in vitro growth of parasites through the inhibition of dihydropteroate synthetase. PMID:2024960

  13. Ability of Cecal Cultures to Inhibit Growth of Salmonella Typhimurium during Aerobic Incubation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Poultry can serve as reservoirs for Salmonella; however, chicks provided cultures of cecal bacteria develop resistance to colonization by Salmonella. Research has indicated that cecal bacteria metabolize organic acids to produce substances that inhibit Salmonella growth. Purpose: The...

  14. Inhibition of prostate cancer growth by muscadine grapeskin extract and resveratrol through distinct mechanisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phytochemicals are naturally occurring compounds with demonstrated anti-tumor activities. The phytochemical resveratrol, contained in red grapes, has been shown to inhibit prostate cancer cell growth, potentially through its anti-oxidant activity. Muscadine grapes contain different phytochemical con...

  15. Chloride anion transporters inhibit growth of methicillin-resistant Staphylococcus aureus (MRSA) in vitro.

    PubMed

    Share, Andrew I; Patel, Khushali; Nativi, Cristina; Cho, Eun J; Francesconi, Oscar; Busschaert, Nathalie; Gale, Philip A; Roelens, Stefano; Sessler, Jonathan L

    2016-06-18

    A series of aminopyrrolic receptors were tested as anion transporters using POPC liposome model membranes. Many were found to be effective Cl(-) transporters and to inhibit clinical strains of Staphylococcus aureus growth in vitro. The best transporters proved effective against the methicillin-resistant Staphylococcus aureus (MRSA) strains, Mu50 and HP1173. Tris-thiourea tren-based chloride transporters were also shown to inhibit the growth of S. aureus in vitro. PMID:27223254

  16. Inhibition of Growth of Salmonella by Native Flora of Broiler Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction Some bacteria in the cecal microflora of broilers can inhibit colonization of chicks by Salmonella. Beneficial cecal bacteria may reduce Salmonella colonization by competing for nutrients and attachment sites or by producing metabolites that inhibit Salmonella growth. The purpose of th...

  17. The FGF-2-Derived Peptide FREG Inhibits Melanoma Growth In Vitro and In Vivo

    PubMed Central

    Aguzzi, Maria S; Faraone, Debora; D'Arcangelo, Daniela; De Marchis, Francesco; Toietta, Gabriele; Ribatti, Domenico; Parazzoli, Alberto; Colombo, Paolo; Capogrossi, Maurizio C; Facchiano, Antonio

    2011-01-01

    Previous data report that fibroblast growth factor-2 (FGF-2)-derived peptide FREG potently inhibits FGF-2-dependent angiogenesis in vitro and in vivo. Here, we show that FREG inhibits up to 70% in vitro growth and invasion/migration of smooth muscle and melanoma cells. Such inhibition is mediated by platelet-derived growth factor-receptor-α (PDGF-Rα); in fact, proliferation and migration were restored upon PDGF-Rα neutralization. Further experiments demonstrated that FREG interacts with PDGF-Rα both in vitro and in vivo and stimulates its phosphorylation. We have previously shown that overexpressing PDGF-Rα strongly inhibits melanoma growth in vivo; we, therefore, hypothesized that PDGF-Rα agonists may represent a novel tool to inhibit melanoma growth in vivo. To support this hypothesis, FREG was inoculated intravenously (i.v.) in a mouse melanoma model and markedly inhibited pulmonary metastases formation. Immunohistochemical analyses showed less proliferation, less angiogenesis, and more apoptosis in metastasized lungs upon FREG treatment, as compared to untreated controls. Finally, in preliminary acute toxicity studies, FREG showed no toxicity signs in healthy animals, and neither microscopic nor macroscopic toxicity at the liver, kidney, and lungs level. Altogether, these data indicate that FREG systemic treatment strongly inhibits melanoma metastases development and indicate for the first time that agonists of PDGF-Rα may control melanoma both in vitro and in vivo. PMID:20924364

  18. Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate

    PubMed Central

    Goldman, Corey K.; Kendall, Richard L.; Cabrera, Gustavo; Soroceanu, Liliana; Heike, Yuji; Gillespie, G. Yancey; Siegal, Gene P.; Mao, Xianzhi; Bett, Andrew J.; Huckle, William R.; Thomas, Kenneth A.; Curiel, David T.

    1998-01-01

    Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth. PMID:9671758

  19. Culture at a Higher Temperature Mildly Inhibits Cancer Cell Growth but Enhances Chemotherapeutic Effects by Inhibiting Cell-Cell Collaboration

    PubMed Central

    Zhu, Shengming; Wang, Jiangang; Xie, Bingkun; Luo, Zhiguo; Lin, Xiukun; Liao, D. Joshua

    2015-01-01

    Acute febrile infections have historically been used to treat cancer. To explore the underlying mechanism, we studied chronic effects of fever on cancer cell growth and chemotherapeutic efficacy in cell culture. We found that culturing cancer cells at 39°C mildly inhibited cell growth by arresting the cells at the G1 phase of the cell cycle. When cells were seeded in culture dishes at a lower density, e.g. about 1000–2000 cells per 35-mm dish, the growth inhibition was much greater, manifested as many fewer cell colonies in the 39°C dishes, compared with the results at a higher density seeding, e.g. 20,000 cells per dish, suggesting that cell-cell collaboration as the Allee effect in cell culture is inhibited at 39°C. Withdrawal of cells from serum enhanced the G1 arrest at 39°C and, for some cell lines such as A549 lung cancer cells, serum replenishment failed to quickly drive the cells from the G1 into the S and G2-M phases. Therapeutic effects of several chemotherapeutic agents, including clove bud extracts, on several cancer cell lines were more potent at 39°C than at 37°C, especially when the cells were seeded at a low density. For some cell lines and some agents, this enhancement is long-lasting, i.e. continuing after the cessation of the treatment. Collectively these results suggest that hyperthermia may inhibit cancer cell growth by G1 arrest and by inhibition of cell-cell collaboration, and may enhance the efficacy of several chemotherapeutic agents, an effect which may persist beyond the termination of chemotherapy. PMID:26495849

  20. Culture at a Higher Temperature Mildly Inhibits Cancer Cell Growth but Enhances Chemotherapeutic Effects by Inhibiting Cell-Cell Collaboration.

    PubMed

    Zhu, Shengming; Wang, Jiangang; Xie, Bingkun; Luo, Zhiguo; Lin, Xiukun; Liao, D Joshua

    2015-01-01

    Acute febrile infections have historically been used to treat cancer. To explore the underlying mechanism, we studied chronic effects of fever on cancer cell growth and chemotherapeutic efficacy in cell culture. We found that culturing cancer cells at 39°C mildly inhibited cell growth by arresting the cells at the G1 phase of the cell cycle. When cells were seeded in culture dishes at a lower density, e.g. about 1000-2000 cells per 35-mm dish, the growth inhibition was much greater, manifested as many fewer cell colonies in the 39°C dishes, compared with the results at a higher density seeding, e.g. 20,000 cells per dish, suggesting that cell-cell collaboration as the Allee effect in cell culture is inhibited at 39°C. Withdrawal of cells from serum enhanced the G1 arrest at 39°C and, for some cell lines such as A549 lung cancer cells, serum replenishment failed to quickly drive the cells from the G1 into the S and G2-M phases. Therapeutic effects of several chemotherapeutic agents, including clove bud extracts, on several cancer cell lines were more potent at 39°C than at 37°C, especially when the cells were seeded at a low density. For some cell lines and some agents, this enhancement is long-lasting, i.e. continuing after the cessation of the treatment. Collectively these results suggest that hyperthermia may inhibit cancer cell growth by G1 arrest and by inhibition of cell-cell collaboration, and may enhance the efficacy of several chemotherapeutic agents, an effect which may persist beyond the termination of chemotherapy. PMID:26495849

  1. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles.

    PubMed

    Hannon, Patrick R; Brannick, Katherine E; Wang, Wei; Gupta, Rupesh K; Flaws, Jodi A

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1-100 μg/ml) for 24-96 h to establish the temporal effects of DEHP on the follicle. Following 24-96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. PMID:25701202

  2. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    PubMed Central

    Hannon, Patrick R.; Brannick, Katherine E.; Wang, Wei; Gupta, Rupesh K.; Flaws, Jodi A.

    2015-01-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1-100μg/ml) for 24-96 hr to establish the temporal effects of DEHP on the follicle. Following 24-96 hr of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydorxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. PMID:25701202

  3. Comparison of toxicity of class-based organic chemicals to algae and fish based on discrimination of excess toxicity from baseline level.

    PubMed

    Li, Jin J; Tai, Hong W; Yu, Yang; Wen, Yang; Wang, Xiao H; Zhao, Yuan H

    2015-07-01

    Toxicity data to fish and algae were used to investigate excess toxicity between species. Results show that chemicals exhibiting excess toxicity to fish also show excess toxicity to algae for most of the compounds. This indicates that they share the same mode of action between species. Similar relationships between logKOW and toxicities to fish and algae for baseline and less inert compounds suggest that they have similar critical body residues in the two species. Differences in excess toxicity for some compounds suggest that there is a difference of physiological structure and metabolism between fish and algae. Some reactive compounds (e.g. polyamines) exhibit greater toxic effects for algae than those for fish because of relatively low bio-uptake potential of these hydrophilic compounds in fish as compared with that in algae. Esters exhibiting greater toxicity in fish than that in algae indicate that metabolism can affect the discrimination of excess toxicity from baseline level. Algae growth inhibition is a very good surrogate for fish lethality. This is not only because overall toxicity sensitivity to algae is greater than that to fish, but also the excess toxicity calculated from algal toxicity can better reflect reactivity of compounds with target molecules than fish toxicity. PMID:26186523

  4. Nutritional And Taste Characteristics Of Algae

    NASA Technical Reports Server (NTRS)

    Karel, M.; Nakhost, Z.

    1992-01-01

    Report describes investigation of chemical composition of blue-green algae Synechococcus 6311, as well as preparation of protein isolate from green alga Scenedesmus obliquus and incorporation into variety of food products evaluated for taste. Part of program to investigate growth of microalgae aboard spacecraft for use as food.

  5. Effect of Dead Algae on Soil Permeability

    SciTech Connect

    Harvey, R.S.

    2003-02-21

    Since existing basins support heavy growths of unicellular green algae which may be killed by temperature variation or by inadvertent pH changes in waste and then deposited on the basin floor, information on the effects of dead algae on soil permeability was needed. This study was designed to show the effects of successive algal kills on the permeability of laboratory soil columns.

  6. Inhibition of the growth of Alexandrium tamarense by algicidal substances in Chinese fir (Cunninghamia lanceolata).

    PubMed

    Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye; Zhang, Xin-Lian; Qi, Yu-Zao

    2009-10-01

    The wood sawdust from Chinese fir (Cunninghamia lanceolata) exhibited stronger inhibition on the growth of Alexandrium tamarense than those from alder (Alnus cremastogyne), pine (Pinus massoniana), birch (Betula alnoides) and sapele (Entandrophragma cylindricum). The water extract, acetone-water extract and essential oil from fir sawdust were all shown to inhibit the growth of A. tamarense. The inhibition of fir essential oil was the strongest among all the above wood sources while the half effective concentration was only 0.65 mg/L. These results suggested that the fir essential oil may play an important role in the algicidal effect of Chinese fir. PMID:19634014

  7. BRD4 inhibitor inhibits colorectal cancer growth and metastasis.

    PubMed

    Hu, Yuan; Zhou, Jieqiong; Ye, Fei; Xiong, Huabao; Peng, Liang; Zheng, Zihan; Xu, Feihong; Cui, Miao; Wei, Chengguo; Wang, Xinying; Wang, Zhongqiu; Zhu, Hongfa; Lee, Peng; Zhou, Mingming; Jiang, Bo; Zhang, David Y

    2015-01-01

    Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal. PMID:25603177

  8. Ivermectin Inhibits Growth of Chlamydia trachomatis in Epithelial Cells

    PubMed Central

    Pettengill, Matthew A.; Lam, Verissa W.; Ollawa, Ikechukwu; Marques-da-Silva, Camila; Ojcius, David M.

    2012-01-01

    Ivermectin is currently approved for treatment of both clinical and veterinary infections by nematodes, including Onchocerca cervicalis in horses and Onchocerca volvulus in humans. However, ivermectin has never been shown to be effective against bacterial pathogens. Here we show that ivermectin also inhibits infection of epithelial cells by the bacterial pathogen, Chlamydia trachomatis, at doses that could be envisioned clinically for sexually-transmitted or ocular infections by Chlamydia. PMID:23119027

  9. Ivermectin inhibits growth of Chlamydia trachomatis in epithelial cells.

    PubMed

    Pettengill, Matthew A; Lam, Verissa W; Ollawa, Ikechukwu; Marques-da-Silva, Camila; Ojcius, David M

    2012-01-01

    Ivermectin is currently approved for treatment of both clinical and veterinary infections by nematodes, including Onchocerca cervicalis in horses and Onchocerca volvulus in humans. However, ivermectin has never been shown to be effective against bacterial pathogens. Here we show that ivermectin also inhibits infection of epithelial cells by the bacterial pathogen, Chlamydia trachomatis, at doses that could be envisioned clinically for sexually-transmitted or ocular infections by Chlamydia. PMID:23119027

  10. Growth Inhibition of Pathogenic Bacteria by Sulfonylurea Herbicides

    PubMed Central

    Kreisberg, Jason F.; Ong, Nicholas T.; Krishna, Aishwarya; Joseph, Thomas L.; Wang, Jing; Ong, Catherine; Ooi, Hui Ann; Sung, Julie C.; Siew, Chern Chiang; Chang, Grace C.; Biot, Fabrice; Cuccui, Jon; Wren, Brendan W.; Chan, Joey; Sivalingam, Suppiah P.; Zhang, Lian-Hui; Verma, Chandra

    2013-01-01

    Emerging resistance to current antibiotics raises the need for new microbial drug targets. We show that targeting branched-chain amino acid (BCAA) biosynthesis using sulfonylurea herbicides, which inhibit the BCAA biosynthetic enzyme acetohydroxyacid synthase (AHAS), can exert bacteriostatic effects on several pathogenic bacteria, including Burkholderia pseudomallei, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our results suggest that targeting biosynthetic enzymes like AHAS, which are lacking in humans, could represent a promising antimicrobial drug strategy. PMID:23263008

  11. Growth signaling promotes chronological aging in budding yeast by inducing superoxide anions that inhibit quiescence

    PubMed Central

    Weinberger, Martin; Mesquita, Ana; Carroll, Timothy; Marks, Laura; Yang, Hui; Zhang, Zhaojie; Ludovico, Paula; Burhans, William C.

    2010-01-01

    Inhibition of growth signaling pathways protects against aging and age-related diseases in parallel with reduced oxidative stress. The relationships between growth signaling, oxidative stress and aging remain unclear. Here we report that in Saccharomyces cerevisiae, alterations in growth signaling pathways impact levels of superoxide anions that promote chronological aging and inhibit growth arrest of stationary phase cells in G0/G1. Factors that decrease intracellular superoxide anions in parallel with enhanced longevity and more efficient G0/G1 arrest include genetic inactivation of growth signaling pathways that inhibit Rim15p, which activates oxidative stress responses, and downregulation of these pathways by caloric restriction. Caloric restriction also reduces superoxide anions independently of Rim15p by elevating levels of H2O2, which activates superoxide dismutases. In contrast, high glucose or mutations that activate growth signaling accelerate chronological aging in parallel with increased superoxide anions and reduced efficiency of stationary phase G0/G1 arrest. High glucose also activates DNA damage responses and preferentially kills stationary phase cells that fail to arrest growth in G0/G1. These findings suggest that growth signaling promotes chronological aging in budding yeast by elevating superoxide anions that inhibit quiescence and induce DNA replication stress. A similar mechanism likely contributes to aging and age-related diseases in complex eukaryotes. PMID:21076178

  12. THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN

    EPA Science Inventory

    THE INFLUENCE OF MAGNETIC FIELDS ON INHIBITION OF MCF-7 CELL GROWTH BY TAMOXIFEN.
    Harland and Liburdy (1) reported that 1.2-uT, 60-Hz magnetic fields could significantly block the inhibitory action of pharmacological levels of tamoxifen (10-7 M) on the growth of MCF-7 human br...

  13. Serotypes of Plasmodium falciparum defined by immune serum inhibition of in vitro growth*

    PubMed Central

    Chulay, J. D.; Haynes, J. D.; Diggs, C. L.

    1985-01-01

    In vitro growth inhibition assays were used to detect antigenic differences among geographically distinct strains of Plasmodium falciparum. Owl monkeys were immunized against the Camp and FCR-3/FMG strains of P. falciparum by infection, drug treatment, and rechallenge with homologous parasites. Camp-immune monkey serum was used to inhibit the in vitro growth of eight strains of P. falciparum. Inhibition was maximum for the homologous Camp strain (an average of 62% inhibition by 100 ml/litre Camp-immune serum). Four other strains were inhibited to a lesser degree, and three strains (FCR-3/FMG, FVO, and Smith) were not significantly inhibited by Camp-immune serum at concentrations as high as 400 ml/litre. FCR-3/FMG-immune serum at a concentration of 50 ml/litre caused significant inhibition of the FCR-3/FMG strain, but not the Camp strain. Thus Camp and FCR-3/FMG strains appear to bear distinct antigenic determinants recognized by the homologous, but not the heterologous, antiserum. Inhibition of in vitro growth by immune serum may be useful for serotyping P. falciparum and may have application in the selection of strains for inclusion in a malaria vaccine. PMID:3893775

  14. In vitro growth inhibition of mastitis pathogens by bovine teat skin normal flora.

    PubMed Central

    Woodward, W D; Besser, T E; Ward, A C; Corbeil, L B

    1987-01-01

    One factor contributing to differences in the susceptibility of cows to mastitis may be differences in the teat skin normal flora, which could inhibit or enhance the growth of pathogenic bacteria. Using in vitro cross-streaking methods, we found that 25% of the isolates of teat normal flora of non-lactating heifers inhibited the growth of selected mastitis pathogens, but enhancers were not detected. Gram-positive pathogens were inhibited to a greater extent than Gram-negative pathogens. Inhibition was not a characteristic of specific genera or species of normal flora, but rather a property of certain variants within a species. This phenomenon of inhibition of mastitis pathogens in vitro by normal flora may be useful as an in vivo biological control method to reduce the incidence of mastitis. PMID:3552170

  15. Decreased abundance of crustose coralline algae due to ocean acidification

    USGS Publications Warehouse

    Kuffner, Ilsa B.; Andersson, Andreas J; Jokiel, Paul L.; Rodgers, Ku'ulei S.; Mackenzie, Fred T.

    2008-01-01

    Owing to anthropogenic emissions, atmospheric concentrations of carbon dioxide could almost double between 2006 and 2100 according to business-as-usual carbon dioxide emission scenarios1. Because the ocean absorbs carbon dioxide from the atmosphere2, 3, 4, increasing atmospheric carbon dioxide concentrations will lead to increasing dissolved inorganic carbon and carbon dioxide in surface ocean waters, and hence acidification and lower carbonate saturation states2, 5. As a consequence, it has been suggested that marine calcifying organisms, for example corals, coralline algae, molluscs and foraminifera, will have difficulties producing their skeletons and shells at current rates6, 7, with potentially severe implications for marine ecosystems, including coral reefs6, 8, 9, 10, 11. Here we report a seven-week experiment exploring the effects of ocean acidification on crustose coralline algae, a cosmopolitan group of calcifying algae that is ecologically important in most shallow-water habitats12, 13, 14. Six outdoor mesocosms were continuously supplied with sea water from the adjacent reef and manipulated to simulate conditions of either ambient or elevated seawater carbon dioxide concentrations. The recruitment rate and growth of crustose coralline algae were severely inhibited in the elevated carbon dioxide mesocosms. Our findings suggest that ocean acidification due to human activities could cause significant change to benthic community structure in shallow-warm-water carbonate ecosystems.

  16. Inhibition of the growth of Lewis lung carcinoma by indomethacin in conventional, nude, and beige mice.

    PubMed

    Maca, R D

    1988-12-01

    The effects of a prostaglandin synthesis inhibitor, indomethacin (Indo), on the growth of Lewis lung carcinoma (LLC) growing as primary subcutaneous tumors in either conventional C57BL/6 mice, T cell deficient nude mice, or natural killer (NK) cell deficient beige mice were studied. In conventional mice, Indo, when continuously administered in the drinking water, consistently and significantly inhibited, in a dose-related fashion, the growth of LLC implanted either subcutaneously in the footpad or in the inguinal region; however, the degree of inhibition of footpad tumor appeared to be greater than that of inguinal tumor. Maximum inhibition was found when Indo was initiated before detectable or measurable tumor developed. If Indo treatment was initiated after tumor growth was evident, then Indo was found to be less effective, although significant inhibition was still observed. Indo also effectively inhibited LLC growing either in the footpad or in the inguinal region of nude or beige mice. The degree of inhibition of both footpad and inguinal tumors in both these mice was comparable to that seen in conventional C57BL/6 mice, indicating that mature T cells, NK cells, or soluble products produced only by these cells are not involved in mediating or modulating the inhibitory effects of Indo on LLC growth. Although Indo treatment significantly inhibited LLC growth in vivo, continuous treatment of cultured LLC cells with Indo in vitro did not decrease the growth of cultured cells. These results indicate that the inhibitory effect of Indo in vivo is not the result of a direct inhibitory effect of Indo on these tumor cells. Lastly, this inhibitory effect of Indo in vivo could not be reversed or negated, not even in part, by the simultaneous, daily i.p. administration of 16,16-dimethyl-PGE2. This finding suggests that the inhibitory effect of Indo involves a mechanism other than the inhibition of prostaglandin E2 production. PMID:3216222

  17. The effect of various carbon sources on the growth of single-celled cyanophyta

    NASA Technical Reports Server (NTRS)

    Avilov, I. A.; Sidorenkova, E. S.

    1983-01-01

    In 19 strains of unicellular blue-green algae, belonging to general Synechococcus, Synechocystis, Aphanocapsa and Aphanothece, the capacity of growth under mixotrophic conditions in mineral media with organic carbon sources (carbohydrates, polyols) was investigated. At moderate light intensity (1200 lx) and 0.5% of carbon source there was revealed: (1) Stimulation of growth; (2) Partial or complete inhibition of growth; (3) No influence of carbohydrate and polyols on the growth of some algae strains. Three physiological groups for the investigated strains have been outlined on the basis of data obtained. The possibility of using the differences revealed in classification of unicellular blue-green algae is discussed.

  18. IN VITRO INHIBITION OF YEAST GROWTH BY MOUSE ASCITES FLUID AND SERUM.

    PubMed

    SUMMERS, D F; HASENCLEVER, H F

    1964-01-01

    Summers, Donald F. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), and H. F. Hasenclever. In vitro inhibition of yeast growth by mouse ascites fluid and serum. J. Bacteriol. 87:1-7. 1964.-A nondialyzable heat-stable factor(s) present in experimentally produced mouse ascites fluid and in serum from these ascitic mice was shown to inhibit the invitro growth of several yeasts. The inhibitory activity was almost totally abolished by trypsin treatment of the ascites fluid, and was progressively diminished by repeated adsorption of the ascites fluid by heat-killed Candida albicans cells. A close relationship was shown to exist between growth inhibition by ascites fluid and concentration of free iron or nutrients in the growth medium. Increased concentration of nutrients or free iron caused diminution of inhibitory activity. PMID:14102855

  19. IN VITRO INHIBITION OF YEAST GROWTH BY MOUSE ASCITES FLUID AND SERUM

    PubMed Central

    Summers, Donald F.; Hasenclever, H. F.

    1964-01-01

    Summers, Donald F. (National Institute of Allergy and Infectious Diseases, Bethesda, Md.), and H. F. Hasenclever. In vitro inhibition of yeast growth by mouse ascites fluid and serum. J. Bacteriol. 87:1–7. 1964.—A nondialyzable heat-stable factor(s) present in experimentally produced mouse ascites fluid and in serum from these ascitic mice was shown to inhibit the invitro growth of several yeasts. The inhibitory activity was almost totally abolished by trypsin treatment of the ascites fluid, and was progressively diminished by repeated adsorption of the ascites fluid by heat-killed Candida albicans cells. A close relationship was shown to exist between growth inhibition by ascites fluid and concentration of free iron or nutrients in the growth medium. Increased concentration of nutrients or free iron caused diminution of inhibitory activity. PMID:14102855

  20. Verbascoside Inhibits Promastigote Growth and Arginase Activity of Leishmania amazonensis.

    PubMed

    Maquiaveli, Claudia C; Lucon-Júnior, João F; Brogi, Simone; Campiani, Giuseppe; Gemma, Sandra; Vieira, Paulo C; Silva, Edson R

    2016-05-27

    Verbascoside (1) is a phenylethanoid glycoside that has antileishmanial activity against Leishmania infantum and Leishmania donovani. In this study, we verified the activity of 1 on Leishmania amazonensis and arginase inhibition. Compound 1 showed an EC50 of 19 μM against L. amazonensis promastigotes and is a competitive arginase inhibitor (Ki = 0.7 μM). Docking studies were performed to assess the interaction of 1 with arginase at the molecular level. Arginase is an enzyme of the polyamine biosynthesis pathway that is important to parasite infectivity, and the results of our study suggest that 1 could be useful to develop new approaches for treating leishmaniasis. PMID:27096224

  1. Neuropeptide Y inhibits cholangiocarcinoma cell growth and invasion

    PubMed Central

    DeMorrow, Sharon; Onori, Paolo; Venter, Julie; Invernizzi, Pietro; Frampton, Gabriel; White, Mellanie; Franchitto, Antonio; Kopriva, Shelley; Bernuzzi, Francesca; Francis, Heather; Coufal, Monique; Glaser, Shannon; Fava, Giammarco; Meng, Fanyin; Alvaro, Domenico; Carpino, Guido; Gaudio, Eugenio

    2011-01-01

    No information exists on the role of neuropeptide Y (NPY) in cholangiocarcinoma growth. Therefore, we evaluated the expression and secretion of NPY and its subsequent effects on cholangiocarcinoma growth and invasion. Cholangiocarcinoma cell lines and nonmalignant cholangiocytes were used to assess NPY mRNA expression and protein secretion. NPY expression was assessed by immunohistochemistry in human liver biopsies. Cell proliferation and migration were evaluated in vitro by MTS assays and matrigel invasion chambers, respectively, after treatment with NPY or a neutralizing NPY antibody. The effect of NPY or NPY depletion on tumor growth was assessed in vivo after treatment with NPY or the neutralizing NPY antibody in a xenograft model of cholangiocarcinoma. NPY secretion was upregulated in cholangiocarcinoma compared with normal cholangiocytes. Administration of exogenous NPY decreased proliferation and cell invasion in all cholangiocarcinoma cell lines studied and reduced tumor cell growth in vivo. In vitro, the effects of NPY on proliferation were blocked by specific inhibitors for NPY receptor Y2, but not Y1 or Y5, and were associated with an increase in intracellular d-myo-inositol 1,4,5-trisphosphate and PKCα activation. Blocking of NPY activity using a neutralizing antibody promoted cholangiocarcinoma growth in vitro and in vivo and increased the invasiveness of cholangiocarcinoma in vitro. Increased NPY immunoreactivity in human tumor tissue occurred predominantly in the center of the tumor, with less expression toward the invasion front of the tumor. We demonstrated that NPY expression is upregulated in cholangiocarcinoma, which exerts local control on tumor cell proliferation and invasion. Modulation of NPY secretion may be important for the management of cholangiocarcinoma. PMID:21270292

  2. Breakdown of the coral-algae symbiosis: towards formalising a linkage between warm-water bleaching thresholds and the growth rate of the intracellular zooxanthellae

    NASA Astrophysics Data System (ADS)

    Wooldridge, S. A.

    2012-07-01

    Impairment of the photosynthetic machinery of the algal endosymbiont ("zooxanthellae") is the proximal trigger for the thermal breakdown of the coral-algae symbiosis ("coral bleaching"). Yet, the primary site of thermal damage is not well resolved. In this perspective essay, I consider further a recent hypothesis which proposes an energetic disruption to the carbon-concentrating mechanisms (CCMs) of the coral host, and the resultant onset of CO2-limitation within the photosynthetic "dark reactions", as a unifying cellular mechanism. The hypothesis identifies the enhanced retention of photosynthetic carbon for zooxanthellae (re)growth following an initial irradiance-driven expulsion event as the cause of the energetic disruption. If true, then it implies that the onset of the bleaching syndrome and setting of upper thermal bleaching limits are emergent attributes of the coral symbiosis that are ultimately underpinned by the characteristic growth profile of the intracellular zooxanthellae; which is known to depend not just on temperature, but also external (seawater) nutrient availability and zooxanthellae genotype. Here, I review this proposed bleaching linkage at a variety of observational scales, and find it to be parsimonious with the available evidence. This provides a new standpoint to consider the future prospects of the coral symbiosis in an era of rapid environmental change, including the now crucial importance of reef water quality in co-determining thermal bleaching resistance.

  3. Tankyrase Inhibitor Sensitizes Lung Cancer Cells to Endothelial Growth Factor Receptor (EGFR) Inhibition via Stabilizing Angiomotins and Inhibiting YAP Signaling.

    PubMed

    Wang, Hui; Lu, Bo; Castillo, Johnny; Zhang, Yue; Yang, Zinger; McAllister, Gregory; Lindeman, Alicia; Reece-Hoyes, John; Tallarico, John; Russ, Carsten; Hoffman, Greg; Xu, Wenqing; Schirle, Markus; Cong, Feng

    2016-07-15

    YAP signaling pathway plays critical roles in tissue homeostasis, and aberrant activation of YAP signaling has been implicated in cancers. To identify tractable targets of YAP pathway, we have performed a pathway-based pooled CRISPR screen and identified tankyrase and its associated E3 ligase RNF146 as positive regulators of YAP signaling. Genetic ablation or pharmacological inhibition of tankyrase prominently suppresses YAP activity and YAP target gene expression. Using a proteomic approach, we have identified angiomotin family proteins, which are known negative regulators of YAP signaling, as novel tankyrase substrates. Inhibition of tankyrase or depletion of RNF146 stabilizes angiomotins. Angiomotins physically interact with tankyrase through a highly conserved motif at their N terminus, and mutation of this motif leads to their stabilization. Tankyrase inhibitor-induced stabilization of angiomotins reduces YAP nuclear translocation and decreases downstream YAP signaling. We have further shown that knock-out of YAP sensitizes non-small cell lung cancer to EGFR inhibitor Erlotinib. Tankyrase inhibitor, but not porcupine inhibitor, which blocks Wnt secretion, enhances growth inhibitory activity of Erlotinib. This activity is mediated by YAP inhibition and not Wnt/β-catenin inhibition. Our data suggest that tankyrase inhibition could serve as a novel strategy to suppress YAP signaling for combinatorial targeted therapy. PMID:27231341

  4. DSGOST inhibits tumor growth by blocking VEGF/VEGFR2-activated angiogenesis

    PubMed Central

    Choi, Hyeong Sim; Lee, Kangwook; Kim, Min Kyoung; Lee, Kang Min; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

    2016-01-01

    Tumor growth requires a process called angiogenesis, a new blood vessel formation from pre-existing vessels, as newly formed vessels provide tumor cells with oxygen and nutrition. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST), one of traditional Chinese medicines, has been widely used in treatment of vessel diseases including Raynaud's syndrome in Northeast Asian countries including China, Japan and Korea. Therefore, we hypothesized that DSGOST might inhibit tumor growth by targeting newly formed vessels on the basis of its historical prescription. Here, we demonstrate that DSGOST inhibits tumor growth by inhibiting VEGF-induced angiogenesis. DSGOST inhibited VEGF-induced angiogenic abilities of endothelial cells in vitro and in vivo, which resulted from its inhibition of VEGF/VEGFR2 interaction. Furthermore, DSGOST attenuated pancreatic tumor growth in vivo by reducing angiogenic vessel numbers, while not affecting pancreatic tumor cell viability. Thus, our data conclude that DSGOST inhibits VEGF-induced tumor angiogenesis, suggesting a new indication for DSGOST in treatment of cancer. PMID:26967562

  5. Inhibition of breast cancer growth and metastasis by a biomimetic peptide

    PubMed Central

    Lee, Esak; Lee, Seung Jae; Koskimaki, Jacob E.; Han, Zheyi; Pandey, Niranjan B.; Popel, Aleksander S.

    2014-01-01

    Metastasis is the main cause of mortality in cancer patients. Though there are many anti-cancer drugs targeting primary tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression, particularly, lymphangiogenesis is pivotal for metastasis in breast cancer. Here we report that a novel collagen IV derived biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis. The peptide inhibits blood and lymphatic endothelial cell viability, migration, adhesion, and tube formation by targeting IGF1R and Met signals. The peptide blocks MDA-MB-231 tumor growth by inhibiting tumor angiogenesis in vivo. Moreover, the peptide inhibits lymphangiogenesis in primary tumors. MDA-MB-231 tumor conditioned media (TCM) was employed to accelerate spontaneous metastasis in tumor xenografts, and the anti-metastatic activity of the peptide was tested in this model. The peptide prevents metastasis to the lungs and lymph nodes by inhibiting TCM-induced lymphangiogenesis and angiogenesis in the pre-metastatic organs. In summary, a novel biomimetic peptide inhibits breast cancer growth and metastasis by blocking angiogenesis and lymphangiogenesis in the pre-metastatic organs as well as primary tumors. PMID:25409905

  6. Transcription factor LSF (TFCP2) inhibits melanoma growth

    PubMed Central

    Goto, Yuji; Yajima, Ichiro; Kumasaka, Mayuko; Ohgami, Nobutaka; Tanaka, Asami; Tsuzuki, Toyonori; Inoue, Yuji; Fukushima, Satoshi; Ihn, Hironobu; Kyoya, Mikiko; Ohashi, Hiroyuki; Kawakami, Tamihiro; Bennett, Dorothy C.; Kato, Masashi

    2016-01-01

    Late SV40 factor 3 (LSF), a transcription factor, contributes to human hepatocellular carcinoma (HCC). However, decreased expression level of LSF in skin melanoma compared to that in benign melanocytic tumors and nevi in mice and humans was found in this study. Anchorage-dependent and -independent growth of melanoma cells was suppressed by LSF overexpression through an increased percentage of G1 phase cells and an increased p21CIP1 expression level in vitro and in vivo. Anchorage-dependent growth in LSF-overexpressed melanoma cells was promoted by depletion of LSF in the LSF-overexpressed cells. Integrated results of our EMSA and chromatin immunoprecipitation assays showed binding of LSF within a 150-bp upstream region of the transcription start site of p21CIP1 in melanoma cells. Taken together, our results suggest potential roles of LSF as a growth regulator through control of the transcription of p21CIP1 in melanocytes and melanoma cells as well as a biomarker for nevus. PMID:26506241

  7. Transcription factor LSF (TFCP2) inhibits melanoma growth.

    PubMed

    Goto, Yuji; Yajima, Ichiro; Kumasaka, Mayuko; Ohgami, Nobutaka; Tanaka, Asami; Tsuzuki, Toyonori; Inoue, Yuji; Fukushima, Satoshi; Ihn, Hironobu; Kyoya, Mikiko; Ohashi, Hiroyuki; Kawakami, Tamihiro; Bennett, Dorothy C; Kato, Masashi

    2016-01-19

    Late SV40 factor 3 (LSF), a transcription factor, contributes to human hepatocellular carcinoma (HCC). However, decreased expression level of LSF in skin melanoma compared to that in benign melanocytic tumors and nevi in mice and humans was found in this study. Anchorage-dependent and -independent growth of melanoma cells was suppressed by LSF overexpression through an increased percentage of G1 phase cells and an increased p21CIP1 expression level in vitro and in vivo. Anchorage-dependent growth in LSF-overexpressed melanoma cells was promoted by depletion of LSF in the LSF-overexpressed cells. Integrated results of our EMSA and chromatin immunoprecipitation assays showed binding of LSF within a 150-bp upstream region of the transcription start site of p21CIP1 in melanoma cells. Taken together, our results suggest potential roles of LSF as a growth regulator through control of the transcription of p21CIP1 in melanocytes and melanoma cells as well as a biomarker for nevus. PMID:26506241

  8. Leaf Litter Inhibits Growth of an Amphibian Fungal Pathogen.

    PubMed

    Stoler, Aaron B; Berven, Keith A; Raffel, Thomas R

    2016-06-01

    Past studies have found a heterogeneous distribution of the amphibian chytrid fungal pathogen, Batrachochytrium dendrobatidis (Bd). Recent studies have accounted for some of this heterogeneity through a positive association between canopy cover and Bd abundance, which is attributed to the cooling effect of canopy cover. We questioned whether leaf litter inputs that are also associated with canopy cover might also alter Bd growth. Leaf litter inputs exhibit tremendous interspecific chemical variation, and we hypothesized that Bd growth varies with leachate chemistry. We also hypothesized that Bd uses leaf litter as a growth substrate. To test these hypotheses, we conducted laboratory trials in which we exposed cultures of Bd to leachate of 12 temperate leaf litter species at varying dilutions. Using a subset of those 12 litter species, we also exposed Bd to pre-leached litter substrate. We found that exposure to litter leachate and substrate reduced Bd spore and sporangia densities, although there was substantial variation among treatments. In particular, Bd densities were inversely correlated with concentrations of phenolic acids. We conducted a field survey of phenolic concentrations in natural wetlands which verified that the leachate concentrations in our lab study are ecologically relevant. Our study reinforces prior indications that positive associations between canopy cover and Bd abundance are likely mediated by water temperature effects, but this phenomenon might be counteracted by changes in aquatic chemistry from leaf litter inputs. PMID:26935822

  9. Role of calcium in growth inhibition induced by a novel cell surface sialoglycopeptide

    NASA Technical Reports Server (NTRS)

    Betz, N. A.; Westhoff, B. A.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Our laboratory has purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) from intact bovine cerebral cortex cells. Evidence presented here demonstrates that sensitivity to CeReS-18-induced growth inhibition in BALB-c 3T3 cells is influenced by calcium, such that a decrease in the calcium concentration in the growth medium results in an increase in sensitivity to CeReS-18. Calcium did not alter CeReS-18 binding to its cell surface receptor and CeReS-18 does not bind calcium directly. Addition of calcium, but not magnesium, to CeReS-18-inhibited 3T3 cells results in reentry into the cell cycle. A greater than 3-hour exposure to increased calcium is required for escape from CeReS-18-induced growth inhibition. The calcium ionophore ionomycin could partially mimic the effect of increasing extracellular calcium, but thapsigargin was ineffective in inducing escape from growth inhibition. Increasing extracellular calcium 10-fold resulted in an approximately 7-fold increase in total cell-associated 45Ca+2, while free intracellular calcium only increased approximately 30%. However, addition of CeReS-18 did not affect total cell-associated calcium or the increase in total cell-associated calcium observed with an increase in extracellular calcium. Serum addition induced mobilization of intracellular calcium and influx across the plasma membrane in 3T3 cells, and pretreatment of 3T3 cells with CeReS-18 appeared to inhibit these calcium mobilization events. These results suggest that a calcium-sensitive step exists in the recovery from CeReS-18-induced growth inhibition. CeReS-18 may inhibit cell proliferation through a novel mechanism involving altering the intracellular calcium mobilization/regulation necessary for cell cycle progression.

  10. Sumoylation Inhibits the Growth Suppressive Properties of Ikaros

    PubMed Central

    Goepp, Marie; Kirstetter, Peggy; Marchal, Patricia; Ittel, Antoine; Mauvieux, Laurent; Chan, Susan; Kastner, Philippe

    2016-01-01

    The Ikaros transcription factor is a tumor suppressor that is also important for lymphocyte development. How post-translational modifications influence Ikaros function remains partially understood. We show that Ikaros undergoes sumoylation in developing T cells that correspond to mono-, bi- or poly-sumoylation by SUMO1 and/or SUMO2/3 on three lysine residues (K58, K240 and K425). Sumoylation occurs in the nucleus and requires DNA binding by Ikaros. Sumoylated Ikaros is less effective than unsumoylated forms at inhibiting the expansion of murine leukemic cells, and Ikaros sumoylation is abundant in human B-cell acute lymphoblastic leukemic cells, but not in healthy peripheral blood leukocytes. Our results suggest that sumoylation may be important in modulating the tumor suppressor function of Ikaros. PMID:27315244

  11. Somatostatin receptor-1 induces cell cycle arrest and inhibits tumor growth in pancreatic cancer.

    PubMed

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E

    2008-11-01

    Functional somatostatin receptors (SSTR) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G(0)/G(1) growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n = 5, P < 0.05, Student's t-test), and inhibited tumor weight by 69% and 47% (n = 5, P < 0.05, Student's t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376

  12. Somatostatin Receptor-1 Induces Cell Cycle Arrest and Inhibits Tumor Growth in Pancreatic Cancer

    PubMed Central

    Li, Min; Wang, Xiaochi; Li, Wei; Li, Fei; Yang, Hui; Wang, Hao; Brunicardi, F. Charles; Chen, Changyi; Yao, Qizhi; Fisher, William E.

    2010-01-01

    Functional somatostatin receptors (SSTRs) are lost in human pancreatic cancer. Transfection of SSTR-1 inhibited pancreatic cancer cell proliferation in vitro. We hypothesize that stable transfection of SSTR-1 may inhibit pancreatic cancer growth in vivo possibly through cell cycle arrest. In this study, we examined the expression of SSTR-1 mRNA in human pancreatic cancer tissue specimens, and investigated the effect of SSTR-1 overexpression on cell proliferation, cell cycle, and tumor growth in in a subcutaneous nude mouse model. We found that SSTR-1 mRNA was downregulated in the majority of pancreatic cancer tissue specimens. Transfection of SSTR-1 caused cell cycle arrest at the G0/G1 growth phase, with a corresponding decline of cells in the S (mitotic) phase. The overexpression of SSTR-1 significantly inhibited subcutaneous tumor size by 71% and 43% (n=5, p<0.05, t-test), and inhibited tumor weight by 69% and 47%, (n=5, p<0.05, t-test), in Panc-SSTR-1 and MIA-SSTR-1 groups, respectively, indicating the potent inhibitory effect of SSTR-1 on pancreatic cancer growth. Our data demonstrate that overexpression of SSTR-1 significantly inhibits pancreatic cancer growth possibly through cell cycle arrest. This study suggests that gene therapy with SSTR-1 may be a potential adjuvant treatment for pancreatic cancer. PMID:18823376

  13. Bisphenol A inhibits cultured mouse ovarian follicle growth partially via the aryl hydrocarbon receptor signaling pathway

    PubMed Central

    Ziv-Gal, Ayelet; Craig, Zelieann R.; Wang, Wei; Flaws, Jodi A.

    2013-01-01

    Bisphenol A (BPA) is an endocrine disruptor that inhibits growth of mouse ovarian follicles and disrupts steroidogenesis at a dose of 438 μM. However, the effects of lower doses of BPA and its mechanism of action in ovarian follicles are unknown. We hypothesized that low doses of BPA inhibit follicular growth and decrease estradiol levels through the aryl hydrocarbon receptor (AHR) pathway. Antral follicles from wild-type and Ahr knock-out (AhrKO) mice were cultured for 96 hours. Follicle diameters and estradiol levels then were compared in wild-type and AhrKO follicles ± BPA (0.004 - 438 μM). BPA inhibited follicle growth (110 - 438 μM) and decreased estradiol levels (43.8 - 438 μM) in wild-type and AhrKO follicles. However, at BPA 110 μM, inhibition of growth in AhrKO follicles was attenuated compared to wild-type follicles. These data suggest that BPA may inhibit follicle growth partially via the AHR pathway, whereas its effects on estradiol synthesis likely involve other mechanisms. PMID:23928317

  14. Antizyme induction by polyamine analogues as a factor of cell growth inhibition.

    PubMed Central

    Mitchell, John L A; Leyser, Aviva; Holtorff, Michelle S; Bates, Jill S; Frydman, Benjamin; Valasinas, Aldonia L; Reddy, Venodhar K; Marton, Laurence J

    2002-01-01

    The polyamines spermidine and spermine and their diamine precursor putrescine are essential for mammalian cell growth and viability, and strategies are sought for reducing polyamine levels in order to inhibit cancer growth. Several structural analogues of the polyamines have been found to decrease natural polyamine levels and inhibit cell growth, probably by stimulating normal feedback mechanisms. In the present study, a large selection of spermine analogues has been tested for their effectiveness in inducing the production of antizyme, a key protein in feedback inhibition of putrescine synthesis and cellular polyamine uptake. Bisethylnorspermine, bisethylhomospermine, 1,19-bis-(ethylamino)-5,10,15-triazanonadecane, longer oligoamine constructs and many conformationally constrained analogues of these compounds were found to stimulate antizyme synthesis to different levels in rat liver HTC cells, with some producing far more antizyme than the natural polyamine spermine. Uptake of the tested compounds was found to be dependent on, and limited by, the polyamine transport system, for which all these have approximately equal affinity. These analogues differed in their ability to inhibit HTC cell growth during 3 days of exposure, and this ability correlated with their antizyme-inducing potential. This is the first direct evidence that antizyme is induced by several polyamine analogues. Selection of analogues with this potential may be an effective strategy for maximizing polyamine deprivation and growth inhibition. PMID:11972449

  15. Inhibition of cell growth by a hypothalamic peptide.

    PubMed Central

    Redding, T W; Schally, A V

    1982-01-01

    A fraction purified from acetic acid extracts of porcine hypothalami was found to contain significant antimitogenic activity when tested in normal and neoplastic cell lines. Addition of this hypothalamic material (1-100 micrograms/ml) to culture media significantly inhibited [3H]thymidine incorporation into cellular DNA in several cell lines. Amino acid incorporation into pituitary proteins and uridine incorporation into RNA were also significantly reduced by this factor(s). Addition to the culture media of this hypothalamic material at 5 micrograms/ml and 50 micrograms/ml per day decreased by 17% and 36%, respectively, cell numbers of 3T6 fibroblast cell cultures. Time-response curves showed that the inhibition of [3H]thymidine incorporation into DNA in 3T6 fibroblast cells begins within 2 hr after adding this fraction to the culture medium. The inhibitory action cannot be explained by a direct cytotoxic effect since 3T6 cells labeled with 51Cr and incubated for 6 hr in the presence of this hypothalamic fraction fail to show an increase in the release of 51Cr into the medium as compared with controls. Incubation with trypsin and chymotrypsin completely abolished the antimitogenic activity of this material and pepsin decreased it. This strongly suggests that the antimitogenic activity exhibited by this fraction is due to a polypeptide(s). These observations provide evidence for the presence in the mammalian hypothalamus of an antimitogenic peptide(s) that may be involved in the regulation of cell proliferation. PMID:6757925

  16. Specific Bifidobacterium strains isolated from elderly subjects inhibit growth of Staphylococcus aureus.

    PubMed

    Lahtinen, Sampo J; Jalonen, Lotta; Ouwehand, Arthur C; Salminen, Seppo J

    2007-06-10

    Cell-free, pH-controlled supernatants of thirty-eight Bifidobacterium strains isolated from healthy elderly subjects were subjected to antimicrobial activity assay. Bioluminescent indicator strains Staphylococcus aureus RN4220, Escherichia coli K-12, and Salmonella enterica serovar Typhimurium ATCC 14028 were used as targets of antimicrobial activity. The effect of nutrient depletion on the inhibition was eliminated with spent-culture controls. Three out of thirty-eight Bifidobacterium strains were capable of inhibiting the growth of S. aureus. The inhibition was equal to 23.2+/-19.1% to 50.4+/-26.7% of the inhibition caused by 50 IU/ml nisin. Reuterin-producing positive strain Lactobacillus reuteri SD2112 was capable of 86.0+/-24.6% inhibition, but Bifidobacterium lactis Bb-12, a known probiotic strain, showed no inhibition. None of the strains was capable of inhibiting the growth of E. coli or S. enterica. The observed inhibition by bifidobacteria was related to hydrogen peroxide formation and possible production of heat-stable proteinaceous compounds. The results suggest that production of antimicrobial substances other than organic acids is not common among Bifidobacterium strains typical of elderly subjects. However, specific strains were identified which showed considerable inhibitory activity against S. aureus. PMID:17462772

  17. Vitamin K enhancement of Sorafenib-mediated HCC cell growth inhibition in vitro and in vivo

    PubMed Central

    Wei, Gang; Wang, Meifanf; Hyslop, Terry; Wang, Ziqiu; Carr, Brian I.

    2010-01-01

    The multi-kinase inhibitor Sorafenib, is the first oral agent to show activity against human hepatocellular carcinoma (HCC). Apoptosis has been shown to be induced in HCC by several agents, including Sorafenib, as well as by the naturally occurring K vitamins (VKs). Since few non toxic agents have activity against HCC growth, we evaluated the activity of Sorafenib and K vitamins, both independently and together on the growth in vitro and in vivo of HCC cells. We found that when VK was combined with Sorafenib, the concentration of Sorafenib required for growth inhibition was substantially reduced. Conversely, VK enhanced Sorafenib effects in several HCC cell lines on growth inhibition. Growth could be inhibited at doses of VK plus Sorafenib that were ineffective with either agent alone,using vitamins K1, K2 and K5. Combination VK1 plus Sorafenib induced apoptosis on FACS, TUNEL staining and caspase activation. Phospho-ERK levels were decreased, as was Mcl-1, an ERK target. Sorafenib alone inhibited growth of transplantable HCC in vivo. At sub-effective Sorafenib doses in vivo, addition of VK1 caused major tumor regression, with decreased phospho-ERK and Mcl-1 staining. Thus, combination VK1 plus Sorafenib strongly induced growth inhibition and apoptosis in rodent and human HCC and inhibited the RAF/MEK/ERK pathway. VK1 alone activated PKA, a mediator of inhibitory Raf phosphorylation. Thus, each agent can antagonize Raf; Sorafenib as a direct inhibitor and VK1 through inhibitory Raf phosphorylation. Since both agents are available for human use, the combination has potential for improving Sorafenib effects in HCC. PMID:21351273

  18. Prolyl oligopeptidase inhibition-induced growth arrest of human gastric cancer cells

    SciTech Connect

    Suzuki, Kanayo; Sakaguchi, Minoru; Tanaka, Satoshi; Yoshimoto, Tadashi; Takaoka, Masanori

    2014-01-03

    Highlights: •We examined the effects of prolyl oligopeptidase (POP) inhibition on p53 null gastric cancer cell growth. •POP inhibition-induced cell growth suppression was associated with an increase in a quiescent G{sub 0} state. •POP might regulate the exit from and/or reentry into the cell cycle. -- Abstract: Prolyl oligopeptidase (POP) is a serine endopeptidase that hydrolyzes post-proline peptide bonds in peptides that are <30 amino acids in length. We recently reported that POP inhibition suppressed the growth of human neuroblastoma cells. The growth suppression was associated with pronounced G{sub 0}/G{sub 1} cell cycle arrest and increased levels of the CDK inhibitor p27{sup kip1} and the tumor suppressor p53. In this study, we investigated the mechanism of POP inhibition-induced cell growth arrest using a human gastric cancer cell line, KATO III cells, which had a p53 gene deletion. POP specific inhibitors, 3-((4-[2-(E)-styrylphenoxy]butanoyl)-L-4-hydroxyprolyl)-thiazolidine (SUAM-14746) and benzyloxycarbonyl-thioprolyl-thioprolinal, or RNAi-mediated POP knockdown inhibited the growth of KATO III cells irrespective of their p53 status. SUAM-14746-induced growth inhibition was associated with G{sub 0}/G{sub 1} cell cycle phase arrest and increased levels of p27{sup kip1} in the nuclei and the pRb2/p130 protein expression. Moreover, SUAM-14746-mediated cell cycle arrest of KATO III cells was associated with an increase in the quiescent G{sub 0} state, defined by low level staining for the proliferation marker, Ki-67. These results indicate that POP may be a positive regulator of cell cycle progression by regulating the exit from and/or reentry into the cell cycle by KATO III cells.

  19. Algal Feedback and Removal Efficiency in a Sequencing Batch Reactor Algae Process (SBAR) to Treat the Antibiotic Cefradine

    PubMed Central

    Chen, Jianqiu; Zheng, Fengzhu; Guo, Ruixin

    2015-01-01

    Many previous studies focused on the removal capability for contaminants when the algae grown in an unexposed, unpolluted environment and ignored whether the feedback of algae to the toxic stress influenced the removal capability in a subsequent treatment batch. The present research investigated and compared algal feedback and removal efficiency in a sequencing batch reactor algae process (SBAR) to remove cefradine. Three varied pollution load conditions (10, 30 and 60 mg/L) were considered. Compared with the algal characteristics in the first treatment batch at 10 and 30 mg/L, higher algal growth inhibition rates were observed in the second treatment batch (11.23% to 20.81%). In contrast, algae produced more photosynthetic pigments in response to cefradine in the second treatment batch. A better removal efficiency (76.02%) was obtained during 96 h when the alga treated the antibiotic at 60 mg/L in the first treatment batch and at 30 mg/L in the second treatment batch. Additionally, the removal rate per unit algal density was also improved when the alga treated the antibiotic at 30 or 60 mg/L in the first treatment batch, respectively and at 30 mg/L in the second treatment batch. Our result indicated that the green algae were also able to adapt to varied pollution loads in different treatment batches. PMID:26177093

  20. Algal Feedback and Removal Efficiency in a Sequencing Batch Reactor Algae Process (SBAR) to Treat the Antibiotic Cefradine.

    PubMed

    Chen, Jianqiu; Zheng, Fengzhu; Guo, Ruixin

    2015-01-01

    Many previous studies focused on the removal capability for contaminants when the algae grown in an unexposed, unpolluted environment and ignored whether the feedback of algae to the toxic stress influenced the removal capability in a subsequent treatment batch. The present research investigated and compared algal feedback and removal efficiency in a sequencing batch reactor algae process (SBAR) to remove cefradine. Three varied pollution load conditions (10, 30 and 60 mg/L) were considered. Compared with the algal characteristics in the first treatment batch at 10 and 30 mg/L, higher algal growth inhibition rates were observed in the second treatment batch (11.23% to 20.81%). In contrast, algae produced more photosynthetic pigments in response to cefradine in the second treatment batch. A better removal efficiency (76.02%) was obtained during 96 h when the alga treated the antibiotic at 60 mg/L in the first treatment batch and at 30 mg/L in the second treatment batch. Additionally, the removal rate per unit algal density was also improved when the alga treated the antibiotic at 30 or 60 mg/L in the first treatment batch, respectively and at 30 mg/L in the second treatment batch. Our result indicated that the green algae were also able to adapt to varied pollution loads in different treatment batches. PMID:26177093

  1. Calcium ion involvement in growth inhibition of mechanically stressed soybean (Glycine max) seedlings

    NASA Technical Reports Server (NTRS)

    Jones, R. S.; Mitchell, C. A.

    1989-01-01

    A 40-50% reduction in soybean [Glycine max (L.) Merr. cv. Century 84] hypocotyl elongation occurred 24 h after application of mechanical stress. Exogenous Ca2+ at 10 mM inhibited growth by 28% if applied with the Ca2+ ionophore A23187 to the zone of maximum hypocotyl elongation. La3+ was even more inhibitory than Ca2+, especially above 5 mM. Treatment with ethyleneglycol-bis-(beta-aminoethylether)-N, N, N', N'-tetraacetic acid (EGTA) alone had no effect on growth of non-stressed seedlings at the concentrations used but negated stress-induced growth reduction by 36% at 4 mM when compared to non-treated, stressed controls. Treatment with EDTA was ineffective in negating stress-induced growth inhibition. Calmodulin antagonists calmidazolium, chlorpromazine, and 48/80 also negated stress-induced growth reduction by 23, 50, and 35%, respectively.

  2. SKI knockdown inhibits human melanoma tumor growth in vivo.

    PubMed

    Chen, Dahu; Lin, Qiushi; Box, Neil; Roop, Dennis; Ishii, Shunsuke; Matsuzaki, Koichi; Fan, Tao; Hornyak, Thomas J; Reed, Jon A; Stavnezer, Ed; Timchenko, Nikolai A; Medrano, Estela E

    2009-12-01

    The SKI protein represses the TGF-beta tumor suppressor pathway by associating with the Smad transcription factors. SKI is upregulated in human malignant melanoma tumors in a disease-progression manner and its overexpression promotes proliferation and migration of melanoma cells in vitro. The mechanisms by which SKI antagonizes TGF-beta signaling in vivo have not been fully elucidated. Here we show that human melanoma cells in which endogenous SKI expression was knocked down by RNAi produced minimal orthotopic tumor xenograft nodules that displayed low mitotic rate and prominent apoptosis. These minute tumors exhibited critical signatures of active TGF-beta signaling including high levels of nuclear Smad3 and p21(Waf-1), which are not found in the parental melanomas. To understand how SKI promotes tumor growth we used gain- and loss-of-function approaches and found that simultaneously to blocking the TGF-beta-growth inhibitory pathway, SKI promotes the switch of Smad3 from tumor suppression to oncogenesis by favoring phosphorylations of the Smad3 linker region in melanoma cells but not in normal human melanocytes. In this context, SKI is required for preventing TGF-beta-mediated downregulation of the oncogenic protein c-MYC, and for inducing the plasminogen activator inhibitor-1, a mediator of tumor growth and angiogenesis. Together, the results indicate that SKI exploits multiple regulatory levels of the TGF-beta pathway and its deficiency restores TGF-beta tumor suppressor and apoptotic activities in spite of the likely presence of oncogenic mutations in melanoma tumors. PMID:19845874

  3. Molecular modifiers reveal a mechanism of pathological crystal growth inhibition.

    PubMed

    Chung, Jihae; Granja, Ignacio; Taylor, Michael G; Mpourmpakis, Giannis; Asplin, John R; Rimer, Jeffrey D

    2016-08-25

    Crystalline materials are crucial to the function of living organisms, in the shells of molluscs, the matrix of bone, the teeth of sea urchins, and the exoskeletons of coccoliths. However, pathological biomineralization can be an undesirable crystallization process associated with human diseases. The crystal growth of biogenic, natural and synthetic materials may be regulated by the action of modifiers, most commonly inhibitors, which range from small ions and molecules to large macromolecules. Inhibitors adsorb on crystal surfaces and impede the addition of solute, thereby reducing the rate of growth. Complex inhibitor-crystal interactions in biomineralization are often not well elucidated. Here we show that two molecular inhibitors of calcium oxalate monohydrate crystallization--citrate and hydroxycitrate--exhibit a mechanism that differs from classical theory in that inhibitor adsorption on crystal surfaces induces dissolution of the crystal under specific conditions rather than a reduced rate of crystal growth. This phenomenon occurs even in supersaturated solutions where inhibitor concentration is three orders of magnitude less than that of the solute. The results of bulk crystallization, in situ atomic force microscopy, and density functional theory studies are qualitatively consistent with a hypothesis that inhibitor-crystal interactions impart localized strain to the crystal lattice and that oxalate and calcium ions are released into solution to alleviate this strain. Calcium oxalate monohydrate is the principal component of human kidney stones and citrate is an often-used therapy, but hydroxycitrate is not. For hydroxycitrate to function as a kidney stone treatment, it must be excreted in urine. We report that hydroxycitrate ingested by non-stone-forming humans at an often-recommended dose leads to substantial urinary excretion. In vitro assays using human urine reveal that the molecular modifier hydroxycitrate is as effective an inhibitor of nucleation of

  4. Hydroxyapatite-binding peptides for bone growth and inhibition

    DOEpatents

    Bertozzi, Carolyn R.; Song, Jie; Lee, Seung-Wuk

    2011-09-20

    Hydroxyapatite (HA)-binding peptides are selected using combinatorial phage library display. Pseudo-repetitive consensus amino acid sequences possessing periodic hydroxyl side chains in every two or three amino acid sequences are obtained. These sequences resemble the (Gly-Pro-Hyp).sub.x repeat of human type I collagen, a major component of extracellular matrices of natural bone. A consistent presence of basic amino acid residues is also observed. The peptides are synthesized by the solid-phase synthetic method and then used for template-driven HA-mineralization. Microscopy reveal that the peptides template the growth of polycrystalline HA crystals .about.40 nm in size.

  5. [Larval survival and growth of Arbacia punctulata (Echinodermata: Echinoidea) fed with five micro-algae at two salinities].

    PubMed

    García, Marina; Rosas, Jesús; Hernández, Iván; Velásquez, Aidé; Cabrera, Tomas; Maneiro, Carlos

    2005-12-01

    Fertilized eggs from an spontaneously spawn of thirty sexually mature sea urchins (Arbacia punctulata) were incubated to complete embryonic development. The echinopluteus larvae (3 ind/ml) were distributed into 50 plastic containers (25 containers at 30 psu and 25 containers at 40 psu) and fed on Tetraselmis chuii, Nannochloropsis oculata, Isochrysis galbana, Chaetoceros gracilis and C. calcitrans under a natural photoperiod. The water of the containers was partially renewed (75%) everyday. Larval anatomic development aspects, daily survival and growth were determined. The growth was determined through postoral arms and body length measurement, and body diameter of twelve larvae during metamorphosis. During the planktonic larval phase, only the I. galbana diet produced similar results for both salinities. The relative growth of larvae was isometric (I) for larvae fed on I. galbana at two salinities and positive allometric for those fed on C. gracilis and C. calcitrans at both salinities. In this study A. punctulata started metamorphosis at day 14 and was completed 30 days after fecundation. Significant differences were detected in post-settlement body growth between the two salinities (F = 23.58, p < 0.05): growth was better for larvae at 30 psu (final body diameter was 3.14 +/- 0.44 mm). The final rate of planktonic larvae was highest with I. galbana (58.33%). For juveniles the rate was 6.48% for those fed on C. gracilis (40 psu in both larvae and juveniles). We recommend the use of this diet and 40 psu for survival or 30 psu for growth. PMID:17469263

  6. Fighting arboviral diseases: low toxicity on mammalian cells, dengue growth inhibition (in vitro), and mosquitocidal activity of Centroceras clavulatum-synthesized silver nanoparticles.

    PubMed

    Murugan, Kadarkarai; Aruna, Palanimuthu; Panneerselvam, Chellasamy; Madhiyazhagan, Pari; Paulpandi, Manickam; Subramaniam, Jayapal; Rajaganesh, Rajapandian; Wei, Hui; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Nicoletti, Marcello; Syuhei, Ban; Canale, Angelo; Benelli, Giovanni

    2016-02-01

    Dengue is a mosquito-borne viral disease that has rapidly spread in all regions of the world in recent years. Female mosquitoes, mainly Aedes aegypti, transmit dengue. Approximately 3,900 million people, in 128 countries, are at risk of dengue infection. Recently, a focus has been provided on the potential of green-synthesized nanoparticles as inhibitors of the production of dengue viral envelope (E) protein in Vero cells and downregulators of the expression of dengue viral E gene. Algae are an outstanding reservoir of novel compounds, which may help in the fight against mosquito-borne diseases. In this research, silver nanoparticles (AgNP) were rapidly synthesized using a cheap extract of the alga Centroceras clavulatum. AgNP were characterized by UV–vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). In mosquitocidal assays, LC50 values of C. clavulatum extract against A. aegypti larvae and pupae were 269.361 ppm (larva I), 309.698 ppm (larva II), 348.325 ppm (larva III), 387.637 ppm (larva IV), and 446.262 ppm (pupa). C. clavulatum extract also exhibited moderate antioxidant activity, both in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays. LC50 values of C. clavulatum-synthesized AgNP were 21.460 ppm (larva I), 23.579 ppm (larva II), 25.912 ppm (larva III), 29.155 ppm (larva IV), and 33.877 ppm (pupa). Furthermore, C. clavulatum-synthesized AgNP inhibited dengue (serotype dengue virus type-2 (DEN-2)) viral replication in Vero cells. Notably, 50 μg/ml of green-synthesized AgNP showed no cytotoxicity on Vero cells while reduced DEN-2 viral growth of more than 80%; 12.5 μg/ml inhibited viral growth of more than 50%. Cellular internalization assays highlighted that untreated infected cells showed high intensity of fluorescence emission, which denotes high level of viral internalization. Conversely

  7. Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma.

    PubMed

    Andersen, Nicholas J; Nickoloff, Brian J; Dykema, Karl J; Boguslawski, Elissa A; Krivochenitser, Roman I; Froman, Roe E; Dawes, Michelle J; Baker, Laurence H; Thomas, Dafydd G; Kamstock, Debra A; Kitchell, Barbara E; Furge, Kyle A; Duesbery, Nicholas S

    2013-09-01

    Angiosarcoma is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. As a model for human angiosarcoma, we studied primary cells and tumorgrafts derived from canine hemangiosarcoma (HSA), which is also an endothelial malignancy with similar presentation and histology. Primary cells isolated from HSA showed constitutive extracellular signal-regulated kinase (ERK) activation. The mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor CI-1040 reduced ERK activation and the viability of primary cells derived from visceral, cutaneous, and cardiac HSA in vitro. HSA-derived primary cells were also sensitive to sorafenib, an inhibitor of B-Raf and multireceptor tyrosine kinases. In vivo, CI-1040 or PD0325901 decreased the growth of cutaneous cell-derived xenografts and cardiac-derived tumorgrafts. Sorafenib decreased tumor size in both in vivo models, although cardiac tumorgrafts were more sensitive. In human angiosarcoma, we noted that 50% of tumors stained positively for phosphorylated ERK1/2 and that the expression of several MEK-responsive transcription factors was upregulated. Our data showed that MEK signaling is essential for the growth of HSA in vitro and in vivo and provided evidence that the same pathways are activated in human angiosarcoma. This indicates that MEK inhibitors may form part of an effective therapeutic strategy for the treatment of canine HSA or human angiosarcoma, and it highlights the use of spontaneous canine cancers as a model of human disease. PMID:23804705

  8. Pharmacologic inhibition of MEK signaling prevents growth of canine hemangiosarcoma

    PubMed Central

    Andersen, Nicholas J.; Nickoloff, Brian J.; Dykema, Karl J.; Boguslawski, Elissa A.; Krivochenitser, Roman I.; Froman, Roe E.; Dawes, Michelle J.; Baker, Laurence H.; Thomas, Dafydd G.; Kamstock, Debra A.; Kitchell, Barbara E.; Furge, Kyle A.; Duesbery, Nicholas S.

    2013-01-01

    Angiosarcoma (AS) is a rare neoplasm of endothelial origin that has limited treatment options and poor five-year survival. As a model for human AS, we studied primary cells and tumorgrafts derived from canine hemangiosarcoma (HSA), which is also an endothelial malignancy with similar presentation and histology. Primary cells isolated from HSA showed constitutive ERK activation. The MEK inhibitor CI-1040 reduced ERK activation and the viability of primary cells derived from visceral, cutaneous, and cardiac HSA in vitro. HSA-derived primary cells were also sensitive to sorafenib, an inhibitor of B-Raf and multi-receptor tyrosine kinases. In vivo, CI-1040 or PD0325901 decreased the growth of cutaneous cell-derived xenografts and cardiac-derived tumorgrafts. Sorafenib decreased tumor size in both in vivo models, although cardiac tumorgrafts were more sensitive. In human AS, we noted that 50% of tumors stained positively for phosphorylated ERK1/2 and that the expression of several MEK-responsive transcription factors was up-regulated. Our data showed that MEK signaling is essential for the growth of HSA in vitro and in vivo and provided evidence that the same pathways are activated in human AS. This indicates that MEK inhibitors may form part of an effective therapeutic strategy for the treatment of canine HSA or human AS, and it highlights the utility of spontaneous canine cancers as a model of human disease. PMID:23804705

  9. Elevated major ion concentrations inhibit larval mayfly growth and development.

    PubMed

    Johnson, Brent R; Weaver, Paul C; Nietch, Christopher T; Lazorchak, James M; Struewing, Katherine A; Funk, David H

    2015-01-01

    Anthropogenic disturbances, including those from developing energy resources, can alter stream chemistry significantly by elevating total dissolved solids. Field studies have indicated that mayflies (Order Ephemeroptera) are particularly sensitive to high total dissolved solids. In the present study, the authors measured 20-d growth and survivorship of larval Neocloeon triangulifer exposed to a gradient of brine salt (mixed NaCl and CaCl2 ) concentrations. Daily growth rates were reduced significantly in all salt concentrations above the control (363 µS cm(-1) ) and larvae in treatments with specific conductance >812 µS cm(-1) were in comparatively earlier developmental stages (instars) at the end of the experiment. Survivorship declined significantly when specific conductance was >1513 µS cm(-1) and the calculated 20-d 50% lethal concentration was 2866 µS cm(-1) . The present study's results provide strong experimental evidence that elevated ion concentrations similar to those observed in developing energy resources, such as oil and gas drilling or coal mining, can adversely affect sensitive aquatic insect species. PMID:25307284

  10. Microbial growth on hydrocarbons: terminal branching inhibits biodegradation.

    PubMed Central

    Schaeffer, T L; Cantwell, S G; Brown, J L; Watt, D S; Fall, R R

    1979-01-01

    A variety of octane-utilizing bacteria and fungi were screened for growth on some terminally branched dimethyloctane derivatives to explore the effects of iso- and anteiso-termini on the biodegradability of such hydrocarbons. Of 27 microbial strains tested, only 9 were found to use any of the branched hydrocarbons tested as a sole carbon source, and then only those hydrocarbons containing at least one iso-terminus were susceptible to degradation. Anteiso-or isopropenyl termini prevented biodegradation. None of the hydrocarbonoclastic yeasts tested was able to utilize branched-hydrocarbon growth sustrates. In the case of pseudomonads containing the OCT plasmid, whole-cell oxidation of n-octane was poorly induced by terminally branched dimethyloctanes. In the presence of a gratuitous inducer of the octane-oxidizing enzymes, the iso-branched 2,7-dimethyloctane was slowly oxidized by whole cells, whereas the anteiso-branched 3,6-dimethyloctane was not oxidized at all. This microbial sampling dramatically illustrated the deleterious effect of alkyl branching, especially anteiso-terminal branching, on the biodegradation of hydrocarbons. PMID:539824

  11. Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

    PubMed

    Vannini, Federica; Chattopadhyay, Mitali; Kodela, Ravinder; Rao, Praveen P N; Kashfi, Khosrow

    2015-12-01

    We recently reported the synthesis of NOSH-aspirin, a novel hybrid that releases both nitric oxide (NO) and hydrogen sulfide (H2S). In NOSH-aspirin, the two moieties that release NO and H2S are covalently linked at the 1, 2 positions of acetyl salicylic acid, i.e. ortho-NOSH-aspirin (o-NOSH-aspirin). In the present study, we compared the effects of the positional isomers of NOSH-ASA (o-NOSH-aspirin, m-NOSH-aspirin and p-NOSH-aspirin) to that of aspirin on growth of HT-29 and HCT 15 colon cancer cells, belonging to the same histological subtype, but with different expression of cyclooxygenase (COX) enzymes; HT-29 express both COX-1 and COX-2, whereas HCT 15 is COX-null. We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells. Since the parent compound aspirin, inhibits both COX-1 and COX-2, we also evaluated the effects of these compounds on COX-1 and COX-2 enzyme activities and also performed modeling of the interactions between the positional isomers of NOSH-aspirin and COX-1 and COX-2 enzymes. We observed that the three positional isomers of NOSH aspirin inhibited the growth of both colon cancer cell lines with IC50s in the nano-molar range. In particular in HT-29 cells the IC50s for growth inhibition were: o-NOSH-ASA, 0.04±0.011 µM; m-NOSH-ASA, 0.24±0.11 µM; p-NOSH-ASA, 0.46±0.17 µM; and in HCT 15 cells the IC50s for o-NOSH-ASA, m-NOSH-ASA, and p-NOSH-ASA were 0.062 ±0.006 µM, 0.092±0.004 µM, and 0.37±0.04 µM, respectively. The IC50 for aspirin in both cell lines was >5mM at 24h. The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis. All 3 positional isomers of NOSH-aspirin preferentially inhibited COX-1 over COX-2. These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential. PMID:26319435

  12. Multikinase inhibitor regorafenib inhibits the growth and metastasis of colon cancer with abundant stroma.

    PubMed

    Takigawa, Hidehiko; Kitadai, Yasuhiko; Shinagawa, Kei; Yuge, Ryo; Higashi, Yukihito; Tanaka, Shinji; Yasui, Wataru; Chayama, Kazuaki

    2016-05-01

    Interaction between tumor cells and stromal cells plays an important role in the growth and metastasis of colon cancer. We previously found that carcinoma-associated fibroblasts (CAFs) expressed platelet-derived growth factor receptor-β (PDGFR-β) and that PDGFR targeted therapy using imatinib or nilotinib inhibited stromal reaction. Bone marrow-derived mesenchymal stem cells (MSCs) migrate to tumor stroma and differentiate into CAFs. A novel oral multikinase inhibitor regorafenib inhibits receptor tyrosine kinases expressed on stromal cells (vascular endothelial growth factor receptor 1-3, TIE2, PDGFR-β, and fibroblast growth factors) and tumor cells (c-KIT, RET, and BRAF). These molecules are involved in tumor growth, angiogenesis, lymphangiogenesis, and stromal activation. Therefore, we examined whether regorafenib impaired the tumor-promoting effect of CAFs/MSCs. KM12SM human colon cancer cells alone or KM12SM cells with MSCs were transplanted into the cecal wall of nude mice. Co-implantation of KM12SM cells with MSCs into the cecal wall of nude mice produced tumors with abundant stromal component and promoted tumor growth and lymph node metastasis. Single treatment with regorafenib inhibited tumor growth and metastasis by inhibiting both tumor cells and stromal reaction. This tumor-inhibitory effect of regorafenib was more obvious in tumors developed by co-implanting KM12SM cells with MSCs. Our data suggested that targeting of the tumor microenvironment with regorafenib affected tumor cell-MSC interaction, which in turn inhibited the growth and metastasis of colon cancer. PMID:26865419

  13. Microbial growth inhibition by alternating electric fields in mice with Pseudomonas aeruginosa lung infection.

    PubMed

    Giladi, Moshe; Porat, Yaara; Blatt, Alexandra; Shmueli, Esther; Wasserman, Yoram; Kirson, Eilon D; Palti, Yoram

    2010-08-01

    High-frequency, low-intensity electric fields generated by insulated electrodes have previously been shown to inhibit bacterial growth in vitro. In the present study, we tested the effect of these antimicrobial fields (AMFields) on the development of lung infection caused by Pseudomonas aeruginosa in mice. We demonstrate that AMFields (10 MHz) significantly inhibit bacterial growth in vivo, both as a stand-alone treatment and in combination with ceftazidime. In addition, we show that peripheral (skin) heating of about 2 degrees C can contribute to bacterial growth inhibition in the lungs of mice. We suggest that the combination of alternating electric fields, together with the heat produced during their application, may serve as a novel antibacterial treatment modality. PMID:20547811

  14. Hydroperoxide lyase products, hexanal, hexenal and nonenal, inhibit soybean seedling growth

    SciTech Connect

    Gardner, H.W.; Dornbos, D.L. Jr. )

    1989-04-01

    Hexanal, a product of hydroperoxide lyase, inhibited the germination and growth of soybean seeds. Hexanal was continuously delivered to germinating seeds as a vapor dissolved in air with a flow-through system (100 ml/min). Only 0.8 {mu}g hexanal/ml air was required to inhibit seedling growth by 50%; nearly 100% inhibition occurred with a dose of 1.8 {mu}g hexanal/ml air. In the absence of hexanal brown spots were often visible on the seedlings, but at sublethal doses of hexanal, the seedlings were largely devoid of these spots. The relative toxicity of three hydroperoxide lyase products, hexanal, trans-2-hexanal and trans-2-nonenal, were compared with a Petri-dish bioassay. The order of toxicity against seedling growth was hexenal>hexanal>nonenal.

  15. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

    PubMed Central

    Boulter, Luke; Guest, Rachel V.; Kendall, Timothy J.; Wilson, David H.; Wojtacha, Davina; Robson, Andrew J.; Ridgway, Rachel A.; Samuel, Kay; Van Rooijen, Nico; Barry, Simon T.; Wigmore, Stephen J.; Sansom, Owen J.; Forbes, Stuart J.

    2015-01-01

    Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the WNT pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of WNT signaling with one of two small molecule WNT inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced WNT signaling is a characteristic of CC and suggest that targeting WNT signaling pathways has potential as a therapeutic strategy for CC. PMID:25689248

  16. Modeling synergistic drug inhibition of Mycobacterium tuberculosis growth in murine macrophages.

    PubMed

    Fang, Xin; Wallqvist, Anders; Reifman, Jaques

    2011-09-01

    We developed a metabolism-based systems biology framework to model drug-induced growth inhibition of Mycobacterium tuberculosis in murine macrophage cells. We used it to simulate ex vivo bacterial growth inhibition due to 3-nitropropionate (3-NP) and calculated the corresponding time- and drug concentration-dependent dose-response curves. 3-NP targets the isocitrate lyase 1 (ICL1) and ICL2 enzymes in the glyoxylate shunt, an essential component in carbon metabolism of many important prokaryotic organisms. We used the framework to in silico mimic drugging additional enzymes in combination with 3-NP to understand how synergy can arise among metabolic enzyme targets. In particular, we focused on exploring additional targets among the central carbon metabolism pathways and ascertaining the impact of jointly inhibiting these targets and the ICL1/ICL2 enzymes. Thus, additionally inhibiting the malate synthase (MS) enzyme in the glyoxylate shunt did not produce synergistic effects, whereas additional inhibition of the glycerol-3-phosphate dehydrogenase (G3PD) enzyme showed a reduction in bacterial growth beyond what each single inhibition could achieve. Whereas the ICL1/ICL2-MS pair essentially works on the same branch of the metabolic pathway processing lipids as carbon sources (the glyoxylate shunt), the ICL1/ICL2-G3PD pair inhibition targets different branches among the lipid utilization pathways. This allowed the ICL1/ICL2-G3PD drug combination to synergistically inhibit carbon processing and ultimately affect cellular growth. Our previously developed model for in vitro conditions failed to capture these effects, highlighting the importance of constructing accurate representations of the experimental ex vivo macrophage system. PMID:21713281

  17. Modelling the effects of pulse exposure of several PSII inhibitors on two algae.

    PubMed

    Copin, Pierre-Jean; Chèvre, Nathalie

    2015-10-01

    Subsequent to crop application and during precipitation events, herbicides can reach surface waters in pulses of high concentrations. These pulses can exceed the Annual Average Environmental Quality Standards (AA-EQS), defined in the EU Water Framework Directive, which aims to protect the aquatic environment. A model was developed in a previous study to evaluate the effects of pulse exposure for the herbicide isoproturon on the alga Scenedesmus vacuolatus. In this study, the model was extended to other substances acting as photosystem II inhibitors and to other algae. The measured and predicted effects were equivalent when pulse exposure of atrazine and diuron were tested on S. vacuolatus. The results were consistent for isoproturon on the alga Pseudokirchneriella subcapitata. The model is thus suitable for the effect prediction of phenylureas and triazines and for the algae used: S. vacuolatus and P. subcapitata. The toxicity classification obtained from the dose-response curves (diuron>atrazine>isoproturon) was conserved for the pulse exposure scenarios modelled for S. vacuolatus. Toxicity was identical for isoproturon on the two algae when the dose-response curves were compared and also for the pulse exposure scenarios. Modelling the effects of any pulse scenario of photosystem II inhibitors on algae is therefore feasible and only requires the determination of the dose-response curves of the substance and growth rate of unexposed algae. It is crucial to detect the longest pulses when measurements of herbicide concentrations are performed in streams because the model showed that they principally affect the cell density inhibition of algae. PMID:26011414

  18. Thalassemic erythrocytes inhibit in vitro growth of Plasmodium falciparum.

    PubMed Central

    Brockelman, C R; Wongsattayanont, B; Tan-ariya, P; Fucharoen, S

    1987-01-01

    Blood specimens from 100 thalassemic patients were screened in vitro for inhibitory effects on growth and multiplication of Plasmodium falciparum. The culture medium mixture designated REM consisted of 9 volumes of minimum essential medium (GIBCO Laboratories, Grand Island, N.Y.) and 1 volume of RPMI 1640 (GIBCO) supplemented with 10% heat-inactivated human serum. Parasite multiplication in erythrocytes containing normal hemoglobin cultured in RPMI or REM was similar. Significant reduction in parasite multiplication rates was observed in erythrocytes containing abnormal hemoglobin when these were cultured in REM. The degree of reduction in five types of thalassemic erythrocytes was in the following descending order: hemoglobin H disease with Hb Constant Spring, classical hemoglobin H disease, beta(0)-thalassemia-hemoglobin E in which blood harbored a high percentage of hemoglobin F-containing cells, beta (0)-thalassemia-hemoglobin E in which blood harbored few hemoglobin F-containing cells, and beta-thalassemia heterozygous variant. PMID:3539999

  19. Carbon Monoxide Expedites Metabolic Exhaustion to Inhibit Tumor Growth

    PubMed Central

    Wegiel, Barbara; Gallo, David; Csizmadia, Eva; Harris, Clair; Belcher, John; Vercellotti, Gregory M.; Penacho, Nuno; Seth, Pankaj; Sukhatme, Vikas; Ahmed, Asif; Pandolfi, Pier Paolo; Helczynski, Leszek; Bjartell, Anders; Persson, Jenny Liao; Otterbein, Leo E

    2013-01-01

    One classical feature of cancer cells is their metabolic acquisition of a highly glycolytic phenotype. Carbon monoxide (CO), one of the products of the cytoprotective molecule heme oxygenase-1 (HO-1) in cancer cells, has been implicated in carcinogenesis and therapeutic resistance. However, the functional contributions of CO and HO-1 to these processes are poorly defined. In human prostate cancers, we found that HO-1 was nuclear localized in malignant cells, with low enzymatic activity in moderately differentiated tumors correlating with relatively worse clinical outcomes. Exposure to CO sensitized prostate cancer cells but not normal cells to chemotherapy, with growth arrest and apoptosis induced in vivo in part through mitotic catastrophe. CO targeted mitochondria activity in cancer cells as evidenced by higher oxygen consumption, free radical generation and mitochondrial collapse. Collectively, our findings indicated that CO transiently induces an anti-Warburg effect by rapidly fueling cancer cell bioenergetics, ultimately resulting in metabolic exhaustion. PMID:24121491

  20. Study of coloration, microbe inhibition during the growth of L-arginine phosphate monohydrate single crystals

    NASA Astrophysics Data System (ADS)

    Li, Aidong; Xu, Chongquan; Li, Aibin; Ming, Naiben

    2000-12-01

    During the growth of L-arginine phosphate monohydrate (LAP) single crystals, the problems of coloration and microbial contamination of the solution were investigated. It was found that the solution coloration can be prevented by conducting crystal growth at temperatures lower than 40°C and by inhibiting microbial growth. Compared to the known microbe inhibitors H 2O 2 and n-hexane, liquid paraffin shows advantages of long durability and convenience of usage for the growth of high-quality LAP single crystals.

  1. Xanthatin, a novel potent inhibitor of VEGFR2 signaling, inhibits angiogenesis and tumor growth in breast cancer cells

    PubMed Central

    Yu, Yao; Yu, Jing; Pei, Chong Gang; Li, Yun Yan; Tu, Ping; Gao, Gui Ping; Shao, Yi

    2015-01-01

    Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as an important tool for cancer treatment. In this study, we described a novel VEGFR2 inhibitor, xanthatin, which inhibits tumor angiogenesis and growth. The biochemical profiles of xanthatin were investigated using kinase assay, migration assay, tube formation, Matrigel plug assay, western blot, immunofluorescence and human tumor xenograft model. Xanthatin significantly inhibited growth, migration and tube formation of human umbilical vascular endothelial cell as well as inhibited vascular endothelial growth factor (VEGF)-stimulated angiogenesis. In addition, it inhibited VEGF-induced phosphorylation of VEGFR2 and its downstream signaling regulator. Moreover, xanthatin directly inhibit proliferation of breast cancer cells MDA-MB-231. Oral administration of xanthatin could markedly inhibit human tumor xenograft growth and decreased microvessel densities (MVD) in tumor sections. Taken together, these preclinical evaluations suggest that xanthatin inhibits angiogenesis and may be a promising anticancer drug candidate. PMID:26617743

  2. Platycodin D inhibits tumor growth by antiangiogenic activity via blocking VEGFR2-mediated signaling pathway

    SciTech Connect

    Luan, Xin; Gao, Yun-Ge; Guan, Ying-Yun; Xu, Jian-Rong; Lu, Qin; Zhao, Mei; Liu, Ya-Rong; Liu, Hai-Jun; Fang, Chao; Chen, Hong-Zhuan

    2014-11-15

    Platycodin D (PD) is an active component mainly isolated from the root of Platycodon grandiflorum. Recent studies proved that PD exhibited inhibitory effect on proliferation, migration, invasion and xenograft growth of diverse cancer cell lines. However, whether PD is suppressive for angiogenesis, an important hallmark in cancer development, remains unknown. Here, we found that PD could dose-dependently inhibit human umbilical vein endothelial cell (HUVEC) proliferation, motility, migration and tube formation. PD also significantly inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM). Moreover, the antiangiogenic activity of PD contributed to its in vivo anticancer potency shown in the decreased microvessel density and delayed growth of HCT-15 xenograft in mice with no overt toxicity. Western blot analysis indicated that PD inhibited the phosphorylation of VEGFR2 and its downstream protein kinase including PLCγ1, JAK2, FAK, Src, and Akt in endothelial cells. Molecular docking simulation showed that PD formed hydrogen bonds and hydrophobic interactions within the ATP binding pocket of VEGFR2 kinase domain. The present study firstly revealed the high antiangiogenic activity and the underlying molecular basis of PD, suggesting that PD may be a potential antiangiogenic agent for angiogenesis-related diseases. - Highlights: • Platycodin D inhibits HUVEC proliferation, motility, migration and tube formation. • Platycodin D inhibits the angiogenesis in chick embryo chorioallantoic membrane. • Platycodin D suppresses the angiogenesis and growth of HCT-15 xenograft in mice. • Platycodin D inhibits the phosphorylation of VEGFR2 and downstream kinases in HUVEC.

  3. Toxicity and accumulation of copper and cadmium in the alga Scenedesmus obliquus LH

    SciTech Connect

    Drbal, K.; Veber, K.; Zahradnik, J.

    1985-06-01

    The techniques of determination of toxic and inhibitory effects, and of measuring the kinetics of metal sorption, used by individual authors differ widely in basic parameters, especially in the experimental concentrations of algal suspensions and in methods of separation of algae. Some authors assume that the drop in the concentration of the metal in the solution, or its concentration in the biomass, are a measure of sorption of the metals by the algae. This is not entirely correct; our study led to this conclusion on the basis of measurement of inhibition of growth and sorption of copper and cadmium ions in dense algal suspensions in a photoautotrophic regime of an intensive culture, and comparison of disappearance of these ions from the solution in the absence of the algae.

  4. Siting algae cultivation facilities for biofuel production in the United States: trade-offs between growth rate, site constructability, water availability, and infrastructure

    SciTech Connect

    Venteris, Erik R.; McBride, Robert; Coleman, Andre M.; Skaggs, Richard; Wigmosta, Mark S.

    2014-02-21

    Locating sites for new algae cultivation facilities is a complex task. The climate must support high growth rates, and cultivation ponds require appropriate land and water resources as well as key utility and transportation infrastructure. We employ our spatiotemporal Biomass Assessment Tool (BAT) to select promising locations based on the open-pond cultivation of Arthrospira sp. and a strain of the order Desmidiales. 64,000 potential sites across the southern United States were evaluated. We progressively apply a range of screening criteria and track their impact on the number of selected sites, geographic location, and biomass productivity. Both strains demonstrate maximum productivity along the Gulf of Mexico coast, with the highest values on the Florida peninsula. In contrast, sites meeting all selection criteria for Arthrospira were located along the southern coast of Texas and for Desmidiales were located in Louisiana and southern Arkansas. Site selection was driven mainly by the lack of oil pipeline access in Florida and elevated groundwater salinity in southern Texas. The requirement for low salinity freshwater (<400 mg L-1) constrained Desmidiales locations; siting flexibility is greater for salt-tolerant species such as Arthrospira. Combined siting factors can result in significant departures from regions of maximum productivity but are within the expected range of site-specific process improvements.

  5. Siting algae cultivation facilities for biofuel production in the United States: trade-offs between growth rate, site constructability, water availability, and infrastructure.

    PubMed

    Venteris, Erik R; McBride, Robert C; Coleman, Andre M; Skaggs, Richard L; Wigmosta, Mark S

    2014-03-18

    Locating sites for new algae cultivation facilities is a complex task. The climate must support high growth rates, and cultivation ponds require appropriate land and water resources, as well as transportation and utility infrastructure. We employ our spatiotemporal Biomass Assessment Tool (BAT) to select promising locations based on the open-pond cultivation of Arthrospira sp. and strains of the order Sphaeropleales. A total of 64,000 sites across the southern United States were evaluated. We progressively applied screening criteria and tracked their impact on the number of potential sites, geographic location, and biomass productivity. Both strains demonstrated maximum productivity along the Gulf of Mexico coast, with the highest values on the Florida peninsula. In contrast, sites meeting all selection criteria for Arthrospira were located along the southern coast of Texas and for Sphaeropleales were located in Louisiana and southern Arkansas. Results were driven mainly by the lack of oil pipeline access in Florida and elevated groundwater salinity in southern Texas. The requirement for low-salinity freshwater (<400 mg L(-1)) constrained Sphaeropleales locations; siting flexibility is greater for salt-tolerant species like Arthrospira. Combined siting factors can result in significant departures from regions of maximum productivity but are within the expected range of site-specific process improvements. PMID:24559117

  6. Ketoprofen S(+) enantiomer inhibits prostaglandin production and cell growth in 3T6 fibroblast cultures.

    PubMed

    Sánchez, T; Moreno, J J

    1999-04-01

    The ketoprofen S(+) enantiomer inhibits with great stereoselectivity both prostaglandin H synthase isoenzymes. Thus, the biological effects of ketoprofen on inflammation are due almost entirely to the S(+) isomer. Here, we report that the S(+) enantiomer, at doses that inhibit prostaglandin synthesis, is effective in reducing DNA synthesis and 3T6 fibroblast growth. Our data suggest that prostaglandins are involved in the control of 3T6 fibroblast growth and that the effect of the ketoprofen S(+) enantiomer on 3T6 proliferation is correlated with its effects on prostaglandin H synthase and prostaglandin production. PMID:10323281

  7. Isonicotinic acid hydrazide inhibits cell population growth during teratogenesis of chick embryo.

    PubMed

    Joshi, M V; Shah, V B; Modak, S P

    1991-01-01

    In chick embryos treated with a 4 hr pulse of 7.2 X 10(-5) M isonicotinic acid hydrazide (INH) the cell population growth is inhibited with an increased population doubling time. Teratogenised blastoderm cells complete their ongoing cell cycle and arrest in G1 phase. A chase with an equimolar concentration of pyridoxal-5-phosphate restores the growth rate after a lag of 4 hr equivalent to the duration of treatment with INH. Presumptive mesoblast cells invaginated through the primitive streak and neuroectoblast cells induced prior to the application of INH differentiate, while the teratogen inhibits morphogenesis and organization of organ primordia. PMID:1864614

  8. Calcium influences sensitivity to growth inhibition induced by a cell surface sialoglycopeptide

    NASA Technical Reports Server (NTRS)

    Betz, N. A.; Fattaey, H. K.; Johnson, T. C.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    While studies concerning mitogenic factors have been an important area of research for many years, much less is understood about the mechanisms of action of cell surface growth inhibitors. We have purified an 18 kDa cell surface sialoglycopeptide growth inhibitor (CeReS-18) which can reversibly inhibit the proliferation of diverse cell types. The studies discussed in this article show that three mouse keratinocyte cell lines exhibit sixty-fold greater sensitivity than other fibroblasts and epithelial-like cells to CeReS-18-induced growth inhibition. Growth inhibition induced by CeReS-18 treatment is a reversible process, and the three mouse keratinocyte cell lines exhibited either single or multiple cell cycle arrest points, although a predominantly G0/G1 cell cycle arrest point was exhibited in Swiss 3T3 fibroblasts. The sensitivity of the mouse keratinocyte cell lines to CeReS-18-induced growth inhibition was not affected by the degree of tumorigenic progression in the cell lines and was not due to differences in CeReS-18 binding affinity or number of cell surface receptors per cell. However, the sensitivity of both murine fibroblasts and keratinocytes could be altered by changing the extracellular calcium concentration, such that increased extracellular calcium concentrations resulted in decreased sensitivity to CeReS-18-induced proliferation inhibition. Thus the increased sensitivity of the murine keratinocyte cell lines to CeReS-18 could be ascribed to the low calcium concentration used in their propagation. Studies are currently under way investigating the role of calcium in CeReS-18-induced growth arrest. The CeReS-18 may serve as a very useful tool to study negative growth control and the signal transduction events associated with cell cycling.

  9. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model.

    PubMed

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-03-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  10. In vitro inhibition of Helicobacter pylori growth and adherence to gastric mucosal cells by Pycnogenol.

    PubMed

    Rohdewald, Peter; Beil, Winfried

    2008-05-01

    The emergence of antibiotic resistant H. pylori strains has necessitated the identification of alternative additive therapies for the treatment of this infection. The study tested whether a specific pine bark extract (Pycnogenol is effective in inhibiting the growth and adherence of H. pylori in vitro. Inhibition of H. pylori growth by Pycnogenol was tested in liquid medium as well as in an in vitro model by using sessile bacteria attached to AGS cells. Adherence was determined by co-incubation of gastric cells with Pycnogenol and H. pylori in vitro. Pycnogenol inhibited H. pylori growth in suspension with an MIC(50) of 12.5 microg/mL. Growth of H. pylori in infected cells was reduced to 10% of the control value by 125 microg/mL Pycnogenol. Adherence of H. pylori to gastric cells was reduced by 70% after 3 h incubation with 125 microg/mL Pycnogenol. The results show a significant, yet limited inhibition of growth and adherence of H. pylori to gastric cells by Pycnogenol. In vivo studies have to demonstrate the clinical relevance of these findings. PMID:18350522

  11. Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model

    PubMed Central

    Parajuli, Keshab Raj; Zhang, Qiuyang; Liu, Sen; You, Zongbing

    2016-01-01

    Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID:26840261

  12. The rhizobacterium Arthrobacter agilis produces dimethylhexadecylamine, a compound that inhibits growth of phytopathogenic fungi in vitro.

    PubMed

    Velázquez-Becerra, Crisanto; Macías-Rodríguez, Lourdes I; López-Bucio, José; Flores-Cortez, Idolina; Santoyo, Gustavo; Hernández-Soberano, Christian; Valencia-Cantero, Eduardo

    2013-12-01

    Plant diseases caused by fungal pathogens such as Botrytis cinerea and the oomycete Phytophthora cinnamomi affect agricultural production worldwide. Control of these pests can be done by the use of fungicides such as captan, which may have deleterious effects on human health. This study demonstrates that the rhizobacterium Arthrobacter agilis UMCV2 produces volatile organic compounds that inhibit the growth of B. cinerea in vitro. A single compound from the volatile blends, namely dimethylhexadecylamine (DMHDA), could inhibit the growth of both B. cinerea and P. cinnamomi when supplied to the growth medium in low concentrations. DMHDA also inhibited the growth of beneficial fungi Trichoderma virens and Trichoderma atroviride but at much higher concentrations. DMHDA-related aminolipids containing 4, 8, 10, 12, and 14 carbons in the alkyl chain were tested for their inhibitory effect on the growth of the pathogens. The results show that the most active compound from those tested was dimethyldodecylamine. This effect correlates with a decrease in the number of membrane lipids present in the mycelium of the pathogen including eicosanoic acid, (Z)-9-hexadecenoic acid, methyl ester, and (Z)-9-octadecenoic acid, methyl ester. Strawberry leaflets treated with DMHDA were not injured by the compound. These data indicate that DMHDA and related compounds, which can be produced by microorganisms may effectively inhibit the proliferation of certain plant pathogens. PMID:23674267

  13. Disrupting the Oncogenic Synergism between Nucleolin and Ras Results in Cell Growth Inhibition and Cell Death

    PubMed Central

    Schokoroy, Sari; Juster, Dolly; Kloog, Yoel; Pinkas-Kramarski, Ronit

    2013-01-01

    Background The ErbB receptors, Ras proteins and nucleolin are major contributors to malignant transformation. The pleiotropic protein nucleolin can bind to both Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk between Ras, nucleolin and the ErbB1 receptor. Activated Ras facilitates nucleolin interaction with ErbB1 and stabilizes ErbB1 levels. The three oncogenes synergistically facilitate anchorage independent growth and tumor growth in nude mice. Methodology/Principal Findings In the present study we used several cancer cell lines. The effect of Ras and nucleolin inhibition was determined using cell growth, cell death and cell motility assays. Protein expression was determined by immunohistochemistry. We found that inhibition of Ras and nucleolin reduces tumor cell growth, enhances cell death and inhibits anchorage independent growth. Our results reveal that the combined treatment affects Ras and nucleolin levels and localization. Our study also indicates that Salirasib (FTS, Ras inhibitor) reduces cell motility, which is not affected by the nucleolin inhibitor. Conclusions/Significance These results suggest that targeting both nucleolin and Ras may represent an additional avenue for inhibiting cancers driven by these oncogenes. PMID:24086490

  14. Formononetin, a novel FGFR2 inhibitor, potently inhibits angiogenesis and tumor growth in preclinical models

    PubMed Central

    Wu, Zhen Feng; Chen, Che; Liu, Jia Yun; Wu, Guan Nan; Yao, Xue Quan; Liu, Fu Kun; Li, Gang; Shen, Liang

    2015-01-01

    Most anti-angiogenic therapies currently being evaluated in clinical trials target vascular endothelial growth factor (VEGF) pathway, however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified formononetin as a novel agent with potential anti-angiogenic and anti-cancer activities. Formononetin demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor 2 (FGF2). In ex vivo and in vivo angiogenesis assays, formononetin suppressed FGF2-induced microvessel sprouting of rat aortic rings and angiogenesis. To understand the underlying molecular basis, we examined the effects of formononetin on different molecular components in treated endothelial cell, and found that formononetin suppressed FGF2-triggered activation of FGFR2 and protein kinase B (Akt) signaling. Moreover, formononetin directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer, formononetin showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Moreover, formononetin enhanced the effect of VEGFR2 inhibitor sunitinib on tumor growth inhibition. Taken together, our results indicate that formononetin targets the FGFR2-mediated Akt signaling pathway, leading to the suppression of tumor growth and angiogenesis. PMID:26575424

  15. Growth of antarctic cyanobacteria under ultraviolet radiation: UVA counteracts UVB inhibition

    SciTech Connect

    Quesada, A. |; Mouget, J.L.; Vincent, W.F.

    1995-04-01

    A mat-forming cyanobacterium (Phormidium murayi West and West) isolated from an ice-shelf pond in Antarctica was grown under white light combined with a range of UVA and UVB irradiance. The 4-day growth rate decreased under increasing ultraviolet (UV) radiation, with a ninefold greater response to UVB relative to UVA. In vivo absorbance spectra showed that UVA and to a greater extent UVB caused a decrease in phycocyanin/chlorophyll a and an increase in carotenoids/chlorophyll a. The phycocyanin/chlorophyll a ratio was closely and positively correlated to the UVB-inhibited growth rate. Under fixed spectral gradients of UV radiation, the growth inhibition effect was dominated by UVB. However, at specific UVB irradiances the inhibition of growth depended on the ratio of UVB to UVA, and growth rates increased linearly with increasing UVA. These results are consistent with the view that UVB inhibition represents the balance between damage and repair processes that are each controlled by separate wavebands. They also underscore the need to consider UV spectral balance in laboratory and field assays of UVB toxicity. 49 refs., 6 figs.

  16. Bee Venom Promotes Hair Growth in Association with Inhibiting 5α-Reductase Expression.

    PubMed

    Park, Seeun; Erdogan, Sedef; Hwang, Dahyun; Hwang, Seonwook; Han, Eun Hye; Lim, Young-Hee

    2016-06-01

    Alopecia is an important issue that can occur in people of all ages. Recent studies show that bee venom can be used to treat certain diseases including rheumatoid arthritis, neuralgia, and multiple sclerosis. In this study, we investigated the preventive effect of bee venom on alopecia, which was measured by applying bee venom (0.001, 0.005, 0.01%) or minoxidil (2%) as a positive control to the dorsal skin of female C57BL/6 mice for 19 d. Growth factors responsible for hair growth were analyzed by quantitative real-time PCR and Western blot analysis using mice skins and human dermal papilla cells (hDPCs). Bee venom promoted hair growth and inhibited transition from the anagen to catagen phase. In both anagen phase mice and dexamethasone-induced catagen phase mice, hair growth was increased dose dependently compared with controls. Bee venom inhibited the expression of SRD5A2, which encodes a type II 5α-reductase that plays a major role in the conversion of testosterone into dihydrotestosterone. Moreover, bee venom stimulated proliferation of hDPCs and several growth factors (insulin-like growth factor 1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)2 and 7) in bee venom-treated hDPCs dose dependently compared with the control group. In conclusion, bee venom is a potentially potent 5α-reductase inhibitor and hair growth promoter. PMID:27040904

  17. MicroRNA-18b inhibits the growth of malignant melanoma via inhibition of HIF-1α-mediated glycolysis.

    PubMed

    Chen, Yao; Zhang, Ziqing; Luo, Chengqun; Chen, Zizi; Zhou, Jianda

    2016-07-01

    MicroRNAs (miRs) have been demonstrated to play critical roles in the development and progression of malignant melanoma (MM). However, the exact role and underlying mechanism of miR-18b in MM growth remains unclear. In the present study, real-time PCR data indicated that miR-18b was significantly downregulated in MM tissues compared to their matched adjacent non-tumor tissues. Low miR-18b expression was significantly associated with the tumor thickness and stage, although no significant association was observed between the miR-18b expression and the age, gender, or lymph node metastasis. Besides, miR-18b was also significantly downregulated in MM B16 and A375 cells compared to normal skin HACAT cells. Ectopic expression of miR-18b decreased the proliferation of A375 and B16 cells, while induced a remarkable cell cycle arrest at G1 stage. Besides, miR-18b overexpression also inhibited the glycolysis in A375 and B16 cells. HIF-1α, a key regulator in glycolysis, was then identified as a target gene of miR-18b, and its expression was negatively mediated by miR-18b in A375 and B16 cells. Overexpression of HIF-1α rescued the suppressive effect of miR-18b on MM cell proliferation and glycolysis. In vivo study further showed that overexpression of miR-18b inhibited the MM growth as well as the tumor-related death, accompanied with HIF-1α downregulation. Taken together, the present study suggests that miR-18b inhibits the growth of MM cells in vitro and in vivo through directly targeting HIF-1α. PMID:27220837

  18. Epidermal growth factor receptor inhibition in lung cancer: status 2012.

    PubMed

    Hirsch, Fred R; Jänne, Pasi A; Eberhardt, Wilfried E; Cappuzzo, Federico; Thatcher, Nick; Pirker, Robert; Choy, Hak; Kim, Edward S; Paz-Ares, Luis; Gandara, David R; Wu, Yi-Long; Ahn, Myung-Ju; Mitsudomi, Tetsuya; Shepherd, Frances A; Mok, Tony S

    2013-03-01

    Lung cancer is the most common cause of cancer deaths. Most patients present with advanced-stage disease, and the prognosis is generally poor. However, with the understanding of lung cancer biology, and development of molecular targeted agents, there have been improvements in treatment outcomes for selected subsets of patients with non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated significantly improved tumor responses and progression-free survival in subsets of patients with advanced NSCLC, particularly those with tumors harboring activating EGFR mutations. Testing for EGFR mutations is a standard procedure for identification of patients who will benefit from first-line EGFR TKIs. For patients with advanced NSCLC and no activating EGFR mutations (EGFR wild-type) or no other driving oncogenes such as ALK-gene rearrangement, chemotherapy is still the standard of care. A new generation of EGFR TKIs, targeting multiple receptors and with irreversible bindings to the receptors, are in clinical trials and have shown encouraging effects. Research on primary and acquired resistant mechanisms to EGFR TKIs are ongoing. Monoclonal antibodies (e.g. cetuximab), in combination with chemotherapy, have demonstrated improved outcomes, particularly for subsets of NSCLC patients, but further validations are needed. Novel monoclonal antibodies are combined with chemotherapy, and randomized comparative studies are ongoing. This review summarizes the current status of EGFR inhibitors in NSCLC in 2012 and some of the major challenges we are facing. PMID:23370315

  19. Targeted Proapoptotic Peptides Depleting Adipose Stromal Cells Inhibit Tumor Growth.

    PubMed

    Daquinag, Alexes C; Tseng, Chieh; Zhang, Yan; Amaya-Manzanares, Felipe; Florez, Fernando; Dadbin, Ali; Zhang, Tao; Kolonin, Mikhail G

    2016-02-01

    Progression of many cancers is associated with tumor infiltration by mesenchymal stromal cells (MSC). Adipose stromal cells (ASC) are MSC that serve as adipocyte progenitors and endothelium-supporting cells in white adipose tissue (WAT). Clinical and animal model studies indicate that ASC mobilized from WAT are recruited by tumors. Direct evidence for ASC function in tumor microenvironment has been lacking due to unavailability of approaches to specifically inactivate these cells. Here, we investigate the effects of a proteolysis-resistant targeted hunter-killer peptide D-WAT composed of a cyclic domain CSWKYWFGEC homing to ASC and of a proapoptotic domain KLAKLAK2. Using mouse bone marrow transplantation models, we show that D-WAT treatment specifically depletes tumor stromal and perivascular cells without directly killing malignant cells or tumor-infiltrating leukocytes. In several mouse carcinoma models, targeted ASC cytoablation reduced tumor vascularity and cell proliferation resulting in hemorrhaging, necrosis, and suppressed tumor growth. We also validated a D-WAT derivative with a proapoptotic domain KFAKFAK2 that was found to have an improved cytoablative activity. Our results for the first time demonstrate that ASC, recruited as a component of tumor microenvironment, support cancer progression. We propose that drugs targeting ASC can be developed as a combination therapy complementing conventional cancer treatments. PMID:26316391

  20. Time-Dependent Effects in Algae for Chemicals with Different Adverse Outcome Pathways: A Novel Approach.

    PubMed

    Vogs, Carolina; Altenburger, Rolf

    2016-07-19

    Chemicals affect unicellular algae as a result of toxicokinetic and toxicodynamic processes. The internal concentration of chemicals in algae cells typically reaches equilibrium within minutes, while damage cumulatively increases over hours. The time gap between the steady state of internal exposure and damage development is thus suspected to span up to hours, mainly due to toxicodynamic processes. The quantification of rate-limited toxicodynamic processes, aggregated as a progressive effect from an initiating molecular event through biological key events toward the adverse outcome on algae growth inhibition, might discriminate between different adverse outcome pathways (AOPs). To support our hypothesis, we selected six chemicals according to different physicochemical properties and three distinctly dissimilar AOPs. The time courses of internal concentrations were linked to the observed affected Scenedesmus vacuolatus growth using toxicokinetic-toxicodynamic modeling. Effects on cell growth were explained by effect progression and not by the time to reach internal equilibrium concentration. Effect progression rates ranged over 6 orders of magnitude for all chemicals but varied by less than 1 order of magnitude within similar AOP (photosystem II inhibitors > reactive chemicals > lipid biosynthesis inhibitors), meaning that inhibitors of photosystem II advance an effect toward algae growth fastest compared to reactive chemicals and inhibitors of lipid biosynthesis. PMID:27149222

  1. Huanglian, A chinese herbal extract, inhibits cell growth by suppressing the expression of cyclin B1 and inhibiting CDC2 kinase activity in human cancer cells.

    PubMed

    Li, X K; Motwani, M; Tong, W; Bornmann, W; Schwartz, G K

    2000-12-01

    Huanglian is an herb that is widely used in China for the treatment of gastroenteritis. We elected to determine whether huanglian could inhibit tumor cell growth by modulating molecular events directly associated with the cell cycle. Huanglian inhibited tumor growth and colony formation of gastric, colon, and breast cancer cell lines in a time- and dose-dependent manner. Cell growth was completely inhibited after 3 days of continuous drug exposure to 10 microg/ml of herb. This degree of growth inhibition was significantly greater than that observed with berberine, the major constituent of the herb. The inhibition of cell growth by huanglian was associated with up to 8-fold suppression of cyclin B1 protein. This resulted in complete inhibition of cdc2 kinase activity and accumulation of cells in G(2). The mRNA expression of cyclin B1 was not changed after huanglian treatment. There was no change in the protein expression of cyclins A or E. Therefore, the effect of huanglian on inhibiting tumor growth seems to be mediated by the selective suppression of cyclin B1, which results in the inhibition of cdc2 kinase activity. Inhibition of cyclin dependent kinase (cdk) activity is emerging as an attractive target for cancer chemotherapy. Huanglian represents a class of agents that can inhibit tumor cell growth by directly suppressing the expression of a cyclin subunit that is critical for cell cycle progression. These results indicate that traditional Chinese herbs may represent a new source of agents designed for selective inhibition of cyclin dependent kinases in cancer therapy. PMID:11093765

  2. Breakdown of the coral-algae symbiosis: towards formalising a linkage between warm-water bleaching thresholds and the growth rate of the intracellular zooxanthellae

    NASA Astrophysics Data System (ADS)

    Wooldridge, S. A.

    2013-03-01

    Impairment of the photosynthetic machinery of the algal endosymbiont ("zooxanthellae") is the proximal driver of the thermal breakdown of the coral-algae symbiosis ("coral bleaching"). Yet, the initial site of damage, and early dynamics of the impairment are still not well resolved. In this perspective essay, I consider further a recent hypothesis which proposes an energetic disruption to the carbon-concentrating mechanisms (CCMs) of the coral host, and the resultant onset of CO2-limitation within the photosynthetic "dark reactions" as a unifying cellular mechanism. The hypothesis identifies the enhanced retention of photosynthetic carbon for zooxanthellae (re)growth following an initial irradiance-driven expulsion event as a strong contributing cause of the energetic disruption. If true, then it implies that the onset of the bleaching syndrome and setting of upper thermal bleaching limits are emergent attributes of the coral symbiosis that are ultimately underpinned by the characteristic growth profile of the intracellular zooxanthellae; which is known to depend not just on temperature, but also external (seawater) nutrient availability and zooxanthellae genotype. Here, I review this proposed bleaching linkage at a variety of observational scales, and find it to be parsimonious with the available evidence. Future experiments are suggested that can more formally test the linkage. If correct, the new cellular model delivers a valuable new perspective to consider the future prospects of the coral symbiosis in an era of rapid environmental change, including: (i) the underpinning mechanics (and biological significance) of observed changes in resident zooxanthellae genotypes, and (ii) the now crucial importance of reef water quality in co-determining thermal bleaching resistance.

  3. Nanoelectroablation of Murine Tumors Triggers a CD8-Dependent Inhibition of Secondary Tumor Growth

    PubMed Central

    Nuccitelli, Richard; Berridge, Jon Casey; Mallon, Zachary; Kreis, Mark; Athos, Brian; Nuccitelli, Pamela

    2015-01-01

    We have used both a rat orthotopic hepatocellular carcinoma model and a mouse allograft tumor model to study liver tumor ablation with nanosecond pulsed electric fields (nsPEF). We confirm that nsPEF treatment triggers apoptosis in rat liver tumor cells as indicated by the appearance of cleaved caspase 3 and 9 within two hours after treatment. Furthermore we provide evidence that nsPEF treatment leads to the translocation of calreticulin (CRT) to the cell surface which is considered a damage-associated molecular pattern indicative of immunogenic cell death. We provide direct evidence that nanoelectroablation triggers a CD8-dependent inhibition of secondary tumor growth by comparing the growth rate of secondary orthotopic liver tumors in nsPEF-treated rats with that in nsPEF-treated rats depleted of CD8+ cytotoxic T-cells. The growth of these secondary tumors was severely inhibited as compared to tumor growth in CD8-depleated rats, with their average size only 3% of the primary tumor size after the same one-week growth period. In contrast, when we depleted CD8+ T-cells the second tumor grew more robustly, reaching 54% of the size of the first tumor. In addition, we demonstrate with immunohistochemistry that CD8+ T-cells are highly enriched in the secondary tumors exhibiting slow growth. We also showed that vaccinating mice with nsPEF-treated isogenic tumor cells stimulates an immune response that inhibits the growth of secondary tumors in a CD8+-dependent manner. We conclude that nanoelectroablation triggers the production of CD8+ cytotoxic T-cells resulting in the inhibition of secondary tumor growth. PMID:26231031

  4. Auxin-Induced Ethylene Triggers Abscisic Acid Biosynthesis and Growth Inhibition1

    PubMed Central

    Hansen, Hauke; Grossmann, Klaus

    2000-01-01

    The growth-inhibiting effects of indole-3-acetic acid (IAA) at high concentration and the synthetic auxins 7-chloro-3-methyl-8-quinolinecarboxylic acid (quinmerac), 2-methoxy-3,6-dichlorobenzoic acid (dicamba), 4-amino-3,6,6-trichloropicolinic acid (picloram), and naphthalene acetic acid, were investigated in cleavers (Galium aparine). When plants were root treated with 0.5 mm IAA, shoot epinasty and inhibition of root and shoot growth developed during 24 h. Concomitantly, 1-aminocyclopropane-1-carboxylic acid (ACC) synthase activity, and ACC and ethylene production were transiently stimulated in the shoot tissue within 2 h, followed by increases in immunoreactive (+)-abscisic acid (ABA) and its precursor xanthoxal (xanthoxin) after 5 h. After 24 h of treatment, levels of xanthoxal and ABA were elevated up to 2- and 24-fold, relative to control, respectively. In plants treated with IAA, 7-chloro-3-methyl-8-quinolinecarboxylic acid, naphthalene acetic acid, 2-methoxy-3,6-dichlorobenzoic acid, and 4-amino-3,6,6-trichloropicolinic acid, levels of ethylene, ACC, and ABA increased in close correlation with inhibition of shoot growth. Aminoethoxyvinyl-glycine and cobalt ions, which inhibit ethylene synthesis, decreased ABA accumulation and growth inhibition, whereas the ethylene-releasing ethephon promoted ABA levels and growth inhibition. In accordance, tomato mutants defective in ethylene perception (never ripe) did not produce the xanthoxal and ABA increases and growth inhibition induced by auxins in wild-type plants. This suggests that auxin-stimulated ethylene triggers ABA accumulation and the consequent growth inhibition. Reduced catabolism most probably did not contribute to ABA increase, as indicated by immunoanalyses of ABA degradation and conjugation products in shoot tissue and by pulse experiments with [3H]-ABA in cell suspensions of G. aparine. In contrast, studies using inhibitors of ABA biosynthesis (fluridone, naproxen, and tungstate), ABA

  5. Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

    SciTech Connect

    Wang, Wei Craig, Zelieann R. Basavarajappa, Mallikarjuna S. Gupta, Rupesh K. Flaws, Jodi A.

    2012-01-15

    Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer that has been shown to inhibit growth of mouse antral follicles, however, little is known about the mechanisms by which DEHP does so. Oxidative stress has been linked to follicle growth inhibition as well as phthalate-induced toxicity in non-ovarian tissues. Thus, we hypothesized that DEHP causes oxidative stress and that this leads to inhibition of the growth of antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice (age 31–35 days) were cultured with vehicle control (dimethylsulfoxide [DMSO]) or DEHP (1–100 μg/ml) ± N-acetyl cysteine (NAC, an antioxidant at 0.25–1 mM). During culture, follicles were measured daily. At the end of culture, follicles were collected and processed for in vitro reactive oxygen species (ROS) assays to measure the presence of free radicals or for measurement of the expression and activity of various key antioxidant enzymes: Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX) and catalase (CAT). The results indicate that DEHP inhibits the growth of follicles compared to DMSO control and that NAC (0.25–1 mM) blocks the ability of DEHP to inhibit follicle growth. Furthermore, DEHP (10 μg/ml) significantly increases ROS levels and reduces the expression and activity of SOD1 compared to DMSO controls, whereas NAC (0.5 mM) rescues the effects of DEHP on ROS levels and SOD1. However, the expression and activity of GPX and CAT were not affected by DEHP treatment. Collectively, these data suggest that DEHP inhibits follicle growth by inducing production of ROS and by decreasing the expression and activity of SOD1. -- Highlights: ► DEHP inhibits growth and increases reactive oxygen species in ovarian antral follicles in vitro. ► NAC rescues the effects of DEHP on the growth and reactive oxygen species levels in follicles. ► DEHP decreases the expression and activity of Cu/Zn superoxide dismutase, which can be rescued by NAC, in antral

  6. Eupolyphaga sinensis walker displays inhibition on hepatocellular carcinoma through regulating cell growth and metastasis signaling.

    PubMed

    Zhang, Yanmin; Zhan, Yingzhuan; Zhang, Dongdong; Dai, Bingling; Ma, Weina; Qi, Junpeng; Liu, Rui; He, Langchong

    2014-01-01

    Tumor growth and metastasis are responsible for most cancer patients' deaths. Here, we report that eupolyphaga sinensis walker has an essential role in resisting hepatocellular carcinoma growth and metastasis. Compared with proliferation, colony formation, transwell assay and transplantable tumor in nude mouse in vitro and vivo, eupolyphaga sinensis walker extract (ESWE) showed good inhibition on the SMMC-7721 cell growth and metastasis. Using genome-wide microarray analysis, we found the down-regulated growth and metastasis factors, and selected down-regulated genes were confirmed by real-time PCR. Knockdown of a checkpoint PKCβ by siRNA significantly attenuated tumor inhibition and metastasis effects of ESWE. Moreover, our results indicate ESWE inhibits HCC growth by not only downregulating the signaling of PKCβ, Akt, m-TOR, Erk1/2, MEK-2, Raf and JNK-1, but also increasing cyclin D1 protein levels and decreasing amount of cyclin E, cyclin B1 and cdc2 of the cycle proteins. At the same time, ESWE reduced MMP2, MMP9 and CXCR4, PLG, NFκB and P53 activities. Overall, our studies demonstrate that ESWE is a key factor in growth and metastasis signaling inhibitor targeting the PKC, AKT, MAPK signaling and related metastasis signaling, having potential in cancer therapy. PMID:24980220

  7. Calcite crystal growth inhibition by humic substances with emphasis on hydrophobic acids from the Florida Everglades

    USGS Publications Warehouse

    Hoch, A.R.; Reddy, M.M.; Aiken, G.R.

    2000-01-01

    The crystallization of calcium carbonate minerals plays an integral role in the water chemistry of terrestrial ecosystems. Humic substances, which are ubiquitous in natural waters, have been shown to reduce or inhibit calcite crystal growth in experiments. The purpose of this study is to quantify and understand the kinetic effects of hydrophobic organic acids isolated from the Florida Everglades and a fulvic acid from Lake Fryxell, Antarctica, on the crystal growth of calcite (CaCO3). Highly reproducible calcite growth experiments were performed in a sealed reactor at constant pH, temperature, supersaturation (?? = 4.5), P(CO2) (10-3.5atm), and ionic strength (0.1 M) with various concentrations of organic acids. Higher plant-derived aquatic hydrophobic acids from the Everglades were more effective growth inhibitors than microbially derived fulvic acid from Lake Fryxell. Organic acid aromaticity correlated strongly with growth inhibition. Molecular weight and heteroatom content correlated well with growth inhibition, whereas carboxyl content and aliphatic nature did not. Copyright (C) 1999 Elsevier Science Ltd.

  8. Effect of Alexandrium tamarense on three bloom-forming algae

    NASA Astrophysics Data System (ADS)

    Yin, Juan; Xie, Jin; Yang, Weidong; Li, Hongye; Liu, Jiesheng

    2010-07-01

    We investigated the allelopathic properties of Alexandrium tamarense (Laboar) Balech on the growth of Prorocentrum donghaiense Lu, Chattonella marina (Subrahmanyan) Hara et Chihara and Heterosigma akashiwo (Hada) Hada in a laboratory experiment. We examined the growth of A. tamarense, C. marina, P. donghaiense and H. Akashiwo in co-cultures and the effect of filtrates from A. tamarense cultures in various growth phases, on the three harmful algal bloom (HAB)-forming algae. In co-cultures with A. tamarense, both C. marina and H. akashiwo were dramatically suppressed at high cell densities; in contrast, the growth of P. donghaiense varied in different inoculative ratios of A. tamarense and P. donghaiense. When the ratio was 1:1 ( P. donghaiense: A. tamarense), growth of P. donghaiense was inhibited considerably, while the growth of P. donghaiense was almost the same as that of the control when the ratio was 9:1. The growth difference of P. donghaiense, C. marina and H. akashiwo when co-cultured with A. tamarense indicated that the allelopathic effect may be one of the important factors in algal competition and phytoplankton succession involving A. tamarense. In addition, the filtrate from A. tamarense culture had negative impacts on these three HAB algae, and such inhibition varied with different growth phases of A. tamarense in parallel with reported values of PSP toxin content in Alexandrium cells. This implied that PSP toxin was possibly involved in allelopathy of A. tamarense. However, the rapid decomposition and inactivation of PSP toxin above pH 7 weakened this possibility. Further studies on the allelochemicals responsible for the allelopathy of A. tamarense need to be carried out in future.

  9. In vivo inhibition of polyamine biosynthesis and growth in tobacco ovary tissues

    NASA Technical Reports Server (NTRS)

    Slocum, R. D.; Galston, A. W.

    1985-01-01

    Post fertilization growth of tobacco ovary tissues treated with inhibitors of polyamine (PA) biosynthesis was examined in relation to endogenous PA titers and the activities of arginine decarboxylase (ADC, EC 4.1.1.19) and ornithine decarboxylase (ODC, EC 4.1.1.17). DL-alpha-Difluoromethylornithine (DFMO) and DL-alpha-difluoromethylarginine (DFMA), specific, irreversible ("suicide") inhibitors of ODC and ADC in vitro, were used to modulate PA biosynthesis in excised flowers. ODC represented >99% of the total decarboxylase activity in tobacco ovaries. In vivo inhibition of ODC with DFMO resulted in a significant decrease in PA titers, ovary fresh weight and protein content. Simultaneous inhibition of both decarboxylases by DFMO and DFMA produced only a marginally greater depression in growth and PA titers, indicating that ODC activity is rate-limiting for PA biosynthesis in these tissues. Paradoxically, DFMA alone inhibited PA biosynthesis, not as a result of a specific inhibition of ADC, but primarily through the inactivation of ODC. In vivo inhibition of ODC by DFMA appears to result from arginase-mediated hydrolysis of this inhibitor to urea and DFMO, the suicide substrate for ODC. Putrescine conjugates in tobacco appear to function as a storage form of this amine which, upon hydrolysis, may contribute to Put homeostasis during growth.

  10. Capsaicin Inhibits Preferentially the NADH Oxidase and Growth of Transformed Cells in Culture

    NASA Astrophysics Data System (ADS)

    Morre, D. James; Chueh, Pin-Ju; Morre, Dorothy M.

    1995-03-01

    A hormone- and growth factor-stimulated NADH oxidase of the mammalian plasma membrane, constitutively activated in transformed cells, was inhibited preferentially in HeLa, ovarian carcinoma, mammary adenocarcinoma, and HL-60 cells, all of human origin, by the naturally occurring quinone analog capsaicin (8-methyl-N-vanillyl-6-noneamide), compared with plasma membranes from human mammary epithelial, rat liver, normal rat kidney cells, or HL-60 cells induced to differentiate with dimethyl sulfoxide. With cells in culture, capsaicin preferentially inhibited growth of HeLa, ovarian carcinoma, mammary adenocarcinoma, and HL-60 cells but was largely without effect on the mammary epithelial cells, rat kidney cells, or HL-60 cells induced to differentiate with dimethyl sulfoxide. Inhibited cells became smaller and cell death was accompanied by a condensed and fragmented appearance of the nuclear DNA, as revealed by fluorescence microscopy with 4',6-diamidino-2-phenylindole, suggestive of apoptosis. The findings correlate capsaicin inhibition of cell surface NADH oxidase activity and inhibition of growth that correlate with capsaicin-induced apoptosis.

  11. Targeting Platelet-Derived Growth Factor Receptor β(+) Scaffold Formation Inhibits Choroidal Neovascularization.

    PubMed

    Strittmatter, Karin; Pomeroy, Hayley; Marneros, Alexander G

    2016-07-01

    Neovascular age-related macular degeneration is among the most common causes of irreversible blindness and manifests with choroidal neovascularization (CNV). Anti-vascular endothelial growth factor-A therapies are only partially effective and their chronic administration may impair functions of the choriocapillaris and retina. Thus, novel therapeutic targets are needed urgently. We have observed in a laser-induced model of CNV that a platelet-derived growth factor receptor β positive (PDGFRβ(+)) scaffold is formed before infiltration of neovessels into this scaffold to form CNV lesions, and that this scaffold limits the extent of neovascularization. Based on these observations we hypothesized that ablation of proliferating PDGFRβ(+) cells to prevent the formation of this scaffold might inhibit CNV growth and present a novel therapeutic approach for neovascular age-related macular degeneration. To test this hypothesis we targeted proliferating PDGFRβ(+) cells through independent distinct approaches after laser injury: i) by using an inducible genetic model to inhibit specifically proliferating PDGFRβ(+) cells, ii) by treating mice with a neutralizing anti-PDGFRβ antibody, iii) by administering an anti-PDGF-AB/BB aptamer, and iv) by using small chemical inhibitor approaches. The results show that therapeutic targeting of proliferating PDGFRβ(+) cells potently inhibits the formation of the pericyte-like scaffold, with concomitant attenuation of CNV. Moreover, we show that early inhibition of PDGFRβ(+) cell proliferation before neovessel formation is sufficient to inhibit scaffold formation and neovascularization. PMID:27338108

  12. Inhibition of Mycoplasma pneumoniae growth by FDA-approved anticancer and antiviral nucleoside and nucleobase analogs

    PubMed Central

    2013-01-01

    Background Mycoplasma pneumoniae (Mpn) is a human pathogen that causes acute and chronic respiratory diseases and has been linked to many extrapulmonary diseases. Due to the lack of cell wall, Mpn is resistant to antibiotics targeting cell wall synthesis such as penicillin. During the last 10 years macrolide-resistant Mpn strains have been frequently reported in Asian countries and have been spreading to Europe and the United States. Therefore, new antibiotics are needed. In this study, 30 FDA-approved anticancer or antiviral drugs were screened for inhibitory effects on Mpn growth and selected analogs were further characterized by inhibition of target enzymes and metabolism of radiolabeled substrates. Results Sixteen drugs showed varying inhibitory effects and seven showed strong inhibition of Mpn growth. The anticancer drug 6-thioguanine had a MIC (minimum inhibitory concentration required to cause 90% of growth inhibition) value of 0.20 μg ml-1, whereas trifluorothymidine, gemcitabine and dipyridamole had MIC values of approximately 2 μg ml-1. In wild type Mpn culture the presence of 6-thioguanine and dipyridamole strongly inhibited the uptake and metabolism of hypoxanthine and guanine while gemcitabine inhibited the uptake and metabolism of all nucleobases and thymidine. Trifluorothymidine and 5-fluorodeoxyuridine, however, stimulated the uptake and incorporation of radiolabeled thymidine and this stimulation was due to induction of thymidine kinase activity. Furthermore, Mpn hypoxanthine guanine phosphoribosyl transferase (HPRT) was cloned, expressed, and characterized. The 6-thioguanine, but not other purine analogs, strongly inhibited HPRT, which may in part explain the observed growth inhibition. Trifluorothymidine and 5-fluorodeoxyuridine were shown to be good substrates and inhibitors for thymidine kinase from human and Mycoplasma sources. Conclusion We have shown that several anticancer and antiviral nucleoside and nucleobase analogs are potent

  13. The angiogenesis regulator vasohibin-1 inhibits ovarian cancer growth and peritoneal dissemination and prolongs host survival.

    PubMed

    Takahashi, Yoshifumi; Saga, Yasushi; Koyanagi, Takahiro; Takei, Yuji; Machida, Sizuo; Taneichi, Akiyo; Mizukami, Hiroaki; Sato, Yasufumi; Matsubara, Shigeki; Fujiwara, Hiroyuki

    2015-12-01

    Vasohibin-1 (VASH1) is expressed in vascular endothelial cells stimulated by several angiogenic growth factors and displays autocrine activity to regulate angiogenesis via a negative feedback mechanism. In this study, we investigated the effect of VASH1 on ovarian cancer progression using VASH1-expressing ovarian cancer cells in vitro and in vivo. The growth ability of ovarian cancer cells engineered to express the VASH1 gene remained unchanged in vitro. However, we showed that VASH1 secretion by tumor cells inhibited the growth of human umbilical vein endothelial cells. Further, animal experiments showed that VASH1 expression inhibited tumor angiogenesis and growth. In a murine model of peritoneal dissemination of ovarian cancer cells, VASH1 inhibited peritoneal dissemination and ascites, resulting in significantly prolonged survival in mice. This indicates that VASH1 exerts an antitumor effect on ovarian cancer by inhibiting angiogenesis in the tumor environment. These findings suggest that a novel therapy based on VASH1 could be a useful therapeutic strategy for ovarian cancer. PMID:26460696

  14. DIETARY ISOTHIOCYANATE IBERIN INHIBITS GROWTH AND INDUCES APOPTOSIS IN HUMAN GLIOBLASTOMA CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, we evaluated the antiproliferative and proapoptotic effects of the isothiocyanate iberin, a bioactive agent in Brassicaceae species, in human glioblastoma cells. The human glioblastoma cell cultures were treated with different concentrations of iberin and tested for growth inhibition...

  15. Methylselenol, a selenium metabolite, inhibits colon cancer cell growth in vitro and in vivo

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Methylselenol is hypothesized to be a critical selenium (Se) metabolite for anticancer activity. Submicromolar methylselenol exposure inhibited cell growth and led to an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, and an induction of apoptosis in cancerous colon HCT11...

  16. Ionene polymers for selectively inhibiting the vitro growth of malignant cells

    NASA Technical Reports Server (NTRS)

    Rembaum, Alan (Inventor)

    1977-01-01

    Ionene polymers of the structure ##STR1## WHERE X AND Y ARE INTEGERS FROM 3 TO 16, Z.sup.- is an anion such as a halogen and n is an integer from 50 to 150 are found to bind negatively charged mammalian cells such as malignant cells and can be utilized to selectively inhibit the growth of malignant cells in vitro.

  17. The angiogenesis regulator vasohibin-1 inhibits ovarian cancer growth and peritoneal dissemination and prolongs host survival

    PubMed Central

    TAKAHASHI, YOSHIFUMI; SAGA, YASUSHI; KOYANAGI, TAKAHIRO; TAKEI, YUJI; MACHIDA, SIZUO; TANEICHI, AKIYO; MIZUKAMI, HIROAKI; SATO, YASUFUMI; MATSUBARA, SHIGEKI; FUJIWARA, HIROYUKI

    2015-01-01

    Vasohibin-1 (VASH1) is expressed in vascular endothelial cells stimulated by several angiogenic growth factors and displays autocrine activity to regulate angiogenesis via a negative feedback mechanism. In this study, we investigated the effect of VASH1 on ovarian cancer progression using VASH1-expressing ovarian cancer cells in vitro and in vivo. The growth ability of ovarian cancer cells engineered to express the VASH1 gene remained unchanged in vitro. However, we showed that VASH1 secretion by tumor cells inhibited the growth of human umbilical vein endothelial cells. Further, animal experiments showed that VASH1 expression inhibited tumor angiogenesis and growth. In a murine model of peritoneal dissemination of ovarian cancer cells, VASH1 inhibited peritoneal dissemination and ascites, resulting in significantly prolonged survival in mice. This indicates that VASH1 exerts an antitumor effect on ovarian cancer by inhibiting angiogenesis in the tumor environment. These findings suggest that a novel therapy based on VASH1 could be a useful therapeutic strategy for ovarian cancer. PMID:26460696

  18. Inhibition of histone deacetylase 6 activity reduces cyst growth in polycystic kidney disease.

    PubMed

    Cebotaru, Liudmila; Liu, Qiangni; Yanda, Murali K; Boinot, Clement; Outeda, Patricia; Huso, David L; Watnick, Terry; Guggino, William B; Cebotaru, Valeriu

    2016-07-01

    Abnormal proliferation of cyst-lining epithelium and increased intracystic fluid secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) are thought to contribute to cyst growth in autosomal dominant polycystic kidney disease (ADPKD). Histone deacetylase 6 (HDAC6) expression and activity are increased in certain cancers, neurodegenerative diseases, and in Pkd1-mutant renal epithelial cells. Inhibition of HDAC6 activity with specific inhibitors slows cancer growth. Here we studied the effect of tubacin, a specific HDAC6 inhibitor, on cyst growth in polycystic kidney disease. Treatment with tubacin prevented cyst formation in MDCK cells, an in vitro model of cystogenesis. Cyclic AMP stimulates cell proliferation and activates intracystic CFTR-mediated chloride secretion in ADPKD. Treatment with tubacin downregulated cyclic AMP levels, inhibited cell proliferation, and inhibited cyclic AMP-activated CFTR chloride currents in MDCK cells. We also found that tubacin reduced cyst growth by inhibiting proliferation of cyst-lining epithelial cells, downregulated cyclic AMP levels, and improved renal function in a Pkd1-conditional mouse model of ADPKD. Thus, HDAC6 could play a role in cyst formation and could serve as a potential therapeutic target in ADPKD. PMID:27165822

  19. A new diatom growth inhibition assay using the XTT colorimetric method.

    PubMed

    Jiang, Weina; Akagi, Takuya; Suzuki, Hidekazu; Takimoto, Ayaka; Nagai, Hiroshi

    2016-01-01

    Marine biofouling, which leads to significant operational stress and economic damage on marine infrastructures, is a major problem in marine related industries. Currently, the most common way to avoid marine biofouling involves the use of biocidal products in surface coatings. However, the need for environmentally friendly antibiofouling compounds has increased rapidly with the recent global prohibition of harmful antifoulants, such as tributyltin (TBT). In particular, periphytic diatoms have been shown to contribute significantly to biofilms, which play an important role in biofouling. Therefore, inhibiting the proliferation of fouling diatoms is a very important step in the prevention of marine biofouling. In this study, we developed a new, rapid, accurate, and convenient growth inhibition assay using the XTT colorimetric method to prevent the growth of the fouling periphytic diatom, Nitzschia amabilis Hidek. Suzuki (replaced synonym, Nitzschia laevis Hustedt). The feasibility of this method was verified by determining the growth inhibition activities of two standard photosynthetic inhibitors, DCMU and CuSO4. However, neither inhibitor had any cytotoxic activities at the range of concentrations tested. Moreover, this method was applied by screening and purification of herbicidic but non-cytotoxic compounds from cyanobacteria extracts. Our results demonstrate the utility of this newly established growth inhibition assay for the identification of marine anti-biofouling compounds. PMID:26945522

  20. Salinomycin inhibits prostate cancer growth and migration via induction of oxidative stress

    PubMed Central

    Ketola, K; Hilvo, M; Hyötyläinen, T; Vuoristo, A; Ruskeepää, A-L; Orešič, M; Kallioniemi, O; Iljin, K

    2012-01-01

    Background: We have shown that a sodium ionophore monensin inhibits prostate cancer cell growth. A structurally related compound to monensin, salinomycin, was recently identified as a putative cancer stem cell inhibitor. Methods: The growth inhibitory potential of salinomycin was studied in a panel of prostate cells. To get insights into the mechanism of action, a variety of assays such as gene expression and steroid profiling were performed in salinomycin-exposed prostate cancer cells. Results: Salinomycin inhibited the growth of prostate cancer cells, but did not affect non-malignant prostate epithelial cells. Salinomycin impacted on prostate cancer stem cell functions as evidenced by reduced aldehyde dehydrogenase activity and the fraction of CD44+ cells. Moreover, salinomycin reduced the expression of MYC, AR and ERG, induced oxidative stress as well as inhibited nuclear factor-κB activity and cell migration. Furthermore, profiling steroid metabolites revealed increased levels of oxidative stress-inducing steroids 7-ketocholesterol and aldosterone and decreased levels of antioxidative steroids progesterone and pregnenolone in salinomycin-exposed prostate cancer cells. Conclusion: Our results indicate that salinomycin inhibits prostate cancer cell growth and migration by reducing the expression of key prostate cancer oncogenes, inducing oxidative stress, decreasing the antioxidative capacity and cancer stem cell fraction. PMID:22215106

  1. mTOR inhibition improves fibroblast growth factor receptor targeting in hepatocellular carcinoma

    PubMed Central

    Scheller, T; Hellerbrand, C; Moser, C; Schmidt, K; Kroemer, A; Brunner, S M; Schlitt, H J; Geissler, E K; Lang, S A

    2015-01-01

    Background: Systemic therapy has proven only marginal effects in hepatocellular carcinoma (HCC) so far. The aim of this study was to evaluate the effect of targeting fibroblast growth factor receptor (FGFR) on tumour and stromal cells in HCC models. Methods: Human and murine HCC cells, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), hepatic stellate cells (HSCs), human HCC samples, FGFR inhibitor BGJ398 and mammalian target of rapamycin (mTOR) inhibitor rapamycin were used. Effects on growth, motility, signalling and angiogenic markers were determined. In vivo subcutaneous and syngeneic orthotopic tumour models were used. Results: In tumour cells and ECs, targeting FGFR showed significant inhibitory effects on signalling and motility. Minor effects of FGFR inhibition were observed on VSMCs and HSCs, which were significantly enhanced by combining FGFR and mTOR blockade. In vivo daily (5 mg kg−1) treatment with BGJ398 led to a significant growth inhibition in subcutaneous tumour models, but only a combination of FGFR and mTOR blockade impaired tumour growth in the orthotopic model. This was paralleled by reduced tumour cell proliferation, vascularisation, pericytes and increased apoptosis. Conclusions: Targeting FGFR with BGJ398 affects tumour cells and ECs, whereas only a combination with mTOR inhibition impairs recruitment of VSMCs and HSCs. Therefore, this study provides evidence for combined FGFR/mTOR inhibition in HCC. PMID:25688743

  2. Myristica fragrans Suppresses Tumor Growth and Metabolism by Inhibiting Lactate Dehydrogenase A.

    PubMed

    Kim, Eun-Yeong; Choi, Hee-Jung; Park, Mi-Ju; Jung, Yeon-Seop; Lee, Syng-Ook; Kim, Keuk-Jun; Choi, Jung-Hye; Chung, Tae-Wook; Ha, Ki-Tae

    2016-01-01

    Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation, rather than by maintaining a comparatively low rate of tricarboxylic acid cycle, i.e., Warburg's effect. In the pathway, the pyruvate produced by glycolysis is converted to lactic acid by lactate dehydrogenase (LDH). Here, we demonstrated that water extracts from the seeds of Myristica fragrans Houtt. (MF) inhibit the in vitro enzymatic activity of LDH. MF effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Although the expression of LDH-A was not changed by MF, both lactate production and LDH activity were decreased in MF-treated cells under both normoxic and hypoxic conditions. In addition, intracellular ATP levels were also decreased by MF treatment, and the uptake of glucose was also reduced by MF treatment. Furthermore, the experiment on tumor growth in the in vivo mice model revealed that MF effectively reduced the growth of allotransplanted Lewis lung carcinoma cells. Taken together, these results suggest that MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. These results implicate MF as a potential candidate for development into a novel drug against cancer through inhibition of LDH activity. PMID:27430914

  3. Contact dependent growth inhibition of E. coli O157:H7 by EC869 CDI system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Contact Dependent Growth Inhibition (CDI) is a recently discovered mechanism that microorganisms use to compete in various microecosystems. CDI systems express large cell surface exposed CdiA proteins with potent antimicrobial peptide tips. Many CDI systems also contain additional down...

  4. Blue-green algae

    MedlinePlus

    ... Talk with your health provider.Medications that slow blood clotting (Anticoagulant / Antiplatelet drugs)Blue-green algae might slow blood clotting. Taking blue-green algae along with medications that ...

  5. Magnetic separation of algae

    DOEpatents

    Nath, Pulak; Twary, Scott N.

    2016-04-26

    Described herein are methods and systems for harvesting, collecting, separating and/or dewatering algae using iron based salts combined with a magnetic field gradient to separate algae from an aqueous solution.

  6. The in vitro biological effect of nerve growth factor is inhibited by synthetic peptides.

    PubMed Central

    Longo, F M; Vu, T K; Mobley, W C

    1990-01-01

    Nerve growth factor (NGF)1 is a neurotrophic polypeptide that acts via specific receptors to promote the survival and growth of neurons. To delineate the NGF domain(s) responsible for eliciting biological activity, we synthesized small peptides corresponding to three regions in NGF that are hydrophilic and highly conserved. Several peptides from mouse NGF region 26-40 inhibited the neurite-promoting effect of NGF on sensory neurons in vitro. Inhibition was sequence-specific and could be overcome by increasing the concentration of NGF. Moreover, peptide actions were specific for NGF-mediated events in that they failed to block the neurotrophic activity of ciliary neuronotrophic factor (CNTF) or phorbol 12-myristate 13-acetate (PMA). In spite of the inhibition of NGF activity, peptides did not affect the binding of radiolabeled NGF. These studies define one region of NGF that may be required for neurotrophic activity. Images PMID:2100197

  7. Positional Isomers of Aspirin Are Equally Potent in Inhibiting Colon Cancer Cell Growth: Differences in Mode of Cyclooxygenase Inhibition

    PubMed Central

    Kodela, Ravinder; Chattopadhyay, Mitali; Goswami, Satindra; Gan, Zong Yuan; Rao, Praveen P. N.; Nia, Kamran V.; Velázquez-Martínez, Carlos A.

    2013-01-01

    We compared the differential effects of positional isomers of acetylsalicylic acid (o-ASA, m-ASA, and p-ASA) on cyclooxygenase (COX) inhibition, gastric prostaglandin E2 (PGE2), malondialdehyde, tumor necrosis factor-alpha (TNF-α) levels, superoxide dismutase (SOD) activity, human adenocarcinoma colon cancer cell growth inhibition, cell proliferation, apoptosis, and cell-cycle progression. We also evaluated the gastric toxicity exerted by ASA isomers. All ASA isomers inhibit COX enzymes, but only the o-ASA exerted an irreversible inhibitory profile. We did not observe a significant difference between ASA isomers in their ability to decrease the in vivo synthesis of PGE2 and SOD activity. Furthermore, all isomers increased the levels of gastric and TNF-α when administered orally at equimolar doses. We observed a dose-dependent cell growth inhibitory effect; the order of potency was p-ASA > m-ASA ≈ o-ASA. There was a dose-dependent decrease in cell proliferation and an increase in apoptosis, with a concomitant Go/G1 arrest. The ulcerogenic profile of the three ASA isomers showed a significant difference between o-ASA (aspirin) and its two positional isomers when administered orally at equimolar doses (1 mmol/kg); the ulcer index (UI) for o-ASA indicated extensive mucosal injury (UI = 38), whereas m-ASA and p-ASA produced a significantly decreased toxic response (UI = 12 and 8, respectively) under the same experimental conditions. These results suggest that the three positional isomers of ASA exert practically the same biologic profile in vitro and in vivo but showed different safety profiles. The mechanism of gastric ulcer formation exerted by aspirin and its two isomers warrants a more detailed and thorough investigation. PMID:23349335

  8. Miocene Coralline algae

    SciTech Connect

    Bosence, D.W.J.

    1988-01-01

    The coralline algae (Order Corallinales) were sedimentologically and ecologically important during the Miocene, a period when they were particularly abundant. The many poorly described and illustrated species and the lack of quantitative data in coralline thalli make specific determinations particularly difficult, but some species are well known and widespread in the Tethyan area. The sedimentologic importance of the Miocene coralline algae is reflected in the abundance of in-situ coralline buildups, rhodoliths, and coralline debris facies at Malta and Spain; similar sequences are known throughout the Tethyan Miocene. In-situ buildups vary from leafy crustose biostromes to walled reefs with dense coralline crusts and branches. Growth forms are apparently related to hydraulic energy. Rhodoliths vary from leafy, crustose, and open-branched forms in muddy sediments to dense, crustose, and radial-branching forms in coarse grainstones. Rhodolith form and internal structure correlate closely with hydraulic energy. Coralline genera are conservative and, as such, are useful in paleoenvironmental analysis. Of particular interest are the restricted depth ranges of recent coralline genera. More research is needed on the sedimentology, paleoecology, and systematics of the Cenozoic corallines, as they have particular value in paleoenvironmental analysis.

  9. Modelling algae growth and dissolved oxygen in the Seine River downstream the Paris urban area: contribution of high frequency measurements

    NASA Astrophysics Data System (ADS)

    Vilmin, Lauriane; Escoffier, Nicolas; Groleau, Alexis; Poulin, Michel; Flipo, Nicolas

    2014-05-01

    Dissolved oxygen is a key variable in the hydro-ecological functioning of river systems. The accurate representation of the different biogeochemical processes affecting algal blooms and dissolved oxygen in the water column in hydro-ecological models is crucial for the use of these models as reliable management tools. This study focuses on the water quality of the Seine River along a 225 km stretch, from Paris to the Seine estuary. The study area is highly urbanized and located downstream France's largest agricultural area, and therefore receives large amounts of nutrients. During the last decades, nutrient inputs have been significantly reduced, especially with the implementation of new sewage water treatment technologies. Even though the frequency and the intensity of observed algal blooms have decreased, blooms were observed in 2011 and 2012. These blooms are generally followed by a period of high organic matter accumulation, leading to high mineralization fluxes and potential oxygen depletion. The hydrodynamics and the water quality of the Seine River are simulated for the 2011-2012 period with the distributed process-based hydro-ecological model ProSe (Even et al., 1998). The simulated chlorophyll a and dissolved oxygen concentrations are compared to high frequency measurements at the Bougival monitoring station (50 km downstream from Paris), which is part of the CarboSeine monitoring network. The high frequency continuous dataset allows calibrating of primary producers' physiological parameters. New growth parameters are defined for the diatom community. The blooms occur at the end of the winter period (march 2011 and march 2012) and the optimal temperature for diatom growth is calibrated at 10°C, based on an analysis of the physiological response of the diatom community. One of the main outcomes of the modelling exercise is that the precise identification of the constituting communities of algal blooms must be achieved prior to the modelling itself. With the

  10. Molecular Characterization of Babesia bovis M17 Leucine Aminopeptidase and Inhibition of Babesia Growth by Bestatin.

    PubMed

    Aboge, Gabriel Oluga; Cao, Shinuo; Terkawi, Mohamad Alaa; Masatani, Tatsunori; Goo, Younkyoung; AbouLaila, Mahmoud; Nishikawa, Yoshifumi; Igarashi, Ikuo; Suzuki, Hiroshi; Xuan, Xuenan

    2015-10-01

    The M17 leucine aminopeptidase (M17LAP) enzymes of the other apicomplexan parasites have been characterized and shown to be inhibited by bestatin. Though Babesia bovis also belongs to the apicomplexan group, it is not known whether its M17LAP could display similar biochemical properties as well as inhibition profile. To unravel this uncertainty, a B. bovis M17LAP (BbM17LAP) gene was expressed in Escherichia coli , and activity of the recombinant enzyme as well as its inhibition by bestatin were evaluated. The inhibitory effect of the compound on growths of B. bovis and Babesia gibsoni in vitro was also determined. The expression of the gene fused with glutathione S-transferase (GST) yielded approximately 81-kDa recombinant BbM17LAP (rBbM17LAP). On probing with mouse anti-rBbM17LAP serum, a green fluorescence was observed on the parasite cytosol on confocal laser microscopy, and a specific band greater than the predicted molecular mass was seen on Western blotting. The Km and Vmax values of the recombinant enzyme were 139.3 ± 30.25 and 64.83 ± 4.6 μM, respectively, while the Ki was 2210 ± 358 μM after the inhibition. Bestatin was a more potent inhibitor of the growth of B. bovis [IC50 (50% inhibition concentration) = 131.7 ± 51.43 μM] than B. gibsoni [IC50 = 460.8 ± 114.45 μM] in vitro. The modest inhibition of both the rBbM17LAP activity and Babesia parasites' growth in vitro suggests that this inhibition may involve the endogenous enzyme in live parasites. Therefore, BbM17LAP may be a target of bestatin, though more studies with other aminopeptidase inhibitors are required to confirm this. PMID:26057618

  11. Platelet-Derived Growth Factor-Receptor α Strongly Inhibits Melanoma Growth In Vitro and In Vivo1

    PubMed Central

    Faraone, Debora; Aguzzi, Maria Simona; Toietta, Gabriele; Facchiano, Angelo M; Facchiano, Francesco; Magenta, Alessandra; Martelli, Fabio; Truffa, Silvia; Cesareo, Eleonora; Ribatti, Domenico; Capogrossi, Maurizio C; Facchiano, Antonio

    2009-01-01

    Cutaneous melanoma is the most aggressive skin cancer; it is highly metastatic and responds poorly to current therapies. The expression of platelet-derived growth factor receptors (PDGF-Rs) is reported to be reduced in metastatic melanoma compared with benign nevi or normal skin; we then hypothesized that PDGF-Rα may control growth of melanoma cells. We show here that melanoma cells overexpressing PDGF-Rα respond to serum with a significantly lower proliferation compared with that of controls. Apoptosis, cell cycle arrest, pRb dephosphorylation, and DNA synthesis inhibition were also observed in cells overexpressing PDGF-Rα. Proliferation was rescued by PDGF-Rα inhibitors, allowing to exclude nonspecific toxic effects and indicating that PDGF-Rα mediates autocrine antiproliferation signals in melanoma cells. Accordingly, PDGF-Rα was found to mediate staurosporine cytotoxicity. A protein array-based analysis of the mitogen-activated protein kinase pathway revealed that melanoma cells overexpressing PDGF-Rα show a strong reduction of c-Jun phosphorylated in serine 63 and of protein phosphatase 2A/Bα and a marked increase of p38γ, mitogen-activated protein kinase kinase 3, and signal regulatory protein α1 protein expression. In a mouse model of primary melanoma growth, infection with the Ad-vector overexpressing PDGF-Rα reached a significant 70% inhibition of primary melanoma growth (P < .001) and a similar inhibition of tumor angiogenesis. All together, these data demonstrate that PDGF-Rα strongly impairs melanoma growth likely through autocrine mechanisms and indicate a novel endogenous mechanism involved in melanoma control. PMID:19649203

  12. Platelet-derived growth factor-receptor alpha strongly inhibits melanoma growth in vitro and in vivo.

    PubMed

    Faraone, Debora; Aguzzi, Maria Simona; Toietta, Gabriele; Facchiano, Angelo M; Facchiano, Francesco; Magenta, Alessandra; Martelli, Fabio; Truffa, Silvia; Cesareo, Eleonora; Ribatti, Domenico; Capogrossi, Maurizio C; Facchiano, Antonio

    2009-08-01

    Cutaneous melanoma is the most aggressive skin cancer; it is highly metastatic and responds poorly to current therapies. The expression of platelet-derived growth factor receptors (PDGF-Rs) is reported to be reduced in metastatic melanoma compared with benign nevi or normal skin; we then hypothesized that PDGF-Ralpha may control growth of melanoma cells. We show here that melanoma cells overexpressing PDGF-Ralpha respond to serum with a significantly lower proliferation compared with that of controls. Apoptosis, cell cycle arrest, pRb dephosphorylation, and DNA synthesis inhibition were also observed in cells overexpressing PDGF-Ralpha. Proliferation was rescued by PDGF-Ralpha inhibitors, allowing to exclude nonspecific toxic effects and indicating that PDGF-Ralpha mediates autocrine antiproliferation signals in melanoma cells. Accordingly, PDGF-Ralpha was found to mediate staurosporine cytotoxicity. A protein array-based analysis of the mitogen-activated protein kinase pathway revealed that melanoma cells overexpressing PDGF-Ralpha show a strong reduction of c-Jun phosphorylated in serine 63 and of protein phosphatase 2A/Balpha and a marked increase of p38gamma, mitogen-activated protein kinase kinase 3, and signal regulatory protein alpha1 protein expression. In a mouse model of primary melanoma growth, infection with the Ad-vector overexpressing PDGF-Ralpha reached a significant 70% inhibition of primary melanoma growth (P < .001) and a similar inhibition of tumor angiogenesis. All together, these data demonstrate that PDGF-Ralpha strongly impairs melanoma growth likely through autocrine mechanisms and indicate a novel endogenous mechanism involved in melanoma control. PMID:19649203

  13. Inhibition of Orobanche crenata seed germination and radicle growth by allelochemicals identified in cereals.

    PubMed

    Fernández-Aparicio, Mónica; Cimmino, Alessio; Evidente, Antonio; Rubiales, Diego

    2013-10-16

    Orobanche crenata is a parasitic weed that causes severe yield losses in important grain and forage legume crops. Cereals have been reported to inhibit O. crenata parasitism when grown intercropped with susceptible legumes, but the responsible metabolites have not been identified. A number of metabolites have been reported in cereals that have allelopathic properties against weeds, pests, and pathogens. We tested the effect of several allelochemicals identified in cereals on O. crenata seed germination and radicle development. We found that 2-benzoxazolinone, its derivative 6-chloroacetyl-2-benzoxazolinone, and scopoletin significantly inhibited O. crenata seed germination. Benzoxazolinones, l-tryptophan, and coumalic acid caused the stronger inhibition of radicle growth. Also, other metabolites reduced radicle length, this inhibition being dose-dependent. Only scopoletin caused cell necrotic-like darkening in the young radicles. Prospects for their application to parasitic weed management are discussed. PMID:24044614

  14. Pumpkin seed extract: Cell growth inhibition of hyperplastic and cancer cells, independent of steroid hormone receptors.

    PubMed

    Medjakovic, Svjetlana; Hobiger, Stefanie; Ardjomand-Woelkart, Karin; Bucar, Franz; Jungbauer, Alois

    2016-04-01

    Pumpkin seeds have been known in folk medicine as remedy for kidney, bladder and prostate disorders since centuries. Nevertheless, pumpkin research provides insufficient data to back up traditional beliefs of ethnomedical practice. The bioactivity of a hydro-ethanolic extract of pumpkin seeds from the Styrian pumpkin, Cucurbita pepo L. subsp. pepo var. styriaca, was investigated. As pumpkin seed extracts are standardized to cucurbitin, this compound was also tested. Transactivational activity was evaluated for human androgen receptor, estrogen receptor and progesterone receptor with in vitro yeast assays. Cell viability tests with prostate cancer cells, breast cancer cells, colorectal adenocarcinoma cells and a hyperplastic cell line from benign prostate hyperplasia tissue were performed. As model for non-hyperplastic cells, effects on cell viability were tested with a human dermal fibroblast cell line (HDF-5). No transactivational activity was found for human androgen receptor, estrogen receptor and progesterone receptor, for both, extract and cucurbitin. A cell growth inhibition of ~40-50% was observed for all cell lines, with the exception of HDF-5, which showed with ~20% much lower cell growth inhibition. Given the receptor status of some cell lines, a steroid-hormone receptor independent growth inhibiting effect can be assumed. The cell growth inhibition for fast growing cells together with the cell growth inhibition of prostate-, breast- and colon cancer cells corroborates the ethnomedical use of pumpkin seeds for a treatment of benign prostate hyperplasia. Moreover, due to the lack of androgenic activity, pumpkin seed applications can be regarded as safe for the prostate. PMID:26976217

  15. Induction of reactive oxygen species and algal growth inhibition by tritiated water with or without copper.

    PubMed

    Réty, C; Gilbin, R; Gomez, E

    2012-03-01

    Tritium ((3) H) is a radioactive element of ecological concern because of its release into aquatic ecosystems from nuclear power plants. However, the acute and chronic effects of tritiated water (HTO) on aquatic organisms are poorly documented, as are its effects on oxidative stress. In addition, the effects of HTO in combination with other contaminants remain largely unexamined. Herein, we document the effect of HTO on a primary aquatic producer (Chlamydomonas reinhardtii) by measuring growth and oxidative stress using fluorimetric (H(2) DCF-DA) determination of Reactive Oxygen Species (ROS) production. The maximum cell density of the alga (1.65 × 10(6) cells mL(-1) ) was reduced by 23% (1.27 × 10(6) cells mL(-1) ) at the highest exposure tested (59 MBq mL(-1) HTO), whereas cells exposed to 0.9 MBq mL(-1) showed a significantly enhanced maximum cell density of 1.90 × 10(6) cells mL(-1) , an increase of 15%. With regard to oxidative stress, exposure to HTO (0.04, 0.16, and 2.8 MBq mL(-1) ) induced an early dose-dependent peak in ROS production after 14-15 min of exposure, followed by a slow decrease in ROS which stabilized after 60 min. Moreover, this study showed that the presence of HTO may influence the impact of other conventional, nonradioactive contaminants, such as copper, a well known oxidizing trace metal for aquatic organisms. A significant synergic effect of copper and HTO on ROS production was observed. This synergic effect on oxidative stress was shown to be linked to an enhanced copper uptake rate measured in the presence of HTO (> 4 times). We conclude that HTO should be considered as a sensitizer when in a mixture with other contaminants, especially through interactions on the antioxidant system of algae. PMID:20607814

  16. Inhibition of Receptor Signaling and of Glioblastoma-derived Tumor Growth by a Novel PDGFRβ Aptamer

    PubMed Central

    Camorani, Simona; Esposito, Carla L; Rienzo, Anna; Catuogno, Silvia; Iaboni, Margherita; Condorelli, Gerolama; de Franciscis, Vittorio; Cerchia, Laura

    2014-01-01

    Platelet-derived growth factor receptor β (PDGFRβ) is a cell-surface tyrosine kinase receptor implicated in several cellular processes including proliferation, migration, and angiogenesis. It represents a compelling therapeutic target in many human tumors, including glioma. A number of tyrosine kinase inhibitors under development as antitumor agents have been found to inhibit PDGFRβ. However, they are not selective as they present multiple tyrosine kinase targets. Here, we report a novel PDGFRβ-specific antagonist represented by a nuclease-resistant RNA-aptamer, named Gint4.T. This aptamer is able to specifically bind to the human PDGFRβ ectodomain (Kd: 9.6 nmol/l) causing a strong inhibition of ligand-dependent receptor activation and of downstream signaling in cell lines and primary cultures of human glioblastoma cells. Moreover, Gint4.T aptamer drastically inhibits cell migration and proliferation, induces differentiation, and blocks tumor growth in vivo. In addition, Gint4.T aptamer prevents PDGFRβ heterodimerization with and resultant transactivation of epidermal growth factor receptor. As a result, the combination of Gint4.T and an epidermal growth factor receptor–targeted aptamer is better at slowing tumor growth than either single aptamer alone. These findings reveal Gint4.T as a PDGFRβ-drug candidate with translational potential. PMID:24566984

  17. Arctiin induces cell growth inhibition through the down-regulation of cyclin D1 expression.

    PubMed

    Matsuzaki, Youichirou; Koyama, Makoto; Hitomi, Toshiaki; Yokota, Tomoya; Kawanaka, Mayumi; Nishikawa, Akiyoshi; Germain, Doris; Sakai, Toshiyuki

    2008-03-01

    Arctiin is a major lignan constituent of Arctium lappa and has anti-cancer properties in animal models. It was recently reported that arctiin induces growth inhibition in human prostate cancer PC-3 cells. However, the growth inhibitory mechanism of arctiin remains unknown. Herein we report that arctiin induces growth inhibition and dephosphorylates the tumor-suppressor retinoblastoma protein in human immortalized keratinocyte HaCaT cells. We also show that the growth inhibition caused by arctiin is associated with the down-regulation of cyclin D1 protein expression. Furthermore, the arctiin-induced suppression of cyclin D1 protein expression occurs in various types of human tumor cells, including osteosarcoma, lung, colorectal, cervical and breast cancer, melanoma, transformed renal cells and prostate cancer. Depletion of the cyclin D1 protein using small interfering RNA-rendered human breast cancer MCF-7 cells insensitive to the growth inhibitory effects of arctiin, implicates cyclin D1 as an important target of arctiin. Taken together, these results suggest that arctiin down-regulates cyclin D1 protein expression and that this at least partially contributes to the anti-proliferative effect of arctiin. PMID:18288407

  18. MazF-induced growth inhibition and persister generation in Escherichia coli.

    PubMed

    Tripathi, Arti; Dewan, Pooja C; Siddique, Shahbaz A; Varadarajan, Raghavan

    2014-02-14

    Toxin-antitoxin systems are ubiquitous in nature and present on the chromosomes of both bacteria and archaea. MazEF is a type II toxin-antitoxin system present on the chromosome of Escherichia coli and other bacteria. Whether MazEF is involved in programmed cell death or reversible growth inhibition and bacterial persistence is a matter of debate. In the present work the role of MazF in bacterial physiology was studied by using an inactive, active-site mutant of MazF, E24A, to activate WT MazF expression from its own promoter. The ectopic expression of E24A MazF in a strain containing WT mazEF resulted in reversible growth arrest. Normal growth resumed on inhibiting the expression of E24A MazF. MazF-mediated growth arrest resulted in an increase in survival of bacterial cells during antibiotic stress. This was studied by activation of mazEF either by overexpression of an inactive, active-site mutant or pre-exposure to a sublethal dose of antibiotic. The MazF-mediated persistence phenotype was found to be independent of RecA and dependent on the presence of the ClpP and Lon proteases. This study confirms the role of MazEF in reversible growth inhibition and persistence. PMID:24375411

  19. AtOPR3 specifically inhibits primary root growth in Arabidopsis under phosphate deficiency

    PubMed Central

    Zheng, Hongyan; Pan, Xiaoying; Deng, Yuxia; Wu, Huamao; Liu, Pei; Li, Xuexian

    2016-01-01

    The primary root plays essential roles in root development, nutrient absorption, and root architectural establishment. Primary root growth is generally suppressed by phosphate (P) deficiency in A. thaliana; however, the underlying molecular mechanisms are largely elusive to date. We found that AtOPR3 specifically inhibited primary root growth under P deficiency via suppressing root tip growth at the transcriptional level, revealing an important novel function of AtOPR3 in regulating primary root response to the nutrient stress. Importantly, AtOPR3 functioned to down-regulate primary root growth under P limitation mostly by its own, rather than depending on the Jasmonic acid signaling pathway. Further, AtOPR3 interacted with ethylene and gibberellin signaling pathways to regulate primary root growth upon P deficiency. In addition, the AtOPR3’s function in inhibiting primary root growth upon P limitation was also partially dependent on auxin polar transport. Together, our studies provide new insights into how AtOPR3, together with hormone signaling interactions, modulates primary root growth in coping with the environmental stress in Arabidopsis. PMID:27101793

  20. Primate mammary development. Effects of hypophysectomy, prolactin inhibition, and growth hormone administration.

    PubMed Central

    Kleinberg, D L; Niemann, W; Flamm, E; Cooper, P; Babitsky, G; Valensi, Q

    1985-01-01

    The pituitary gland has been found to be an important factor in mammary development in primates. Hypophysectomy in 12 sexually immature monkeys caused significant inhibition of estradiol (E2)-induced mammary growth and development. A histological index of mammary development in sexually immature hypophysectomized animals was lower (0.82) than in intact E2-treated controls (3.4; P less than 0.008). Hypophysectomy also inhibited growth of the mammary gland as judged by a size index. Despite the hypophysectomy, E2 stimulated some, albeit blunted, mammary growth and development, which may have been due to incomplete hypophysectomy. Selective inhibition of prolactin by ergot drugs in intact animals did not prevent full mammary development, suggesting that there may be pituitary mammogens other than prolactin, or that very low or unmeasurable concentrations of prolactin were sufficient to synergize with E2 to cause full acinar development. The mean histological index was 3.08 in E2-treated animals and 3.16 in animals treated with E2 plus pergolide. There was also no difference in the size of the glands. We evaluated the effect of growth hormone on mammary development by treating three hypophysectomized animals with pure 22,000 mol wt human growth hormone (hGH) (Genentech, Inc., South San Francisco, CA). We found that physiological or slightly supraphysiological concentrations of hGH in animals with unmeasurable prolactin were incapable of restoring the capacity of E2 to induce full mammary growth. These findings suggest that, if growth hormone is a mammary mitogen, that physiological concentrations are insufficient to synergize with E2 to induce full mammary growth or that other forms of hGH are mammogenic. Our studies suggest that the role of the pituitary gland in mammary mitogenesis in primates is more complicated than previously thought. They also raise the possibility that heretofore unidentified pituitary substances may be mammogenic. Images PMID:4008646

  1. Inhibition of growth of Zymomonas mobilis by model compounds found in lignocellulosic hydrolysates

    PubMed Central

    2013-01-01

    Background During the pretreatment of biomass feedstocks and subsequent conditioning prior to saccharification, many toxic compounds are produced or introduced which inhibit microbial growth and in many cases, production of ethanol. An understanding of the toxic effects of compounds found in hydrolysate is critical to improving sugar utilization and ethanol yields in the fermentation process. In this study, we established a useful tool for surveying hydrolysate toxicity by measuring growth rates in the presence of toxic compounds, and examined the effects of selected model inhibitors of aldehydes, organic and inorganic acids (along with various cations), and alcohols on growth of Zymomonas mobilis 8b (a ZM4 derivative) using glucose or xylose as the carbon source. Results Toxicity strongly correlated to hydrophobicity in Z. mobilis, which has been observed in Escherichia coli and Saccharomyces cerevisiae for aldehydes and with some exceptions, organic acids. We observed Z. mobilis 8b to be more tolerant to organic acids than previously reported, although the carbon source and growth conditions play a role in tolerance. Growth in xylose was profoundly inhibited by monocarboxylic organic acids compared to growth in glucose, whereas dicarboxylic acids demonstrated little or no effects on growth rate in either substrate. Furthermore, cations can be ranked in order of their toxicity, Ca++ > > Na+ > NH4+ > K+. HMF (5-hydroxymethylfurfural), furfural and acetate, which were observed to contribute to inhibition of Z. mobilis growth in dilute acid pretreated corn stover hydrolysate, do not interact in a synergistic manner in combination. We provide further evidence that Z. mobilis 8b is capable of converting the aldehydes furfural, vanillin, 4-hydroxybenzaldehyde and to some extent syringaldehyde to their alcohol forms (furfuryl, vanillyl, 4-hydroxybenzyl and syringyl alcohol) during fermentation. Conclusions Several key findings in this report provide a

  2. New tools for chloroplast genetic engineering allow the synthesis of human growth hormone in the green alga Chlamydomonas reinhardtii.

    PubMed

    Wannathong, Thanyanan; Waterhouse, Janet C; Young, Rosanna E B; Economou, Chloe K; Purton, Saul

    2016-06-01

    In recent years, there has been an increasing interest in the exploitation of microalgae in industrial biotechnology. Potentially, these phototrophic eukaryotes could be used for the low-cost synthesis of valuable recombinant products such as bioactive metabolites and therapeutic proteins. The algal chloroplast in particular represents an attractive target for such genetic engineering, both because it houses major metabolic pathways and because foreign genes can be targeted to specific loci within the chloroplast genome, resulting in high-level, stable expression. However, routine methods for chloroplast genetic engineering are currently available only for one species-Chlamydomonas reinhardtii-and even here, there are limitations to the existing technology, including the need for an expensive biolistic device for DNA delivery, the lack of robust expression vectors, and the undesirable use of antibiotic resistance markers. Here, we describe a new strain and vectors for targeted insertion of transgenes into a neutral chloroplast locus that (i) allow scar-less fusion of a transgenic coding sequence to the promoter/5'UTR element of the highly expressed endogenous genes psaA or atpA, (ii) employ the endogenous gene psbH as an effective but benign selectable marker, and (iii) ensure the successful integration of the transgene construct in all transformant lines. Transformation is achieved by a simple and cheap method of agitation of a DNA/cell suspension with glass beads, with selection based on the phototrophic rescue of a cell wall-deficient ΔpsbH strain. We demonstrate the utility of these tools in the creation of a transgenic line that produces high levels of functional human growth hormone. PMID:26887319

  3. Targeted blockade of JAK/STAT3 signaling inhibits ovarian carcinoma growth

    PubMed Central

    Gritsina, Galina; Xiao, Fang; O'Brien, Shane W.; Gabbasov, Rashid; Maglaty, Marisa A.; Xu, Ren-Huan; Thapa, Roshan J.; Zhou, Yan; Nicolas, Emmanuelle; Litwin, Samuel; Balachandran, Siddharth; Sigal, Luis J.; Huszar, Dennis; Connolly, Denise C.

    2015-01-01

    Ovarian carcinoma (OC) is the fifth leading cause of death among women in the United States. Persistent activation of signal transducer and activator of transcription (STAT3) is frequently detected in OC. STAT3 is activated by Janus family kinases (JAK) via cytokine receptors, growth factor receptor and non-growth factor receptor tyrosine kinases. Activation of STAT3 mediates tumor cell proliferation, survival, motility, invasion, and angiogenesis, and recent work demonstrates that STAT3 activation suppresses anti-tumor immune responses and supports tumor-promoting inflammation. We hypothesized that therapeutic targeting of the JAK/STAT3 pathway would inhibit tumor growth by direct effects on OC cells and by inhibition of cells in the tumor microenvironment (TME). To test this, we evaluated the effects of a small molecule JAK inhibitor, AZD1480, on cell viability, apoptosis, proliferation, migration and adhesion of OC cells in vitro. We then evaluated the effects of AZD1480 on in vivo tumor growth and progression, gene expression, tumor-associated matrix metalloproteinase (MMP) activity and immune cell populations in a transgenic mouse model of OC. AZD1480-treatment inhibited STAT3 phosphorylation and DNA binding, and migration and adhesion of cultured OC cells and ovarian tumor growth rate, volume and ascites production in mice. In addition, drug treatment led to altered gene expression, decreased tumor-associated MMP activity, and fewer suppressor T cells in the peritoneal tumor microenvironment of tumor-bearing mice than control mice. Taken together, our results show pharmacological inhibition of the JAK2/STAT3 pathway leads to disruption of functions essential for ovarian tumor growth and progression and represents a promising therapeutic strategy. PMID:25646015

  4. Targeted Blockade of JAK/STAT3 Signaling Inhibits Ovarian Carcinoma Growth.

    PubMed

    Gritsina, Galina; Xiao, Fang; O'Brien, Shane W; Gabbasov, Rashid; Maglaty, Marisa A; Xu, Ren-Huan; Thapa, Roshan J; Zhou, Yan; Nicolas, Emmanuelle; Litwin, Samuel; Balachandran, Siddharth; Sigal, Luis J; Huszar, Dennis; Connolly, Denise C

    2015-04-01

    Ovarian carcinoma is the fifth leading cause of death among women in the United States. Persistent activation of STAT3 is frequently detected in ovarian carcinoma. STAT3 is activated by Janus family kinases (JAK) via cytokine receptors, growth factor receptor, and non-growth factor receptor tyrosine kinases. Activation of STAT3 mediates tumor cell proliferation, survival, motility, invasion, and angiogenesis, and recent work demonstrates that STAT3 activation suppresses antitumor immune responses and supports tumor-promoting inflammation. We hypothesized that therapeutic targeting of the JAK/STAT3 pathway would inhibit tumor growth by direct effects on ovarian carcinoma cells and by inhibition of cells in the tumor microenvironment (TME). To test this, we evaluated the effects of a small-molecule JAK inhibitor, AZD1480, on cell viability, apoptosis, proliferation, migration, and adhesion of ovarian carcinoma cells in vitro. We then evaluated the effects of AZD1480 on in vivo tumor growth and progression, gene expression, tumor-associated matrix metalloproteinase (MMP) activity, and immune cell populations in a transgenic mouse model of ovarian carcinoma. AZD1480 treatment inhibited STAT3 phosphorylation and DNA binding, and migration and adhesion of cultured ovarian carcinoma cells and ovarian tumor growth rate, volume, and ascites production in mice. In addition, drug treatment led to altered gene expression, decreased tumor-associated MMP activity, and fewer suppressor T cells in the peritoneal TME of tumor-bearing mice than control mice. Taken together, our results show pharmacologic inhibition of the JAK2/STAT3 pathway leads to disruption of functions essential for ovarian tumor growth and progression and represents a promising therapeutic strategy. PMID:25646015

  5. Methoxychlor inhibits growth of antral follicles by altering cell cycle regulators

    SciTech Connect

    Gupta, Rupesh K. Meachum, Sharon Hernandez-Ochoa, Isabel Peretz, Jackye Yao, Humphrey H. Flaws, Jodi A.

    2009-10-01

    Methoxychlor (MXC) reduces fertility in female rodents, decreases antral follicle numbers, and increases atresia through oxidative stress pathways. MXC also inhibits antral follicle growth in vitro. The mechanism by which MXC inhibits growth of follicles is unknown. The growth of follicles is controlled, in part, by cell cycle regulators. Thus, we tested the hypothesis that MXC inhibits follicle growth by reducing the levels of selected cell cycle regulators. Further, we tested whether co-treatment with an antioxidant, N-acetyl cysteine (NAC), prevents the MXC-induced reduction in cell cycle regulators. For in vivo studies, adult cycling CD-1 mice were dosed with MXC or vehicle for 20 days. Treated ovaries were subjected to immunohistochemistry for proliferating cell nuclear antigen (PCNA) staining. For in vitro studies, antral follicles isolated from adult cycling CD-1 mouse ovaries were cultured with vehicle, MXC, and/or NAC for 48, 72 and 96 h. Levels of cyclin D2 (Ccnd2) and cyclin dependent kinase 4 (Cdk4) were measured using in vivo and in vitro samples. The results indicate that MXC decreased PCNA staining, and Ccnd2 and Cdk4 levels compared to controls. NAC co-treatment restored follicle growth and expression of Ccnd2 and Cdk4. Collectively, these data indicate that MXC exposure reduces the levels of Ccnd2 and Cdk4 in follicles, and that protection from oxidative stress restores Ccnd2 and Cdk4 levels. Therefore, MXC-induced oxidative stress may decrease the levels of cell cycle regulators, which in turn, results in inhibition of the growth of antral follicles.

  6. Direct inhibition of Retinoblastoma phosphorylation by Nimbolide causes cell cycle arrest and suppresses glioblastoma growth

    PubMed Central

    Anderson, Jane; Liu, Xiaona; Henry, Heather; Gasilina, Anjelika; Nassar, Nicholas; Ghosh, Jayeeta; Clark, Jason P; Kumar, Ashish; Pauletti, Giovanni M.; Ghosh, Pradip K; Dasgupta, Biplab

    2013-01-01

    Purpose Classical pharmacology allows the use and development of conventional phytomedicine faster and more economically than conventional drugs. This approach should be tested for their efficacy in terms of complementarity and disease control. The purpose of this study was to determine the molecular mechanisms by which nimbolide, a triterpenoid found in the well-known medicinal plant Azadirachta indica controls glioblastoma (GBM) growth. Experimental Design Using in vitro signaling, anchorage-independent growth, kinase assays, and xenograft models, we investigated the mechanisms of its growth inhibition in glioblastoma. Results We show that nimbolide or an ethanol soluble fraction of A. indica leaves (Azt) that contains nimbolide as the principal cytotoxic agent is highly cytotoxic against GBM in vitro and in vivo. Azt caused cell cycle arrest, most prominently at the G1-S stage in GBM cells expressing EGFRvIII, an oncogene present in about 20-25% of GBMs. Azt/nimbolide directly inhibited CDK4/CDK6 kinase activity leading to hypophosphorylation of the retinoblastoma (RB) protein, cell cycle arrest at G1-S and cell death. Independent of RB hypophosphorylation, Azt also significantly reduced proliferative and survival advantage of GBM cells in vitro and in tumor xenografts by downregulating Bcl2 and blocking growth factor induced phosphorylation of Akt, Erk1/2 and STAT3. These effects were specific since Azt did not affect mTOR or other cell cycle regulators. In vivo, Azt completely prevented initiation and inhibited progression of GBM growth. Conclusions Our preclinical findings demonstrate Nimbolide as a potent anti-glioma agent that blocks cell cycle and inhibits glioma growth in vitro and in vivo. PMID:24170547

  7. The Involvement of Gibberellins in 1,8-Cineole-Mediated Inhibition of Sprout Growth in Russet Burbank Tubers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The involvement of gibberellins in 1,8-cineole-mediated inhibition of tuber sprout growth was investigated in non-dormant field- and greenhouse-grown tubers of Russet Burbank. Continuous exposure of tubers to cineole in the vapor-phase resulted in a dose-dependent inhibition of sprout growth. Comp...

  8. Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice

    PubMed Central

    Huang, Tse-Hung; Chiu, Yi-Han; Chan, Yi-Lin; Chiu, Ya-Huang; Wang, Hang; Huang, Kuo-Chin; Li, Tsung-Lin; Hsu, Kuang-Hung; Wu, Chang-Jer

    2015-01-01

    Fucoidan, a heparin-like sulfated polysaccharide, is rich in brown algae. It has a wide assortment of protective activities against cancer, for example, induction of hepatocellular carcinoma senescence, induction of human breast and colon carcinoma apoptosis, and impediment of lung cancer cells migration and invasion. However, the anti-metastatic mechanism that fucoidan exploits remains elusive. In this report, we explored the effects of fucoidan on cachectic symptoms, tumor development, lung carcinoma cell spreading and proliferation, as well as expression of metastasis-associated proteins in the Lewis lung carcinoma (LLC) cells-inoculated mice model. We discovered that administration of fucoidan has prophylactic effects on mitigation of cachectic body weight loss and improvement of lung masses in tumor-inoculated mice. These desired effects are attributed to inhibition of LLC spreading and proliferation in lung tissues. Fucoidan also down-regulates expression of matrix metalloproteinases (MMPs), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and vascular endothelial growth factor (VEGF). Moreover, the tumor-bearing mice supplemented with fucoidan indeed benefit from an ensemble of the chemo-phylacticity. The fact is that fucoidan significantly decreases viability, migration, invasion, and MMPs activities of LLC cells. In summary, fucoidan is suitable to act as a chemo-preventative agent for minimizing cachectic symptoms as well as inhibiting lung carcinoma metastasis through down-regulating metastatic factors VEGF and MMPs. PMID:25854641

  9. Inhibition of Fusarium graminearum growth and mycotoxin production by phenolic extract from Spirulina sp.

    PubMed

    Pagnussatt, Fernanda Arnhold; Del Ponte, Emerson Medeiros; Garda-Buffon, Jaqueline; Badiale-Furlong, Eliana

    2014-01-01

    Fusarium graminearum is a fungal species complex pathogenic occurring worldwide, mainly associated with cereal crops. The most important Fusarium mycotoxins are fumonisins, zearalenone and trichothecenes. The availability of efficient control measures that are less harmful to both the environment and the consumers is urgent. For such, phenolic acids (PAs) from natural sources are known to reduce fungal contaminations. This work aimed to identify the PAs present in a culture extract of Spirulina algae (strain LEB-18) and evaluate its effect on mycelial growth rate, glucosamine level, amylase activity and mycotoxin production by four strains of two lineages of F. graminearum. Results showed that amendment of potato dextrose media with LEB-18 extract (3% w/v), which was mainly composed by gallic acid, greatly reduced radial growth of fungal colonies compared to media containing a single PA and the control. Also, average reductions of 40% and 62% in the glucosamine levels and the amylase activity were observed. In general, the LEB-18 extract and the PAs reduced mycotoxin concentration, with an average reduction of 68% for the trichothecene mycotoxins deoxynivalenol and nivalenol. PMID:24485311

  10. Caveolin-3 inhibits growth signal in cardiac myoblasts in a Ca2+-dependent manner

    PubMed Central

    Fujita, Takayuki; Otsu, Kouji; Oshikawa, Jin; Hori, Hideaki; Kitamura, Hitoshi; Ito, Takaaki; Umemura, Satoshi; Minamisawa, Susumu; Ishikawa, Yoshihiro

    2006-01-01

    Caveolin, a major protein component of caveolae, directly interacts with multiple signaling molecules, such as Ras and growth factor receptors, and inhibits their function. However, the role of the second messenger system in mediating this inhibition by caveolin remains poorly understood. We examined the role of Ca2+ -dependent signal in caveloin-mediated growth inhibition using a rat cardiac myoblast cell line (H9C2), in which the expression of caveolin-3, the muscle specific subtype, can be induced using the LacSwitch system. Upon induction with IPTG and serum-starvation, the expression of caveolin-3 was increased by 3.3-fold relative to that of mock-induced cells. The recombinant caveolin-3 was localized to the same subcellular fraction as endogenous caveolin-3 after sucrose gradient purification. Angiotensin II enhanced ERK phosphorylation, but this enhancement was significantly decreased in caveolin-3-induced cells in comparison to that in mock-induced cells. Similarly, when cells were stimulated with fetal calf serum, DNA synthesis, as determined by [3H]-thymidine incorporation, was significantly decreased in caveolin-3-induced cells. When cells were treated with Ca2+ chelator (BAPTA and EGTA), however, this attenuation was blunted. Calphostin (PKC inhibitor), but not cyclosporine A treatment (calcineurin inhibitor), blunted this attenuation in caveolin-3 induced cells. Our findings suggest that caveolin exhibits growth inhibition in a Ca2+-dependent manner, most likely through PKC, in cardiac myoblasts. PMID:16563233

  11. Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis.

    PubMed

    Huang, Yen-Chia; Huang, Fang-I; Mehndiratta, Samir; Lai, Ssu-Chia; Liou, Jing-Ping; Yang, Chia-Ron

    2015-07-30

    Histone deacetylases (HDACs) display multifaceted functions by coordinating the interaction of signal pathways with chromatin structure remodeling and the activation of non-histone proteins; these epigenetic regulations play an important role during malignancy progression. HDAC inhibition shows promise as a new strategy for cancer therapy; three HDAC inhibitors have been approved. We previously reported that N-hydroxy-3-{4-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide (MPT0G157), a novel indole-3-ethylsulfamoylphenylacrylamide compound, demonstrated potent HDAC inhibition and anti-inflammatory effects. In this study, we evaluated its anti-cancer activity in vitro and in vivo. MPT0G157 treatment significantly inhibited different tumor growth at submicromolar concentration and was particularly potent in human colorectal cancer (HCT116) cells. Apoptosis and inhibited HDACs activity induced by MPT0G157 was more potent than that by the marketed drugs PXD101 (Belinostat) and SAHA (Vorinostat). In an in vivo model, MPT0G157 markedly inhibited HCT116 xenograft tumor volume and reduced matrigel-induced angiogenesis. The anti-angiogenetic effect of MPT0G157 was found to increase the hyperacetylation of heat shock protein 90 (Hsp90) and promote hypoxia-inducible factor-1α (HIF-1α) degradation followed by down-regulation of vascular endothelial growth factor (VEGF) expression. Our results demonstrate that MPT0G157 has potential as a new drug candidate for cancer therapy. PMID:26087180

  12. Anticancer activity of MPT0G157, a derivative of indolylbenzenesulfonamide, inhibits tumor growth and angiogenesis

    PubMed Central

    Mehndiratta, Samir; Lai, Ssu-Chia; Liou, Jing-Ping; Yang, Chia-Ron

    2015-01-01

    Histone deacetylases (HDACs) display multifaceted functions by coordinating the interaction of signal pathways with chromatin structure remodeling and the activation of non-histone proteins; these epigenetic regulations play an important role during malignancy progression. HDAC inhibition shows promise as a new strategy for cancer therapy; three HDAC inhibitors have been approved. We previously reported that N-hydroxy-3-{4-[2-(2-methyl-1H-indol-3-yl)-ethylsulfamoyl]-phenyl}-acrylamide (MPT0G157), a novel indole-3-ethylsulfamoylphenylacrylamide compound, demonstrated potent HDAC inhibition and anti-inflammatory effects. In this study, we evaluated its anti-cancer activity in vitro and in vivo. MPT0G157 treatment significantly inhibited different tumor growth at submicromolar concentration and was particularly potent in human colorectal cancer (HCT116) cells. Apoptosis and inhibited HDACs activity induced by MPT0G157 was more potent than that by the marketed drugs PXD101 (Belinostat) and SAHA (Vorinostat). In an in vivo model, MPT0G157 markedly inhibited HCT116 xenograft tumor volume and reduced matrigel-induced angiogenesis. The anti-angiogenetic effect of MPT0G157 was found to increase the hyperacetylation of heat shock protein 90 (Hsp90) and promote hypoxia-inducible factor-1α (HIF-1α) degradation followed by down-regulation of vascular endothelial growth factor (VEGF) expression. Our results demonstrate that MPT0G157 has potential as a new drug candidate for cancer therapy. PMID:26087180

  13. Bromophenols from marine algae with potential anti-diabetic activities

    NASA Astrophysics Data System (ADS)

    Lin, Xiukun; Liu, Ming

    2012-12-01

    Marine algae contain various bromophenols with a variety of biological activities, including antimicrobial, anticancer, and anti-diabetic effects. Here, we briefly review the recent progress in researches on the biomaterials from marine algae, emphasizing the relationship between the structure and the potential anti-diabetic applications. Bromophenols from marine algae display their hyperglycemic effects by inhibiting the activities of protein tyrosine phosphatase 1B, α-glucosidase, as well as other mechanisms.

  14. Growth inhibition of foodborne pathogens and food spoilage organisms by select raw honeys.

    PubMed

    Mundo, Melissa A; Padilla-Zakour, Olga I; Worobo, Randy W

    2004-12-01

    Twenty-seven honey samples from different floral sources and geographical locations were evaluated for their ability to inhibit the growth of seven food spoilage organisms (Alcaligenes faecalis, Aspergillus niger, Bacillus stearothermophilus, Geotrichum candidum, Lactobacillus acidophilus, Penicillium expansum, Pseudomonas fluorescens) and five foodborne pathogens (Bacillus cereus, Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica Ser. Typhimurium, and Staphylococcus aureus) using an overlay inhibition assay. They were also tested for specific activity against S. aureus 9144 and B. stearothermophilus using the equivalent percent phenol test--a well diffusion assay corresponding to a dilute phenol standard curve. Honey inhibited bacterial growth due to high sugar concentration (reduced water activity), hydrogen peroxide generation, and proteinaceous compounds present in the honey. Some antibacterial activity was due to other unidentified components. The ability of honey to inhibit the growth of microorganisms varies widely, and could not be attributed to a specific floral source or demographic region produced in this study. Antibacterially active samples in this study included Montana buckwheat, tarweed, manuka, melaleuca, and saw palmetto. Furthermore, the bacteria were not uniformly affected by honey. Varying sensitivities to the antimicrobial properties were observed with four strains of S. aureus thus emphasizing the variability in the antibacterial effect of honey samples. Mold growth was not inhibited by any of the honeys tested. B. stearothermophilus, a heat-resistant spoilage bacteria, was shown to be highly sensitive to honey in both the overlay and well diffusion assays; other sensitive bacteria included A. faecalis and L. acidophilus. Non-peroxide antibacterial activity was observed in both assays; the highest instance was observed in the specific activity assay against B. stearothermophilus. Further research could indicate whether

  15. Simultaneous Assessment of Acidogenesis-Mitigation and Specific Bacterial Growth-Inhibition by Dentifrices.

    PubMed

    Forbes, Sarah; Latimer, Joe; Sreenivasan, Prem K; McBain, Andrew J

    2016-01-01

    Dentifrices can augment oral hygiene by inactivating bacteria and at sub-lethal concentrations may affect bacterial metabolism, potentially inhibiting acidogenesis, the main cause of caries. Reported herein is the development of a rapid method to simultaneously measure group-specific bactericidal and acidogenesis-mitigation effects of dentifrices on oral bacteria. Saliva was incubated aerobically and anaerobically in Tryptone Soya Broth, Wilkins-Chalgren Broth with mucin, or artificial saliva and was exposed to dentifrices containing triclosan/copolymer (TD); sodium fluoride (FD); stannous fluoride and zinc lactate (SFD1); or stannous fluoride, zinc lactate and stannous chloride (SFD2). Minimum inhibitory concentrations (MIC) were determined turbidometrically whilst group-specific minimum bactericidal concentrations (MBC) were assessed using growth media and conditions selective for total aerobes, total anaerobes, streptococci and Gram-negative anaerobes. Minimum acid neutralization concentration (MNC) was defined as the lowest concentration of dentifrice at which acidification was inhibited. Differences between MIC and MNC were calculated and normalized with respect to MIC to derive the combined inhibitory and neutralizing capacity (CINC), a cumulative measure of acidogenesis-mitigation and growth inhibition. The overall rank order for growth inhibition potency (MIC) under aerobic and anaerobic conditions was: TD> SFD2> SFD1> FD. Acidogenesis-mitigation (MNC) was ordered; TD> FD> SFD2> SFD1. CINC was ordered TD> FD> SFD2> SFD1 aerobically and TD> FD> SFD1> SFD2 anaerobically. With respect to group-specific bactericidal activity, TD generally exhibited the greatest potency, particularly against total aerobes, total anaerobes and streptococci. This approach enables the rapid simultaneous evaluation of acidity mitigation, growth inhibition and specific antimicrobial activity by dentifrices. PMID:26882309

  16. Simultaneous Assessment of Acidogenesis-Mitigation and Specific Bacterial Growth-Inhibition by Dentifrices

    PubMed Central

    Forbes, Sarah; Latimer, Joe; Sreenivasan, Prem K.; McBain, Andrew J.

    2016-01-01

    Dentifrices can augment oral hygiene by inactivating bacteria and at sub-lethal concentrations may affect bacterial metabolism, potentially inhibiting acidogenesis, the main cause of caries. Reported herein is the development of a rapid method to simultaneously measure group-specific bactericidal and acidogenesis-mitigation effects of dentifrices on oral bacteria. Saliva was incubated aerobically and anaerobically in Tryptone Soya Broth, Wilkins-Chalgren Broth with mucin, or artificial saliva and was exposed to dentifrices containing triclosan/copolymer (TD); sodium fluoride (FD); stannous fluoride and zinc lactate (SFD1); or stannous fluoride, zinc lactate and stannous chloride (SFD2). Minimum inhibitory concentrations (MIC) were determined turbidometrically whilst group-specific minimum bactericidal concentrations (MBC) were assessed using growth media and conditions selective for total aerobes, total anaerobes, streptococci and Gram-negative anaerobes. Minimum acid neutralization concentration (MNC) was defined as the lowest concentration of dentifrice at which acidification was inhibited. Differences between MIC and MNC were calculated and normalized with respect to MIC to derive the combined inhibitory and neutralizing capacity (CINC), a cumulative measure of acidogenesis-mitigation and growth inhibition. The overall rank order for growth inhibition potency (MIC) under aerobic and anaerobic conditions was: TD> SFD2> SFD1> FD. Acidogenesis-mitigation (MNC) was ordered; TD> FD> SFD2> SFD1. CINC was ordered TD> FD> SFD2> SFD1 aerobically and TD> FD> SFD1> SFD2 anaerobically. With respect to group-specific bactericidal activity, TD generally exhibited the greatest potency, particularly against total aerobes, total anaerobes and streptococci. This approach enables the rapid simultaneous evaluation of acidity mitigation, growth inhibition and specific antimicrobial activity by dentifrices. PMID:26882309

  17. Peptides of Matrix Gla Protein Inhibit Nucleation and Growth of Hydroxyapatite and Calcium Oxalate Monohydrate Crystals

    PubMed Central

    Goiko, Maria; Dierolf, Joshua; Gleberzon, Jared S.; Liao, Yinyin; Grohe, Bernd; Goldberg, Harvey A.; de Bruyn, John R.; Hunter, Graeme K.

    2013-01-01

    Matrix Gla protein (MGP) is a phosphorylated and γ-carboxylated protein that has been shown to prevent the deposition of hydroxyapatite crystals in the walls of blood vessels. MGP is also expressed in kidney and may inhibit the formation of kidney stones, which mainly consist of another crystalline phase, calcium oxalate monohydrate. To determine the mechanism by which MGP prevents soft-tissue calcification, we have synthesized peptides corresponding to the phosphorylated and γ-carboxylated sequences of human MGP in both post-translationally modified and non-modified forms. The effects of these peptides on hydroxyapatite formation and calcium oxalate crystallization were quantified using dynamic light scattering and scanning electron microscopy, respectively. Peptides YGlapS (MGP1-14: YγEpSHEpSMEpSYELNP), YEpS (YEpSHEpSMEpSYELNP), YGlaS (YγESHESMESYELNP) and SK-Gla (MGP43-56: SKPVHγELNRγEACDD) inhibited formation of hydroxyapatite in order of potency YGlapS > YEpS > YGlaS > SK-Gla. The effects of YGlapS, YEpS and YGlaS on hydroxyapatite formation were on both crystal nucleation and growth; the effect of SK-Gla was on nucleation. YGlapS and YEpS significantly inhibited the growth of calcium oxalate monohydrate crystals, while simultaneously promoting the formation of calcium oxalate dihydrate. The effects of these phosphopeptides on calcium oxalate monohydrate formation were on growth of crystals rather than nucleation. We have shown that the use of dynamic light scattering allows inhibitors of hydroxyapatite nucleation and growth to be distinguished. We have also demonstrated for the first time that MGP peptides inhibit the formation of calcium oxalate monohydrate. Based on the latter finding, we propose that MGP function not only to prevent blood-vessel calcification but also to inhibit stone formation in kidney. PMID:24265810

  18. A Mineral-Rich Red Algae Extract Inhibits Polyp Formation and Inflammation in the Gastrointestinal Tract of Mice on a High-Fat Diet

    PubMed Central

    Aslam, Muhammad Nadeem; Paruchuri, Tejaswi; Bhagavathula, Narasimharao; Varani, James

    2010-01-01

    The purpose of this study was to determine whether a mineral-rich extract derived from the red marine algae, Lithothamnion calcareum (Pallas), could be used as a dietary supplement for chemoprevention against colon polyp formation. Sixty C57bl/6 mice were divided into three groups based on diet. One group received a low-fat, rodent chow diet (AIN76A). The second group received a high-fat “Western style” diet (HFWD). The third group was fed the same HFWD with the mineral-rich extract included as a dietary supplement. Mice were maintained on the respective diets for 15 months. Autopsies were performed at the time of death or at the completion of the study. To summarize, the cumulative mortality rate was higher in mice on the HFWD during the 15 month period (55%) than in mice from the low-fat diet or the extract-supplemented high-fat diet groups (20% and 30%, respectively; p<0.05 with respect to both). Autopsies revealed colon polyps in 20% of the animals on the HFWD and none in animals of the other two groups (p<0.05). In addition to the grossly visible polyps, areas of hyperplasia in the colonic mucosa and inflammatory foci throughout the gastrointestinal tract were observed histologically in animals on the high-fat diet. Both were significantly reduced in animals on the low-fat diet and animals on the extract-supplemented HFWD. These data suggest that the mineral-rich algae extract may provide a novel approach to chemoprevention in the colon. PMID:20150219

  19. Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production

    PubMed Central

    Barton, Elisabeth R.; Park, SooHyun; James, Jose K.; Makarewich, Catherine A.; Philippou, Anastassios; Eletto, Davide; Lei, Hanqin; Brisson, Becky; Ostrovsky, Olga; Li, Zihai; Argon, Yair

    2012-01-01

    Insulin-like growth factors (IGFs) are critical for development and growth of skeletal muscles, but because several tissues produce IGFs, it is not clear which source is necessary or sufficient for muscle growth. Because it is critical for production of both IGF-I and IGF-II, we ablated glucose-regulated protein 94 (GRP94) in murine striated muscle to test the necessity of local IGFs for normal muscle growth. These mice exhibited smaller skeletal muscles with diminished IGF contents but with normal contractile function and no apparent endoplasmic reticulum stress response. This result shows that muscles rely on GRP94 primarily to support local production of IGFs, a pool that is necessary for normal muscle growth. In addition, body weights were ∼30% smaller than those of littermate controls, and circulating IGF-I also decreased significantly, yet glucose homeostasis was maintained with little disruption to the growth hormone pathway. The growth defect was complemented on administration of recombinant IGF-I. Thus, unlike liver production of IGF-I, muscle IGF-I is necessary not only locally but also globally for whole-body growth.—Barton, E. R., Park, S., James, J. K., Makarewich, C. A., Philippou, A., Eletto, D., Lei, H., Brisson, B., Ostrovsky, O., Li, Z., Argon, Y. Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production. PMID:22649033

  20. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis

    PubMed Central

    Zadra, Giorgia; Photopoulos, Cornelia; Tyekucheva, Svitlana; Heidari, Pedram; Weng, Qing Ping; Fedele, Giuseppe; Liu, Hong; Scaglia, Natalia; Priolo, Carmen; Sicinska, Ewa; Mahmood, Umar; Signoretti, Sabina; Birnberg, Neal; Loda, Massimo

    2014-01-01

    5′AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth remains to be determined. A small molecule screening was performed and identified MT 63–78, a specific and potent direct AMPK activator. Here, we show that direct activation of AMPK inhibits PCa cell growth in androgen sensitive and castration resistant PCa (CRPC) models, induces mitotic arrest, and apoptosis. In vivo, AMPK activation is sufficient to reduce PCa growth, whereas the allelic loss of its catalytic subunits fosters PCa development. Importantly, despite mTORC1 blockade, the suppression of de novo lipogenesis is the underpinning mechanism responsible for AMPK-mediated PCa growth inhibition, suggesting AMPK as a therapeutic target especially for lipogenesis-driven PCas. Finally, we demonstrate that MT 63–78 enhances the growth inhibitory effect of AR signaling inhibitors MDV3100 and abiraterone. This study thus provides a rationale for their combined use in CRPC treatment. PMID:24497570

  1. A recombinant decoy comprising EGFR and ErbB-4 inhibits tumor growth and metastasis

    PubMed Central

    Lindzen, Moshit; Carvalho, Silvia; Starr, Alex; Ben-Chetrit, Nir; Pradeep, Chaluvally-Raghavan; Köstler, Wolfgang J.; Rabinkov, Aaron; Lavi, Sara; Bacus, Sarah S.; Yarden, Yosef

    2011-01-01

    EGF-like growth factors control tumor progression, as well as evasion from the toxic effects of chemotherapy. Accordingly, antibodies targeting the cognate receptors, such as EGFR/ErbB-1 and the co-receptor HER2/ErbB-2, are widely used to treat cancer patients, but agents that target the EGF-like growth factors are not available. To circumvent the existence of 11 distinct ErbB ligands, we constructed a soluble fusion protein (hereinafter: TRAP-Fc) comprising truncated extracellular domains of EGFR/ErbB-1 and ErbB-4. The recombinant TRAP-Fc retained high affinity ligand binding to EGF-like growth factors and partially inhibited growth of a variety of cultured tumor cells. Consistently, TRAP-Fc displayed an inhibitory effect in xenograft models of human cancer, as well as synergy with chemotherapy. Additionally, TRAP-Fc inhibited invasive growth of mammary tumor cells and reduced their metastatic seeding in the lungs of animals. Taken together, the activities displayed by TRAP-Fc reinforce critical roles of EGF-like growth factors in tumor progression, and they warrant further tests of TRAP-Fc in pre-clinical models. PMID:22105361

  2. In vitro growth inhibition of human cancer cells by novel honokiol analogs.

    PubMed

    Lin, Jyh Ming; Prakasha Gowda, A S; Sharma, Arun K; Amin, Shantu

    2012-05-15

    Honokiol possesses many pharmacological activities including anti-cancer properties. Here in, we designed and synthesized honokiol analogs that block major honokiol metabolic pathway which may enhance their effectiveness. We studied their cytotoxicity in human cancer cells and evaluated possible mechanism of cell cycle arrest. Two analogs, namely 2 and 4, showed much higher growth inhibitory activity in A549 human lung cancer cells and significant increase of cell population in the G0-G1 phase. Further elucidation of the inhibition mechanism on cell cycle showed that analogs 2 and 4 inhibit both CDK1 and cyclin B1 protien levels in A549 cells. PMID:22533983

  3. Protein turnover and cellular autophagy in growing and growth-inhibited 3T3 cells

    SciTech Connect

    Papadopoulos, T.; Pfeifer, U. )

    1987-07-01

    The relationship between growth, protein degradation, and cellular autophagy was tested in growing and in growth-inhibited 3T3 cell monolayers. For the biochemical evaluation of DNA and protein metabolism, growth-inhibited 3T3 cell monolayers with high cell density and growing 3T3 cell monolayers with low cell density were labeled simultaneously with ({sup 14}C)thymidine and ({sup 3}H)leucine. The evaluation of the DNA turnover and additional ({sup 3}H)thymidine autoradiography showed that 24 to 5% of 3T3 cells continue to replicate even in the growth-inhibited state, where no accumulation of protein and DNA can be observed. Cell loss, therefore, has to be assumed to compensate for the ongoing cell proliferation. When the data of protein turnover were corrected for cell loss, it was found that the rate constant of protein synthesis in nongrowing monolayers was reduced to half the value found in growing monolayers. Simultaneously, the rate constant of protein degradation in nongrowing monolayers was increased to about 1.5-fold the value of growing monolayers. These data are in agreement with the assumption that cellular autophagy represents a major pathway of regulating protein degradation in 3T3 cells and that the regulation of autophagic protein degradation is of relevance for the transition from a growing to a nongrowing state.

  4. Piperine inhibits the growth and motility of triple-negative breast cancer cells.

    PubMed

    Greenshields, Anna L; Doucette, Carolyn D; Sutton, Kimberly M; Madera, Laurence; Annan, Henry; Yaffe, Paul B; Knickle, Allison F; Dong, Zhongmin; Hoskin, David W

    2015-02-01

    Piperine, an alkaloid from black pepper, is reported to have anticancer activities. In this study, we investigated the effect of piperine on the growth and motility of triple-negative breast cancer (TNBC) cells. Piperine inhibited the in vitro growth of TNBC cells, as well as hormone-dependent breast cancer cells, without affecting normal mammary epithelial cell growth. Exposure to piperine decreased the percentage of TNBC cells in the G2 phase of the cell cycle. In addition, G1- and G2-associated protein expression was decreased and p21(Waf1/Cip1) expression was increased in piperine-treated TNBC cells. Piperine also inhibited survival-promoting Akt activation in TNBC cells and caused caspase-dependent apoptosis via the mitochondrial pathway. Interestingly, combined treatment with piperine and γ radiation was more cytotoxic for TNBC cells than γ radiation alone. The in vitro migration of piperine-treated TNBC cells was impaired and expression of matrix metalloproteinase-2 and -9 mRNA was decreased, suggesting an antimetastatic effect by piperine. Finally, intratumoral administration of piperine inhibited the growth of TNBC xenografts in immune-deficient mice. Taken together, these findings suggest that piperine may be useful in the treatment of TNBC. PMID:25444919

  5. α-Tomatine inhibits growth and induces apoptosis in HL-60 human myeloid leukemia cells.

    PubMed

    Huang, Huarong; Chen, Shaohua; Van Doren, Jeremiah; Li, Dongli; Farichon, Chelsea; He, Yan; Zhang, Qiuyan; Zhang, Kun; Conney, Allan H; Goodin, Susan; Du, Zhiyun; Zheng, Xi

    2015-06-01

    α‑Tomatine is a glycoalkaloid that occurs naturally in tomatoes (Lycopersicon esculentum). In the present study, the effects of α‑tomatine on human myeloid leukemia HL‑60 cells were investigated. Treatment of HL‑60 cells with α‑tomatine resulted in growth inhibition and apoptosis in a concentration‑dependent manner. Tomatidine, the aglycone of tomatine had little effect on the growth and apoptosis of HL‑60 cells. Growth inhibition and apoptosis induced by α‑tomatine in HL‑60 cells was partially abrogated by addition of cholesterol indicating that interactions between α‑tomatine and cell membrane‑associated cholesterol may be important in mediating the effect of α‑tomatine. Activation of nuclear factor‑κB by the phorbol ester, 12‑O‑tetradecanoylphorbol‑13‑acetate failed to prevent apoptosis in HL‑60 cells treated with α‑tomatine. In animal experiments, it was found that treatment of mice with α‑tomatine inhibited the growth of HL‑60 xenografts in vivo. Results from the present study indicated that α‑tomatine may have useful anti‑leukemia activities. PMID:25625536

  6. A Flagellar Glycan-Specific Protein Encoded by Campylobacter Phages Inhibits Host Cell Growth

    PubMed Central

    Javed, Muhammad Afzal; Sacher, Jessica C.; van Alphen, Lieke B.; Patry, Robert T.; Szymanski, Christine M.

    2015-01-01

    We previously characterized a carbohydrate binding protein, Gp047, derived from lytic Campylobacter phage NCTC 12673, as a promising diagnostic tool for the identification of Campylobacter jejuni and Campylobacter coli. We also demonstrated that this protein binds specifically to acetamidino-modified pseudaminic acid residues on host flagella, but the role of this protein in the phage lifecycle remains unknown. Here, we report that Gp047 is capable of inhibiting C. jejuni growth both on solid and liquid media, an activity, which we found to be bacteriostatic. The Gp047 domain responsible for bacterial growth inhibition is localized to the C-terminal quarter of the protein, and this activity is both contact- and dose-dependent. Gp047 gene homologues are present in all Campylobacter phages sequenced to date, and the resulting protein is not part of the phage particle. Therefore, these results suggest that either phages of this pathogen have evolved an effector protein capable of host-specific growth inhibition, or that Campylobacter cells have developed a mechanism of regulating their growth upon sensing an impending phage threat. PMID:26694450

  7. TQ inhibits hepatocellular carcinoma growth in vitro and in vivo via repression of Notch signaling

    PubMed Central

    Ke, Xiquan; Zhao, Yan; Lu, Xinlan; Wang, Zhe; Liu, Yuanyuan; Ren, Mudan; Lu, Guifang; Zhang, Dan; Sun, Zhenguo; Xu, Zhipeng; Song, Jee Hoon; Cheng, Yulan; Meltzer, Stephen J.; He, Shuixiang

    2015-01-01

    Thymoquinone (TQ) has been reported to possess anti-tumor activity in various types of cancer. However, its effects and molecular mechanism of action in hepatocellular carcinoma (HCC) are still not completely understood. We observed that TQ inhibited tumor cell growth in vitro, where treatment with TQ arrested the cell cycle in G1 by upregulating p21 and downregulating cyclinD1 and CDK2 expression; moreover, TQ induced apoptosis by decreasing expression of Bcl-2 and increasing expression of Bax. Simultaneously, TQ demonstrated a suppressive impact on the Notch pathway, where overexpression of NICD1 reversed the inhibitory effect of TQ on cell proliferation, thereby attenuating the repressive effects of TQ on the Notch pathway, cyclinD1, CDK2 and Bcl-2, and also diminishing upregulation of p21 and Bax. In a xenograft model, TQ inhibited HCC growth in nude mice; this inhibitory effect in vivo, as well as of HCC cell growth in vitro, was associated with a discernible decline in NICD1 and Bcl-2 levels and a dramatic rise in p21 expression. In conclusion, TQ inhibits HCC cell growth by inducing cell cycle arrest and apoptosis, achieving these effects by repression of the Notch signaling pathway, suggesting that TQ represents a potential preventive or therapeutic agent in HCC patients. PMID:26416455

  8. Enhancer of zeste homolog 2 silencing inhibits tumor growth and lung metastasis in osteosarcoma

    PubMed Central

    Lv, Yang-Fan; Yan, Guang-Ning; Meng, Gang; Zhang, Xi; Guo, Qiao-Nan

    2015-01-01

    The enhancer of zeste homolog 2 (EZH2) methyltransferase is the catalytic subunit of polycomb repressive complex 2 (PRC2), which acts as a transcription repressor via the trimethylation of lysine 27 of histone 3 (H3K27me3). EZH2 has been recognised as an oncogene in several types of tumors; however, its role in osteosarcoma has not been fully elucidated. Herein, we show that EZH2 silencing inhibits tumor growth and lung metastasis in osteosarcoma by facilitating re-expression of the imprinting gene tumor-suppressing STF cDNA 3 (TSSC3). Our previous study showed that TSSC3 acts as a tumor suppressor in osteosarcoma. In this study, we found that EZH2 was abnormally elevated in osteosarcoma, and its overexpression was associated with poor prognosis in osteosarcoma. Silencing of EZH2 resulted in tumor growth inhibition, apoptosis and chemosensitivity enhancement. Moreover, suppression of EZH2 markedly inhibited tumor growth and lung metastasis in vivo. Furthermore, EZH2 knockdown facilitated the re-expression of TSSC3 by reducing H3K27me3 in the promoter region. Cotransfection with siEZH2 and siTSSC3 could partially reverse the ability of siEZH2 alone. We have demonstrated that EZH2 plays a crucial role in tumor growth and distant metastasis in osteosarcoma; its oncogenic role is related to its regulation of the expression of TSSC3. PMID:26265454

  9. Methyl anthranilate and γ-decalactone inhibit strawberry pathogen growth and achene Germination.

    PubMed

    Chambers, Alan H; Evans, Shane Alan; Folta, Kevin M

    2013-12-26

    Plant volatile compounds have been shown to affect microbial growth and seed germination. Here two fruity volatiles found in strawberry ( Fragaria × ananassa ), γ-decalactone ("peachlike" aroma) and methyl anthranilate ("grapelike" aroma), were tested for effects on relevant pathogens and seedling emergence. Significant growth reduction was observed for Botrytis cinerea , Colletotrichum gloeosporioides , Colletotrichum acutatum , Phomopsis obscurans , and Gnomonia fragariae at 1 mM γ-decalactone or methyl anthranilate, and 5 mM γ-decalactone or methyl anthranilate supplemented medium resulted in complete cessation of fungal growth. Phytophthora cactorum was especially sensitive to 1 mM γ-decalactone, showing complete growth inhibition. Bacteriostatic effects were observed in Xanthamonas cultures. Postharvest infestations on store-bought strawberries were inhibited with volatile treatment. The γ-decalactone volatile inhibited strawberry and Arabidopsis thaliana germination. These findings show that two compounds contributing to strawberry flavor may also contribute to shelf life and suggest that γ-decalactone may play an ecological role by preventing premature germination. PMID:24328200

  10. Struvite crystal growth inhibition by trisodium citrate and the formation of chemical complexes in growth solution

    NASA Astrophysics Data System (ADS)

    Prywer, Jolanta; Mielniczek-Brzóska, Ewa; Olszynski, Marcin

    2015-05-01

    Effect of trisodium citrate on the crystallization of struvite was studied. To evaluate such an effect an experiment of struvite growth from artificial urine was performed. The investigations are related to infectious urinary stones formation. The crystallization process was induced by the addition of aqueous ammonia solution to mimic the bacterial activity. The spectrophotometric results demonstrate that trisodium citrate increases induction time with respect to struvite formation and decreases the growth efficiency of struvite. The inhibitory effect of trisodium citrate on the nucleation and growth of struvite is explained in base of chemical speciation analysis. Such an analysis demonstrates that the inhibitory effect is related with the fact that trisodium citrate binds NH4 + and Mg2+ ions in the range of pH from 7 to 9.5 characteristic for struvite precipitation. The most important is the MgCit- complex whose concentration strongly depends on an increase in pH rather than on an increase in citrate concentrations.

  11. Feeding inhibition explains effects of imidacloprid on the growth, maturation, reproduction, and survival of Daphnia magna.

    PubMed

    Agatz, Annika; Cole, Tabatha A; Preuss, Thomas G; Zimmer, Elke; Brown, Colin D

    2013-03-19

    Effects of some xenobiotics on aquatic organisms might not be caused directly by the compound but rather arise from acclimation of the organism to stress invoked by feeding inhibition during exposure. Experiments were conducted to identify effects of imidacloprid on individual performance (feeding, growth, maturation, reproduction, and survival) of Daphnia magna under surplus and reduced food availability. Concentrations inhibiting feeding by 5, 50, and 95% after one day of exposure were 0.19, 1.83, and 8.70 mg/L, respectively. Exposure with imidacloprid at ≥ 3.7 mg/L reduced growth by up to 53 ± 11% within one week. Surplus food availability after inhibition allowed recovery from this growth inhibition, whereas limited food supply eliminated the potential for recovery in growth even for exposure at 0.15 mg/L. A shift in the distribution of individual energy reserves toward reproduction rather than growth resulted in increased reproduction after exposure to concentrations ≤ 0.4 mg/L. Exposure to imidacloprid at ≥ 4.0 mg/L overwhelmed this adaptive response and reduced reproduction by up to 57%. We used the individual based Daphnia magna population model IDamP as a virtual laboratory to demonstrate that only feeding was affected by imidacloprid, and that in turn this caused the other impacts on individual performance. Consideration of end points individually would have led to a different interpretation of the effects. Thus, we demonstrate how multiple lines of evidence linked by understanding the ecology of the organism are necessary to elucidate xenobiotic impacts along the effect cascade. PMID:23425205

  12. Genistein exposure inhibits growth and alters steroidogenesis in adult mouse antral follicles.

    PubMed

    Patel, Shreya; Peretz, Jackye; Pan, Yuan-Xiang; Helferich, William G; Flaws, Jodi A

    2016-02-15

    Genistein is a naturally occurring isoflavone phytoestrogen commonly found in plant products such as soybeans, lentils, and chickpeas. Genistein, like other phytoestrogens, has the potential to mimic, enhance, or impair the estradiol biosynthesis pathway, thereby potentially altering ovarian follicle growth. Previous studies have inconsistently indicated that genistein exposure may alter granulosa cell proliferation and hormone production, but no studies have examined the effects of genistein on intact antral follicles. Thus, this study was designed to test the hypothesis that genistein exposure inhibits follicle growth and steroidogenesis in intact antral follicles. To test this hypothesis, antral follicles isolated from CD-1 mice were cultured with vehicle (dimethyl sulfoxide; DMSO) or genistein (6.0 and 36μM) for 18-96h. Every 24h, follicle diameters were measured to assess growth. At the end of each culture period, the media were pooled to measure hormone levels, and the cultured follicles were collected to measure expression of cell cycle regulators and steroidogenic enzymes. The results indicate that genistein (36μM) inhibits growth of mouse antral follicles. Additionally, genistein (6.0 and 36μM) increases progesterone, testosterone, and dehydroepiandrosterone (DHEA) levels, but decreases estrone and estradiol levels. The results also indicate that genistein alters the expression of steroidogenic enzymes at 24, 72 and 96h, and the expression of cell cycle regulators at 18h. These data indicate that genistein exposure inhibits antral follicle growth by inhibiting the cell cycle, alters sex steroid hormone levels, and dysregulates steroidogenic enzymes in cultured mouse antral follicles. PMID:26792615

  13. MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA

    SciTech Connect

    Wang, Yihui; Tang, Qingchao; Li, Mingqi; Jiang, Shixiong; Wang, Xishan

    2014-02-07

    Highlights: • miR-375 is downregulated in colorectal cancer cell lines and tissues. • miR-375 inhibits colorectal cancer cell growth by targeting PIK3CA. • miR-375 inhibits colorectal cancer cell growth in xenograft nude mice model. - Abstract: Colorectal cancer (CRC) is the second most common cause of death from cancer. MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by triggering RNA degradation or interfering with translation. Aberrant miRNA expression is involved in human disease including cancer. Herein, we showed that miR-375 was frequently down-regulated in human colorectal cancer cell lines and tissues when compared to normal human colon tissues. PIK3CA was identified as a potential miR-375 target by bioinformatics. Overexpression of miR-375 in SW480 and HCT15 cells reduced PIK3CA protein expression. Subsequently, using reporter constructs, we showed that the PIK3CA untranslated region (3′-UTR) carries the directly binding site of miR-375. Additionally, miR-375 suppressed CRC cell proliferation and colony formation and led to cell cycle arrest. Furthermore, miR-375 overexpression resulted in inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. SiRNA-mediated silencing of PIK3CA blocked the inhibitory effect of miR-375 on CRC cell growth. Lastly, we found overexpressed miR-375 effectively repressed tumor growth in xenograft animal experiments. Taken together, we propose that overexpression of miR-375 may provide a selective growth inhibition for CRC cells by targeting PI3K/Akt signaling pathway.

  14. A cortical astrocyte subpopulation inhibits axon growth in vitro and in vivo.

    PubMed

    Liu, Rui; Wang, Zhe; Gou, Lin; Xu, Hanpeng

    2015-08-01

    Astrocytes are the most heterogeneous and predominant glial cell type in the central nervous system. However, the functional significance of this heterogeneity remains to be elucidated. Following injury, damaged astrocytes inhibit axonal regeneration in vivo and in vitro. Cultured primary astrocytes are commonly considered good supportive substrates for neuron attachment and axon regeneration. However, it is not known whether different populations of cells in the heterogeneous astrocyte culture affect neuron behavior in the same way. In the present study, the effect of astrocyte heterogeneity on neuronal attachment and neurite outgrowth was examined using an in vitro and in vivo coculture system. In vitro, neonatal cortical astrocytes were co-cultured with purified dorsal root ganglia (DRG) neurons and astrocyte growth morphology, neuron attachment and neurite growth were evaluated. The results demonstrated that the heterogeneous astrocyte cells showed two different types of growth pattern, typical and atypical. Typical astrocytes were supportive to neuron attachment and neurite growth, which was consistent with previous studies, whereas atypical astrocytes inhibited neuron attachment and neurite growth. These inhibitory astrocytes exhibited a special growth pattern with various shapes and sizes, a high cell density, few oligodendrocytes on the top layer and occupied a smaller growth area compared with typical astrocytes. Neurites extended freely on typical supportive astrocyte populations, however, moved away when they reached atypical astrocyte growth pattern. Neurons growing on the atypical astrocyte pattern demonstrated minimal neurite outgrowth and these neurites had a dystrophic appearance, however, neuronal survival was unaffected. Immunocytochemistry studies demonstrated that these atypical inhibitory astrocytes were glial fibrillary acidic protein (GFAP) positive cells. The existence of inhibitory astrocyte subpopulations in normal astrocytes reflects the

  15. Streptophyte algae and the origin of embryophytes

    PubMed Central

    Becker, Burkhard; Marin, Birger

    2009-01-01

    Background Land plants (embryophytes) evolved from streptophyte green algae, a small group of freshwater algae ranging from scaly, unicellular flagellates (Mesostigma) to complex, filamentous thalli with branching, cell differentiation and apical growth (Charales). Streptophyte algae and embryophytes form the division Streptophyta, whereas the remaining green algae are classified as Chlorophyta. The Charales (stoneworts) are often considered to be sister to land plants, suggesting progressive evolution towards cellular complexity within streptophyte green algae. Many cellular (e.g. phragmoplast, plasmodesmata, hexameric cellulose synthase, structure of flagellated cells, oogamous sexual reproduction with zygote retention) and physiological characters (e.g. type of photorespiration, phytochrome system) originated within streptophyte algae. Recent Progress Phylogenetic studies have demonstrated that Mesostigma (flagellate) and Chlorokybus (sarcinoid) form the earliest divergence within streptophytes, as sister to all other Streptophyta including embryophytes. The question whether Charales, Coleochaetales or Zygnematales are the sister to embryophytes is still (or, again) hotly debated. Projects to study genome evolution within streptophytes including protein families and polyadenylation signals have been initiated. In agreement with morphological and physiological features, many molecular traits believed to be specific for embryophytes have been shown to predate the Chlorophyta/Streptophyta split, or to have originated within streptophyte algae. Molecular phylogenies and the fossil record allow a detailed reconstruction of the early evolutionary events that led to the origin of true land plants, and shaped the current diversity and ecology of streptophyte green algae and their embryophyte descendants. Conclusions The Streptophyta/Chlorophyta divergence correlates with a remarkably conservative preference for freshwater/marine habitats, and the early freshwater

  16. Research on inhibitive behaviors of electrolysis on the growth of Microcystis aeruginosa.

    PubMed

    Xu, Y F; Yang, J; Ou, M M; Wang, Y L; Jia, J P; Pan, H D

    2006-06-01

    Electrochemical method using a novel Ti/RuO2 anode was employed to inhibit a typical cyanobacteria, Microcystis aeruginosa (M. aeruginosa) under different electrolytic conditions. It is demonstrated that Ti/RuO2 anode was more efficient than traditional graphite anode in M. aeruginosa inhibition. The experimental results showed that the higher current density or longer electrolytic time could effectively improve the inhibition of M. aeruginosa. In addition, sodium chloride was a more effective electrolyte than sodium sulfate to enhance inhibition. The maximum inhibiting rate dose to 100% could be obtained at a current density of 12 mA cm(-2) when sodium chloride was used as a supporting electrolyte. Furthermore, UV-Visible spectra demonstrated that the structures of phycocyanins and chlorophyll a (Chl a) in M. aeruginosa could be changed or destroyed during electrolysis. Moreover, EPR spectra showed the generation of the free radicals through electrolysis, which might be one of the reasons responsible for the inhibition of algal growth. PMID:16865923

  17. Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition

    PubMed Central

    Subramani, Ramadevi; Gonzalez, Elizabeth; Arumugam, Arunkumar; Nandy, Sushmita; Gonzalez, Viviana; Medel, Joshua; Camacho, Fernando; Ortega, Andrew; Bonkoungou, Sandrine; Narayan, Mahesh; Dwivedi, Alok kumar; Lakshmanaswamy, Rajkumar

    2016-01-01

    The mortality and morbidity rates of pancreatic cancer are high because of its extremely invasive and metastatic nature. Its lack of symptoms, late diagnosis and chemo–resistance and the ineffective treatment modalities warrant the development of new chemo–therapeutic agents for pancreatic cancer. Agents from medicinal plants have demonstrated therapeutic benefits in various human cancers. Nimbolide, an active molecule isolated from Azadirachta indica, has been reported to exhibit several medicinal properties. This study assessed the anticancer properties of nimbolide against pancreatic cancer. Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. Experiments with the autophagy inhibitors 3-methyladenine and chloroquine diphosphate salt and the apoptosis inhibitor z-VAD-fmk demonstrated that nimbolide-mediated ROS generation inhibited proliferation (through reduced PI3K/AKT/mTOR and ERK signaling) and metastasis (through decreased EMT, invasion, migration and colony forming abilities) via mitochondrial-mediated apoptotic cell death but not via autophagy. In vivo experiments also demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis. Overall, our data suggest that nimbolide can serve as a potential chemo–therapeutic agent for pancreatic cancer. PMID:26804739

  18. Nimbolide inhibits pancreatic cancer growth and metastasis through ROS-mediated apoptosis and inhibition of epithelial-to-mesenchymal transition.

    PubMed

    Subramani, Ramadevi; Gonzalez, Elizabeth; Arumugam, Arunkumar; Nandy, Sushmita; Gonzalez, Viviana; Medel, Joshua; Camacho, Fernando; Ortega, Andrew; Bonkoungou, Sandrine; Narayan, Mahesh; Dwivedi, Alok kumar; Lakshmanaswamy, Rajkumar

    2016-01-01

    The mortality and morbidity rates of pancreatic cancer are high because of its extremely invasive and metastatic nature. Its lack of symptoms, late diagnosis and chemo-resistance and the ineffective treatment modalities warrant the development of new chemo-therapeutic agents for pancreatic cancer. Agents from medicinal plants have demonstrated therapeutic benefits in various human cancers. Nimbolide, an active molecule isolated from Azadirachta indica, has been reported to exhibit several medicinal properties. This study assessed the anticancer properties of nimbolide against pancreatic cancer. Our data reveal that nimbolide induces excessive generation of reactive oxygen species (ROS), thereby regulating both apoptosis and autophagy in pancreatic cancer cells. Experiments with the autophagy inhibitors 3-methyladenine and chloroquine diphosphate salt and the apoptosis inhibitor z-VAD-fmk demonstrated that nimbolide-mediated ROS generation inhibited proliferation (through reduced PI3K/AKT/mTOR and ERK signaling) and metastasis (through decreased EMT, invasion, migration and colony forming abilities) via mitochondrial-mediated apoptotic cell death but not via autophagy. In vivo experiments also demonstrated that nimbolide was effective in inhibiting pancreatic cancer growth and metastasis. Overall, our data suggest that nimbolide can serve as a potential chemo-therapeutic agent for pancreatic cancer. PMID:26804739

  19. Insulin-like growth factor-binding protein-3 inhibition of prostate cancer growth involves suppression of angiogenesis.

    PubMed

    Liu, B; Lee, K-W; Anzo, M; Zhang, B; Zi, X; Tao, Y; Shiry, L; Pollak, M; Lin, S; Cohen, P

    2007-03-15

    Insulin-like growth factor-binding protein-3 (IGFBP-3) is a multifunctional protein that induces apoptosis utilizing both insulin-like growth factor receptor (IGF)-dependent and -independent mechanisms. We investigated the effects of IGFBP-3 on tumor growth and angiogenesis utilizing a human CaP xenograft model in severe-combined immunodeficiency mice. A 16-day course of IGFBP-3 injections reduced tumor size and increased apoptosis and also led to a reduction in the number of vessels stained with CD31. In vitro, IGFBP-3 inhibited both vascular endothelial growth factor- and IGF-stimulated human umbilical vein endothelial cells vascular network formation in a matrigel assay. This action is primarily IGF independent as shown by studies utilizing the non-IGFBP-binding IGF-1 analog Long-R3. Additionally, we used a fibroblast growth factor-enriched matrigel-plug assay and chick allantoic membrane assays to show that IGFBP-3 has potent antiangiogenic actions in vivo. Finally, overexpression of IGFBP-3 or the non-IGF-binding GGG-IGFBP-3 mutant in Zebrafish embryos confirmed that both IGFBP-3 and the non-IGF-binding mutant inhibited vessel formation in vivo, indicating that the antiangiogenic effect of IGFBP-3 is an IGF-independent phenomenon. Together, these studies provide the first evidence that IGFBP-3 has direct, IGF-independent inhibitory effects on angiogenesis providing an additional mechanism by which it exerts its tumor suppressive effects and further supporting its development for clinical use in the therapy of patients with prostate cancer. PMID:16983336

  20. Drugs Which Inhibit Osteoclast Function Suppress Tumor Growth through Calcium Reduction in Bone

    PubMed Central

    Li, Xin; Liao, Jinhui; Park, Serk In; Koh, Amy J; Sadler, William D; Pienta, Kenneth J; Rosol, Thomas J; McCauley, Laurie K

    2011-01-01

    Prostate carcinoma frequently metastasizes to bone where the microenvironment facilitates its growth. Inhibition of bone resorption is effective in reducing tumor burden and bone destruction in prostate cancer. However, whether drugs that inhibit osteoclast function inhibit tumor growth independent of inhibition of bone resorption is unclear. Calcium is released during bone resorption and the calcium sensing receptor is an important regulator of cancer cell proliferation. The goal of this investigation was to elucidate the role of calcium released during bone resorption and to determine the impact of drugs which suppress bone resorption on tumor growth in bone. To compare tumor growth in a skeletal versus non-skeletal site, equal numbers of canine prostate cancer cells expressing luciferase (ACE-1luc) prostate cancer cells were inoculated into a simple collagen matrix, neonatal mouse vertebrae (vossicles), human de-proteinized bone, or a mineralized collagen matrix. Implants were placed subcutaneously into athymic mice. Luciferase activity was used to track tumor growth weekly and at one month tumors were dissected for histologic analysis. Luciferase activity and tumor size were greater in vossicles, de-proteinized bone and mineralized collagen matrix versus non-mineralized collagen implants. The human osteoblastic prostate carcinoma cell line C4-2b also grew better in a mineral rich environment with a greater proliferation of C4-2b cells reflected by Ki-67 staining. Zoledronic acid (ZA), a bisphosphonate, and recombinant OPG-Fc, a RANKL inhibitor, were administered to mice bearing vertebral implants (vossicles) containing ACE-1 osteoblastic prostate cancer cells. Vossicles or collagen matrices were seeded with ACE-1luc cells subcutaneously in athymic mice (2 vossicles, 2 collagen implants/mouse). Mice received ZA (5μg/mouse, twice/week), (OPG-Fc at 10mg/kg, 3 times/week) or vehicle, and luciferase activity was measured weekly. Histologic analysis of the tumors

  1. Comparative toxicity of copper and acridine to fish, Daphnia and algae

    SciTech Connect

    Blaylock, B.G.; Frank, M.L.; McCarthy, J.F.

    1985-01-01

    A comparison was made of the sensitivity of fish, Daphnia and algae to the toxic effects of copper and acridine. A series of toxicity tests was conducted with these organisms, and the following biological endpoints determined: LC50s for fish, LC50s and effects on reproduction of Daphnia and 50% inhibition of the growth rate of algae. The 96-h LCO50s for bluegill (Lepomis macrochirus) and Daphnia magna exposed to copper were 2.2 and 0.13 mg/L, respectively. A chronic exposure to 0.03 mg/L of copper for 14 d significantly decreased reproduction in Daphnia. Exposure to 0.4 and 0.2 mg/L copper inhibited the growth rate of Selenastrum capricornutum and Chlorella vulgaris, respectively, by 50%. The 96-h LC50s for fathead minnows (Pimephales promelas) and D. magna exposed to acridine were 2.3 and 3.1 mg/L, respectively. A chronic exposure to 1.25 mg/L acridine for 14 d significantly inhibited reproduction in Daphnia, and an exposure to 0.9 mg/L inhibited the growth rate of S. capricornutum by 50%. Based on the biological endpoints determined in these tests, Daphnia were more sensitive to copper than were fish or algae. In contrast, the most sensitive biological endpoint in tests with acridine was the inhibition of algal growth. Comparison of these test results indicates that short-term toxicity tests used for screening toxicants for possible environmental effects should include both plant and animal species. 16 references, 4 figures, 4 tables.

  2. PYOMELANIN IS PRODUCED BY SHEWANELLA ALGAE BRY AND EFFECTED BY EXOGENOUS IRON

    SciTech Connect

    Turick, C; Frank Caccavo, F; Jr., J; Louis S. Tisa, L

    2006-11-29

    Melanin production by S. algae BrY occurred during late/post-exponential growth in lactate-basal-salts liquid medium supplemented with tyrosine or phenylalanine. The antioxidant ascorbate inhibited melanin production, but not production of the melanin precursor, homogentisic acid. In the absence of ascorbate, melanin production was inhibited by the 4-hydroxyplenylpyruvate dioxygenase inhibitor, sulcotrione and Fe(II) (>0.2mM). These data support the hypothesis that pigment production by S. algae BrY was a result the conversion of tyrosine or phenylalanine to homogentisic acid which was excreted, auto-oxidized and self-polymerized to form pyomelanin. The inverse relationship between Fe(II) concentration and pyomelanin production has implications that pyomelanin may play a role in iron assimilation under Fe(II) limiting conditions.

  3. When are antifreeze proteins in solution essential for ice growth inhibition?

    PubMed

    Drori, Ran; Davies, Peter L; Braslavsky, Ido

    2015-06-01

    Antifreeze proteins (AFPs) are a widespread class of proteins that bind to ice and facilitate the survival of organisms under freezing conditions. AFPs have enormous potential in applications that require control over ice growth. However, the nature of the binding interaction between AFPs and ice remains the subject of debate. Using a microfluidics system developed in-house we previously showed that hyperactive AFP from the Tenebrio molitor beetle, TmAFP, remains bound to an ice crystal surface after exchanging the solution surrounding the ice crystal to an AFP-free solution. Furthermore, these surface-adsorbed TmAFP molecules sufficed to prevent ice growth. These experiments provided compelling evidence for the irreversible binding of hyperactive AFPs to ice. Here, we tested a moderately active type III AFP (AFPIII) from a fish in a similar microfluidics system. We found, in solution exchange experiments that the AFPIIIs were also irreversibly bound to the ice crystals. However, some crystals displayed "burst" growth during the solution exchange. AFPIII, like other moderately active fish AFPs, is unable to bind to the basal plane of an ice crystal. We showed that although moderate AFPs bound to ice irreversibly, moderate AFPs in solution were needed to inhibit ice growth from the bipyramidal crystal tips. Instead of binding to the basal plane, these AFPs minimized the basal face size by stabilizing other crystal planes that converge to form the crystal tips. Furthermore, when access of solution to the basal plane was physically blocked by the microfluidics device walls, we observed enhancement of the antifreeze activity. These findings provide direct evidence that the weak point of ice growth inhibition by fish AFPs is the basal plane, whereas insect AFPs, which can bind to the basal plane, are able to inhibit its growth and thereby increase antifreeze activity. PMID:25946514

  4. Ginkgetin inhibits the growth of DU−145 prostate cancer cells through inhibition of signal transducer and activator of transcription 3 activity

    PubMed Central

    Jeon, Yoon Jung; Jung, Seung-Nam; Yun, Jieun; Lee, Chang Woo; Choi, Jiyeon; Lee, Yu-Jin; Han, Dong Cho; Kwon, Byoung-Mog

    2015-01-01

    Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in human cancers. Therefore, STAT3 is a therapeutic target of cancer drug discovery. We previously reported that natural products inhibited constitutively activated STAT3 in human prostate tumor cells. We used a dual-luciferase assay to screen 200 natural products isolated from herbal medicines and we identified ginkgetin obtained from the leaves of Ginkgo biloba L. as a STAT3 inhibitor. Ginkgetin inhibited both inducible and constitutively activated STAT3 and blocked the nuclear translocation of p-STAT3 in DU-145 prostate cancer cells. Furthermore, ginkgetin selectively inhibited the growth of prostate tumor cells stimulated with activated STAT3. Ginkgetin induced STAT3 dephosphorylation at Try705 and inhibited its localization to the nucleus, leading to the inhibition of expression of STAT3 target genes such as cell survival-related genes (cyclin D1 and survivin) and anti-apoptotic proteins (Bcl-2 and Bcl-xL). Therefore, ginkgetin inhibited the growth of STAT3-activated tumor cells. We also found that ginkgetin inhibited tumor growth in xenografted nude mice and downregulated p-STAT3Tyr705 and survivin in tumor tissues. This is the first report that ginkgetin exerts antitumor activity by inhibiting STAT3. Therefore, ginkgetin is a good STAT3 inhibitor and may be a useful lead molecule for development of a therapeutic STAT3 inhibitor. PMID:25611086

  5. The inhibition of crystal growth of mirabilite in aqueous solutions in the presence of phosphonates

    NASA Astrophysics Data System (ADS)

    Vavouraki, A. I.; Koutsoukos, P. G.

    2016-02-01

    The formation of sodium sulfate decahydrate (Mirabilite) has been known to cause serious damages to structural materials both of modern and of historical buildings. Methods which can retard or completely suppress the development of mirabilte crystals are urgently needed especially as remedies or preventive measures for the preservation of the built cultural heritage. In the present work we present results on the effect of the presence of phosphonate compounds on the kinetics of crystal growth from aqueous supersaturated solutions at 18 °C using the seeded growth technique. The phosphonate compounds tested differed with respect to the number of ionizable phosphonate groups and with respect to the number of amino groups in the respective molecules. The crystal growth process was monitored by the temperature changes during the exothermic crystallization of mirabilite in the stirred supersaturated solutions. The crystal growth of mirabilite in the presence of: (1-hydroxyethylidene)-1, 1-diphosphonic acid (HEDP), amino tri (methylene phosphonic acid) (ATMP), hexamethylenediaminetetra (methylene)phosphonic acid (HTDMP), and diethylene triamine penta(methylene phosphonic acid)(DETPMP) over a range of concentrations between 0.1-5% w/w resulted in significant decrease of the rates of mirabilite crystal growth. All phosphonic compounds tested reduced the crystallization rates up to 60% in comparison with additive-free solutions. The presence of the test compounds did not cause changes of the mechanism of crystal growth which was surface diffusion controlled, as shown by the second order dependence of the rates of mirabilite crystal growth on the relative supersaturation. The excellent fit of the measured rates to a kinetic Langmuir-type model suggested that the activity of the tested inhibitors could be attributed to the adsorption and subsequent reduction of the active crystal growth sites of the seed crystals. In all cases, the inhibitory activity was reduced with

  6. Small-molecule inhibition of PTPRZ reduces tumor growth in a rat model of glioblastoma

    PubMed Central

    Fujikawa, Akihiro; Nagahira, Asako; Sugawara, Hajime; Ishii, Kentaro; Imajo, Seiichi; Matsumoto, Masahito; Kuboyama, Kazuya; Suzuki, Ryoko; Tanga, Naomi; Noda, Masanori; Uchiyama, Susumu; Tomoo, Toshiyuki; Ogata, Atsuto; Masumura, Makoto; Noda, Masaharu

    2016-01-01

    Protein tyrosine phosphatase receptor-type Z (PTPRZ) is aberrantly over-expressed in glioblastoma and a causative factor for its malignancy. However, small molecules that selectively inhibit the catalytic activity of PTPRZ have not been discovered. We herein performed an in vitro screening of a chemical library, and identified SCB4380 as the first potent inhibitor for PTPRZ. The stoichiometric binding of SCB4380 to the catalytic pocket was demonstrated by biochemical and mass spectrometric analyses. We determined the crystal structure of the catalytic domain of PTPRZ, and the structural basis of the binding of SCB4380 elucidated by a molecular docking method was validated by site-directed mutagenesis studies. The intracellular delivery of SCB4380 by liposome carriers inhibited PTPRZ activity in C6 glioblastoma cells, and thereby suppressed their migration and proliferation in vitro and tumor growth in a rat allograft model. Therefore, selective inhibition of PTPRZ represents a promising approach for glioma therapy. PMID:26857455

  7. Cathepsin L knockdown enhances curcumin-mediated inhibition of growth, migration, and invasion of glioma cells.

    PubMed

    Fei, Yao; Xiong, Yajie; Zhao, Yifan; Wang, Wenjuan; Han, Meilin; Wang, Long; Tan, Caihong; Liang, Zhongqin

    2016-09-01

    Curcumin can be used to prevent and treat cancer. However, its exact underlying molecular mechanisms remain poorly understood. Cathepsin L, a lysosomal cysteine protease, is overexpressed in several cancer types. This study aimed to determine the role of cathepsin L in curcumin-mediated inhibition of growth, migration, and invasion of glioma cells. Results revealed that the activity of cathepsin L was enhanced in curcumin-treated glioma cells. Cathepsin L knockdown induced by RNA interference significantly promoted curcumin-induced cytotoxicity, apoptosis, and cell cycle arrest. The knockdown also inhibited the migration and invasion of glioma cells. Our results suggested that the inhibition of cathepsin L can enhance the sensitivity of glioma cells to curcumin. Therefore, cathepsin L may be a new target to enhance the efficacy of curcumin against cancers. PMID:27373979

  8. Cationic Pillararenes Potently Inhibit Biofilm Formation without Affecting Bacterial Growth and Viability.

    PubMed

    Joseph, Roymon; Naugolny, Alissa; Feldman, Mark; Herzog, Ido M; Fridman, Micha; Cohen, Yoram

    2016-01-27

    It is estimated that up to 80% of bacterial infections are accompanied by biofilm formation. Since bacteria in biofilms are less susceptible to antibiotics than are bacteria in the planktonic state, biofilm-associated infections pose a major health threat, and there is a pressing need for antibiofilm agents. Here we report that water-soluble cationic pillararenes differing in the quaternary ammonium groups efficiently inhibited the formation of biofilms by clinically important Gram-positive pathogens. Biofilm inhibition did not result from antimicrobial activity; thus, the compounds should not inhibit growth of natural bacterial flora. Moreover, none of the cationic pillararenes caused detectable membrane damage to red blood cells or toxicity to human cells in culture. The results indicate that cationic pillararenes have potential for use in medical applications in which biofilm formation is a problem. PMID:26745311

  9. Epidermal growth factor (EGF) inhibits stimulated thyroid hormone secretion in the mouse

    SciTech Connect

    Ahren, B.

    1987-07-01

    It is known that epidermal growth factor (EGF) inhibits iodide uptake in the thyroid follicular cells and lowers plasma levels of thyroid hormones upon infusion into sheep and ewes. In this study, the effects of EGF on basal and stimulated thyroid hormone secretion were investigated in the mouse. Mice were pretreated with /sup 125/I and thyroxine; the subsequent release of /sup 125/I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was not altered by intravenous injection of EGF (5 micrograms/animal). However, the radioiodine secretion stimulated by both TSH (120 microU/animal) and vasoactive intestinal peptide (VIP; 5 micrograms/animal) were inhibited by EGF (5 micrograms/animal). At a lower dose level (0.5 microgram/animal), EGF had no influence on stimulated radioiodine secretion. In conclusion, EGF inhibits stimulated thyroid hormone secretion in the mouse.

  10. Growth inhibition of Listeria spp. on Camembert cheese by bacteria producing inhibitory substances.

    PubMed

    Sulzer, G; Busse, M

    1991-12-01

    Bacterial strains exhibiting antimicrobial activity towards other bacteria are quite common in nature. During the past few years several genera have been shown to exert inhibitory action against Listeria. spp. In the present work strains of Enterococcus, Lactobacillus and Lactococcus were tested for their influence on the development of Listeria spp. on Camembert cheese. Partial or complete inhibition of growth of Listeria spp. was observed using various inhibitory bacteria. Complete inhibition occurred when the inhibitory strain was used as a starter culture and there was a low level of contamination with Listeria spp. during the first stage of ripening. Very little inhibition occurred if the inhibitory strain was added together with the starter culture. PMID:1790105

  11. HIV protease inhibitor nelfinavir inhibits growth of human melanoma cells by induction of cell cycle arrest.

    PubMed

    Jiang, Wei; Mikochik, Peter J; Ra, Jin H; Lei, Hanqin; Flaherty, Keith T; Winkler, Jeffrey D; Spitz, Francis R

    2007-02-01

    HIV protease inhibitors (HIV PI) are a class of antiretroviral drugs that are designed to target the viral protease. Unexpectedly, this class of drugs is also reported to have antitumor activity. In this study, we have evaluated the in vitro activity of nelfinavir, a HIV PI, against human melanoma cells. Nelfinavir inhibits the growth of melanoma cell lines at low micromolar concentrations that are clinically attainable. Nelfinavir promotes apoptosis and arrests cell cycle at G(1) phase. Cell cycle arrest is attributed to inhibition of cyclin-dependent kinase 2 (CDK2) and concomitant dephosphorylation of retinoblastoma tumor suppressor. We further show that nelfinavir inhibits CDK2 through proteasome-dependent degradation of Cdc25A phosphatase. Our results suggest that nelfinavir is a promising candidate chemotherapeutic agent for advanced melanoma, for which novel and effective therapies are urgently needed. PMID:17283158

  12. BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and suppresses the growth of solid tumors.

    PubMed

    Tsuchida, R; Osawa, T; Wang, F; Nishii, R; Das, B; Tsuchida, S; Muramatsu, M; Takahashi, T; Inoue, T; Wada, Y; Minami, T; Yuasa, Y; Shibuya, M

    2014-07-17

    Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent studies have suggested that BMP4 inhibits the survival of cancer stem cells (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and consequently suppressed tumor growth in vivo. Although HeLa (human cervical cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of xeno- and allografts of these cells was suppressed via reductions in tumor angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA expression of major angiogenesis-related factors in grafted tumors, we found that the expression of TSP1 was significantly upregulated by BMP4 administration. We then confirmed that BMP4 was less effective in suppressing the tumor growth of TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner, which indicates that BMP4 interfered with the stabilization of tumor angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor angiogenesis in the tumor microenvironment, which subsequently reduced the growth of tumors. BMP4 may become an antitumor agent and open a new field of antiangiogenic therapy. PMID:24013228

  13. Large plasma-membrane depolarization precedes rapid blue-light-induced growth inhibition in cucumber

    NASA Technical Reports Server (NTRS)

    Spalding, E. P.; Cosgrove, D. J.

    1989-01-01

    Blue-light (BL)-induced suppression of elongation of etiolated Cucumis sativus L. hypocotyls began after a 30-s lag time, which was halved by increasing the fluence rate from 10 to 100 micromoles m-2 s-1. Prior to the growth suppression, the plasma-membrane of the irradiated cells depolarized by as much as 100 mV, then returned within 2-3 min to near its initial value. The potential difference measured with surface electrodes changed with an identical time course but opposite polarity. The lag time for the change in surface potential showed an inverse dependence on fluence rate, similar to the lag for the growth inhibition. Green light and red light caused neither the electrical response nor the rapid inhibition of growth. The depolarization by BL did not propagate to nonirradiated regions and exhibited a refractory period of about 10 min following a BL pulse. Fluence-response relationships for the electrical and growth responses provide correlational evidence that the plasma-membrane depolarization reflects an event in the transduction chain of this light-growth response.

  14. miR-100 Inhibits the Growth and Migration of Burn-Denatured Fibroblasts

    PubMed Central

    Ying, Jianghui; Liu, Yunfeng; Yang, Ruijin; Zhang, Yong; Xu, Jianjun

    2016-01-01

    Background Burn-denatured dermis is able to regain the function and shape of normal dermis; however, the potential mechanisms are still vague. The aim of this study was to investigate roles of miR-100 involved in the growth and migration of burn-denatured fibroblasts. Material/Methods Quantitative real-time polymerase chain reaction(qRT-PCR) was used to assess the expression of miR-100. Transient transfection of miR-100 mimics and inhibitor was used to up-regulate or down-regulate the expression of miR-100. Cell proliferation and colony formation assay were used to test the cell growth, and wound healing assay and transwell migration assay were used to evaluate the cell migration. Results miR-100 expression was notably downregulated in the burn-denatured fibroblasts compared to normal controls. Functionally, transfection of miR-100 inhibitors improved the growth and migration abilities of burn-denatured fibroblasts. In contrast, upregulation of miR-100 inhibits the growth and migration of burn-denatured fibroblasts. Conclusions Based on these observations, we concluded that miR-100 can inhibit the growth and migration of burn-denatured fibroblasts. PMID:26928010

  15. Inhibition of Human Colon Cancer Growth by Antibody-Directed Human LAK Cells in SCID Mice

    NASA Astrophysics Data System (ADS)

    Takahashi, Hiroshi; Nakada, Tetsuya; Puisieux, Isabelle

    1993-03-01

    Advanced human colon cancer does not respond to lymphokine-activated killer (LAK) cells. In order to direct cytotoxic cells to the tumor, human LAK cells linked with antibodies to a tumor cell surface antigen were tested with established hepatic metastases in severe combined immunodeficient (SCID) mice. These cells had increased uptake into the tumor and suppression of tumor growth as compared with LAK cells alone, thereby improving the survival of tumor-bearing mice. Thus, tumor growth can be inhibited by targeted LAK cells, and SCID mice can be used to test the antitumor properties of human effector cells.

  16. Generalization of Monod kinetics for analysis of growth data with substrate inhibition

    SciTech Connect

    Luong, J.H.T.

    1987-02-05

    The inhibitory effect of butanol on yeast growth has been studied for the strain Candida utilis ATCC 8205 growing aerobically on butanol under batch conditions. A mathematical expression was then proposed to fit the kinetic pattern of butanol inhibition on the specific growth rate. The maximum allowable butanol concentration above which cells do not grow was predicted to be 9.16 g/l. The proposed model appears to accurately represent the experimental data obtained in this study and the literature data developed for a variety of batch culture systems at widely ranging substrate concentrations. 20 references.

  17. Ambroxol inhibits platelet-derived growth factor production in human monocytic cells.

    PubMed

    Utsugi, Mitsuyoshi; Dobashi, Kunio; Koga, Yasuhiko; Masubuchi, Ken; Shimizu, Yasuo; Endou, Katsuaki; Nakazawa, Tsugio; Mori, Masatomo

    2002-02-01

    Several growth factors, including platelet-derived growth factor (PDGF), have been implicated in the mechanism of lung and airway remodeling. We investigated the effect of ambroxol, trans-4-[(2-amino-3,5-dibromobenzyl) amino] cyclohexanol hydrochloride, on the lipopolysaccharide-induced PDGF production in human monocytic cells, THP-1. Ambroxol inhibited the lipopolysaccharide-induced PDGF-AB production via PDGF-A mRNA expression. Lipopolysaccharide activated p44/42 extracellular signal-regulated kinase (ERK), and ambroxol attenuated the lipopolysaccharide-induced p44/42 ERK activation. Furthermore, mitogen-activated protein kinase kinase (MEK)-1-specific inhibitor, 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD 98059), blocked the lipopolysaccharide-induced p44/42 ERK activation and PDGF production. These findings indicate that ambroxol inhibits the lipopolysaccharide-induced PDGF production due to the suppression of p44/42 ERK activity. PMID:11834245

  18. Glaucocalyxin A inhibits the growth of liver cancer Focus and SMMC-7721 cells

    PubMed Central

    TANG, LISHA; JIN, XIAOFENG; HU, XIAOHUI; HU, XIAODING; LIU, ZULONG; YU, LONG

    2016-01-01

    Liver cancer is one of the most common types of cancer, and hepatoma demonstrates a poor long-term prognosis. The present study reports that glaucocalyxin A (GLA), a natural product isolated from Rabdosia umbrosa, inhibits the growth of the liver cancer Focus and SMMC-7721 cell lines in a dose- and time-dependent manner. The present study revealed that GLA arrested the liver cancer cells at the G2/M stage of the cell cycle and led to decreased expression of caspase 3 and the cleavage of poly(adenosine diphosphate-ribose) polymerase. Overall, the present study demonstrated that GLA inhibits the growth of liver cancer cells by G2/M stage cell-cycle arrest and cell apoptosis. PMID:26893714

  19. Zinc pyrithione inhibits yeast growth through copper influx and inactivation of iron-sulfur proteins.

    PubMed

    Reeder, Nancy L; Kaplan, Jerry; Xu, Jun; Youngquist, R Scott; Wallace, Jared; Hu, Ping; Juhlin, Kenton D; Schwartz, James R; Grant, Raymond A; Fieno, Angela; Nemeth, Suzanne; Reichling, Tim; Tiesman, Jay P; Mills, Tim; Steinke, Mark; Wang, Shuo L; Saunders, Charles W

    2011-12-01

    Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal. PMID:21947398

  20. Farnesyltransferase inhibitor R115777 inhibits cell growth and induces apoptosis in mantle cell lymphoma

    PubMed Central

    Rolland, Delphine; Camara-Clayette, Valérie; Barbarat, Aurélie; Salles, Gilles; Coiffier, Bertrand; Ribrag, Vincent; Thieblemont, Catherine

    2008-01-01

    The cytotoxic activity of the farnesyltranseferase inhibitor R115777 was evaluated in cell lines representative of mantle cell lymphoma (MCL). Cell growth, proliferation, and apoptosis were analyzed in four human MCL cell lines (Granta, NCEB, REC, and UPN1) in presence of R115777, alone or in combination with vincristin, doxorubicin, bortezomib, cisplatin and cytarabine. Inhibition of farnesylation was determined by the appearance of prelamin A. The antitumor activity of R115777, administered p.o. at 100, 250 and 500mg/kg, was determined in vivo in nude mice xenografted with UPN1 cells. R115777 inhibited the growth of MCL cell lines in vitro with inhibitory concentrations ranging between 2 and 15nM. A fifty percent decrease of cell viability was observed at concentrations comprised between 0.08 and 17μM. Apoptosis, evaluated by annexin V and activated caspase 3 staining, was induced in all cell lines, in 40 to 71% of the cells depending on the cell lines. In addition, R115777 significantly increased the cytotoxic effect of vincristine, doxorubicin, bortezomib, cisplatin and cytarabine (p=0.001, p=0.016, p=0.006, p=0.014 and p=0.007 respectively). Exposure of MCL cell lines to R115777 during 72 hours resulted in inhibition of protein farnesylation. R115777 administered p.o. twice daily for 8 consecutive days to mice bearing established s.c. UPN1 xenograft displayed cytostatic activity at the 500 mg/kg dosage. We have demonstrated that inhibition of farnesyltransferase by R115777 was associated with growth inhibition and apoptosis of MCL cell lines in vitro and tumor xenograft stability in vivo. PMID:17639395

  1. Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo

    SciTech Connect

    Chian, Song; Thapa, Ruby; Chi, Zhexu; Wang, Xiu Jun; Tang, Xiuwen

    2014-05-16

    Highlights: • Luteolin inhibits the Nrf2 pathway in mouse liver and in xenografted tumors. • Luteolin markedly inhibits the growth of xenograft tumors. • Luteolin enhances the anti-cancer effect of cisplatin in mice in vivo. • Luteolin could serve as an adjuvant in the chemotherapy of NSCLC. - Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is over-expressed in many types of tumor, promotes tumor growth, and confers resistance to anticancer therapy. Hence, Nrf2 is regarded as a novel therapeutic target in cancer. Previously, we reported that luteolin is a strong inhibitor of Nrf2 in vitro. Here, we showed that luteolin reduced the constitutive expression of NAD(P)H quinone oxidoreductase 1 in mouse liver in a time- and dose-dependent manner. Further, luteolin inhibited the expression of antioxidant enzymes and glutathione transferases, decreasing the reduced glutathione in the liver of wild-type mice under both constitutive and butylated hydroxyanisole-induced conditions. In contrast, such distinct responses were not detected in Nrf2{sup −/−} mice. In addition, oral administration of luteolin, either alone or combined with intraperitoneal injection of the cytotoxic drug cisplatin, greatly inhibited the growth of xenograft tumors from non-small-cell lung cancer (NSCLC) cell line A549 cells grown subcutaneously in athymic nude mice. Cell proliferation, the expression of Nrf2, and antioxidant enzymes were all reduced in tumor xenograft tissues. Furthermore, luteolin enhanced the anti-cancer effect of cisplatin. Together, our findings demonstrated that luteolin inhibits the Nrf2 pathway in vivo and can serve as an adjuvant in the chemotherapy of NSCLC.

  2. Nitric oxide reversibly inhibits the epidermal growth factor receptor tyrosine kinase.

    PubMed Central

    Estrada, C; Gómez, C; Martín-Nieto, J; De Frutos, T; Jiménez, A; Villalobo, A

    1997-01-01

    Although it has been demonstrated that NO inhibits the proliferation of different cell types, the mechanisms of its anti-mitotic action are not well understood. In this work we have studied the possible interaction of NO with the epidermal growth factor receptor (EGFR), using transfected fibroblasts which overexpress the human EGFR. The NO donors S-nitroso-N-acetylpenicillamine (SNAP), 1,1-diethyl-2-hydroxy-2-nitrosohydrazine (DEA-NO) and N-¿4-[1-(3-aminopropyl)-2-hydroxy-2-nitrosohydrazino]butyl¿propane -1, 3-diamine (DETA-NO) inhibited DNA synthesis of fibroblasts growing in the presence of fetal calf serum, epidermal growth factor (EGF) or EGF plus insulin, as assessed by [methyl-3H]thymidine incorporation. Neither 8-bromo-cGMP nor the cGMP-phosphodiesterase inhibitor zaprinast mimicked this effect, suggesting that NO is unlikely to inhibit cell proliferation via a cGMP-dependent pathway. SNAP, DEA-NO and DETA-NO also inhibited the transphosphorylation of the EGFR and its tyrosine kinase activity toward the exogenous substrate poly-l-(Glu-Tyr), as measured in permeabilized cells using [gamma-32P]ATP as phosphate donor. In contrast, 3-[morpholinosydnonimine hydrochloride] (SIN-1), a peroxynitrite-forming compound, did not significantly inhibit either DNA synthesis or the EGFR tyrosine kinase activity. The inhibitory action of DEA-NO on the EGFR tyrosine kinase was prevented by haemoglobin, an NO scavenger, but not by superoxide dismutase, and was reversed by dithiothreitol. The binding of EGF to its receptor was unaffected by DEA-NO. The inhibitory action of DEA-NO on the EGF-dependent transphosphorylation of the receptor was also demonstrated in intact cells by immunoblot analysis using an anti-phosphotyrosine antibody. Taken together, these results suggest that NO, but not peroxynitrite, inhibits in a reversible manner the EGFR tyrosine kinase activity by S-nitrosylation of the receptor. PMID:9291107

  3. RARalpha is a regulatory factor for Am-80-induced cell growth inhibition of hematologic malignant cells.

    PubMed

    Jimi, Shiro; Mashima, Kota; Matsumoto, Taichi; Hara, Shuji; Suzumiya, Junji; Tamura, Kazuo

    2007-08-01

    Retinoids are used for treatment of acute promyelocytic leukemia (APL). Am-80, Tamibarotene, binds to retinoic acid receptor alpha (RARalpha) more specifically than all-trans retinoic acid. We studied the tumor cell suppressive effects of Am-80, with respect to cytotoxicity and growth inhibition using eight myeloid and lymphoid malignant cells in culture (HL-60, HL-60R, K-562, Kasumi-1, MEG01, Raji, U266B1, and U937). The effects of Am-80 were examined during 9 days of incubation with 10(-7)-10(-5) M of Am-80 in culture medium, which was changed every 3 days. HL-60 were the only cells sensitive to Am-80-induced cytotoxicity; the latter reached more than 95% after 9 days of incubation, and death was primarily through apoptosis. The total mass of RARalpha in HL-60 was significantly greater (p<0.006) than in ATRA-resistant HL-60 (HL-60R) as well as all of other cells tested. However, in all cells excluding HL-60, Am-80 induced time- and dose-dependent cell growth inhibition without noticeable cytotoxicity. TGF-beta2 was released into the media containing cells incubated with Am-80 for 3 days. A dose-dependent increment of phosphorylation of Smad-2 was also detected. The relative amount of secreted TGF-beta2 correlated with the growth inhibition rates in all cells tested excluding HL-60, and with the total mass of RARalpha in the cells (p=0.0137). Our results indicate that Am-80-induced cell-type non-specific growth inhibition is mediated by TGF-beta2, where the total mass of RARalpha could be an important regulatory factor in hematologic malignant cells. PMID:17611697

  4. A Rho GDP Dissociation Inhibitor Produced by Apoptotic T-Cells Inhibits Growth of Mycobacterium tuberculosis

    PubMed Central

    Venkatasubramanian, Sambasivan; Dhiman, Rohan; Paidipally, Padmaja; Cheekatla, Satyanarayana S.; Tripathi, Deepak; Welch, Elwyn; Tvinnereim, Amy R.; Jones, Brenda; Theodorescu, Dan; Barnes, Peter F.; Vankayalapati, Ramakrishna

    2015-01-01

    In this study, we found that a subpopulation of CD4+CD25+ (85% Foxp3+) cells from persons with latent tuberculosis infection (LTBI) inhibits growth of M. tuberculosis (M. tb) in human monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic CD4+CD25+ (85% Foxp3+) cells is responsible for this inhibition of M. tb growth in human macrophages and in mice. M. tb-expanded CD4+CD25+Foxp3+D4GDI+ cells do not produce IL-10, TGF-β and IFN-γ. D4GDI inhibited growth of M. tb in MDMs by enhancing production of IL-1β, TNF-α and ROS, and by increasing apoptosis of M. tb-infected MDMs. D4GDI was concentrated at the site of disease in tuberculosis patients, with higher levels detected in pleural fluid than in serum. However, in response to M. tb, PBMC from tuberculosis patients produced less D4GDI than PBMC from persons with LTBI. M. tb-expanded CD4+CD25+ (85% Foxp3+) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen. Our study provides the first evidence that a subpopulation of CD4+CD25+ (85% Foxp3+) cells enhances immunity to M. tb, and that production of D4GDI by this subpopulation inhibits M. tb growth. PMID:25659138

  5. Inhibition of mammary tumor growth and metastases to bone and liver by dietary grape polyphenols.

    PubMed

    Castillo-Pichardo, Linette; Martínez-Montemayor, Michelle M; Martínez, Joel E; Wall, Kristin M; Cubano, Luis A; Dharmawardhane, Suranganie

    2009-01-01

    The cancer preventive properties of grape products such as red wine have been attributed to polyphenols enriched in red wine. However, much of the studies on cancer preventive mechanisms of grape polyphenols have been conducted with individual compounds at concentrations too high to be achieved via dietary consumption. We recently reported that combined grape polyphenols at physiologically relevant concentrations are more effective than individual compounds at inhibition of ERalpha(-), ERbeta(+) MDA-MB-231 breast cancer cell proliferation, cell cycle progression, and primary mammary tumor growth (Schlachterman et al., Transl Oncol 1:19-27, 2008). Herein, we show that combined grape polyphenols induce apoptosis and are more effective than individual resveratrol, quercetin, or catechin at inhibition of cell proliferation, cell cycle progression, and cell migration in the highly metastatic ER (-) MDA-MB-435 cell line. The combined effect of dietary grape polyphenols (5 mg/kg each resveratrol, quercetin, and catechin) was tested on progression of mammary tumors in nude mice created from green fluorescent protein-tagged MDA-MB-435 bone metastatic variant. Fluorescence image analysis of primary tumor growth demonstrated a statistically significant decrease in tumor area by dietary grape polyphenols. Molecular analysis of excised tumors demonstrated that reduced mammary tumor growth may be due to upregulation of FOXO1 (forkhead box O1) and NFKBIA (IkappaBalpha), thus activating apoptosis and potentially inhibiting NfkappaB (nuclear factor kappaB) activity. Image analysis of distant organs for metastases demonstrated that grape polyphenols reduced metastasis especially to liver and bone. Overall, these results indicate that combined dietary grape polyphenols are effective at inhibition of mammary tumor growth and site-specific metastasis. PMID:19294520

  6. Cabozantinib inhibits prostate cancer growth and prevents tumor-induced bone lesions

    PubMed Central

    Dai, Jinlu; Zhang, Honglai; Karatsinides, Andreas; Keller, Jill M.; Kozloff, Kenneth M.; Aftab, Dana T.; Schimmoller, Frauke; Keller, Evan T.

    2013-01-01

    Purpose Cabozantinib, an orally available multi-tyrosine kinase inhibitor with activity against MET and vascular endothelial growth factor receptor 2 (VEGFR2), induces resolution of bone scan lesions in men with castration-resistant prostate cancer bone metastases. The purpose of this study was to determine whether cabozantinib elicited a direct anti-tumor effect, an indirect effect through modulating bone, or both. Experimental Design Using human prostate cancer xenograft studies in mice we determined cabozantinib's impact on tumor growth in soft tissue and bone. In vitro studies with cabozantinib were performed using (1) prostate cancer cell lines to evaluate its impact on cell growth, invasive ability and MET and (2) osteoblast cell lines to evaluate its impact on viability and differentiation and VEGFR2. Results Cabozantinib inhibited progression of multiple prostate cancer cell lines (Ace-1,C4-2B, and LuCaP 35) in bone metastatic and soft tissue murine models of prostate cancer, except for PC-3 prostate cancer cells in which it inhibited only subcutaneous growth. Cabozantinib directly inhibited prostate cancer cell viability and induced apoptosis in vitro and in vivo and inhibited cell invasion in vitro. Cabozantinib had a dose-dependent biphasic effect on osteoblast activity and inhibitory effect on osteoclast production in vitro, that was reflected in vivo. It blocked MET and VEGFR2 phosphorylation in prostate cancer cells and osteoblast-like cells, respectively. Conclusion These data indicate that cabozantinib has direct anti-tumor activity; and that its ability to modulate osteoblast activity may contribute to its anti-tumor efficacy. PMID:24097861

  7. Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta.

    PubMed Central

    Kooistra, A.; van den Eijnden-van Raaij, A. J.; Klaij, I. A.; Romijn, J. C.; Schröder, F. H.

    1995-01-01

    The paracrine influence of prostatic stroma on the proliferation of prostatic epithelial cells was investigated. Stromal cells from the human prostate have previously been shown to inhibit anchorage-dependent as well as anchorage-independent growth of the prostatic tumour epithelial cell lines PC-3 and LNCaP. Antiproliferative activity, mediated by a diffusible factor in the stromal cell conditioned medium, was found to be produced specifically by prostatic stromal cells. In the present study the characteristics of this factor were examined. It is demonstrated that prostate stroma-derived inhibiting factor is an acid- and heat-labile, dithiothreitol-sensitive protein. Although some similarities with type beta transforming growth factor (TGF-beta)-like inhibitors are apparent, evidence is presented that the factor is not identical to TGF-beta or to the TGF-beta-like factors activin and inhibin. Absence of TGF-beta activity was shown by the lack of inhibitory response of the TGF-beta-sensitive mink lung cell line CCL-64 to prostate stromal cell conditioned medium and to concentrated, partially purified preparations of the inhibitor. Furthermore, neutralising antibodies against TGF-beta 1 or TGF-beta 2 did not cause a decline in the level of PC-3 growth inhibition caused by partially purified inhibitor. Using Northern blot analyses, we excluded the involvement of inhibin or activin. It is concluded that the prostate stroma-derived factor may be a novel growth inhibitor different from any of the currently described inhibiting factors. Images Figure 5 PMID:7543773

  8. Salicylic acid antagonizes abscisic acid inhibition of shoot growth and cell cycle progression in rice

    NASA Astrophysics Data System (ADS)

    Meguro, Ayano; Sato, Yutaka

    2014-04-01

    We analysed effects of abscisic acid (ABA, a negative regulatory hormone), alone and in combination with positive or neutral hormones, including salicylic acid (SA), on rice growth and expression of cell cycle-related genes. ABA significantly inhibited shoot growth and induced expression of OsKRP4, OsKRP5, and OsKRP6. A yeast two-hybrid assay showed that OsKRP4, OsKRP5, and OsKRP6 interacted with OsCDKA;1 and/or OsCDKA;2. When SA was simultaneously supplied with ABA, the antagonistic effect of SA completely blocked ABA inhibition. SA also blocked ABA inhibition of DNA replication and thymidine incorporation in the shoot apical meristem. These results suggest that ABA arrests cell cycle progression by inducing expression of OsKRP4, OsKRP5, and OsKRP6, which inhibit the G1/S transition, and that SA antagonizes ABA by blocking expression of OsKRP genes.

  9. Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines

    SciTech Connect

    Takasawa, Wataru; Ohnuma, Kei; Hatano, Ryo; Endo, Yuko; Dang, Nam H.

    2010-10-08

    Research highlights: {yields} TNF-{alpha} or IL-1{beta} induces EC proliferation with reduction of CD26 expression. {yields} CD26 siRNA or DPP-4 inhibition enhances TNF-{alpha} or IL-1{beta}-induced EC proliferation. {yields} Loss of CD26/DPP-4 enhances aortic sprouting induced by TNF-{alpha} or IL-1{beta}. {yields} Capillary formation induced by TNF-{alpha} or IL-1{beta} is enahced in the CD26{sup -/-} mice. -- Abstract: CD26/DPP-4 is abundantly expressed on capillary of inflamed lesion as well as effector T cells. Recently, CD26/dipeptidyl peptidase 4 (DPP-4) inhibition has been used as a novel oral therapeutic approach for patients with type 2 diabetes. While accumulating data indicate that vascular inflammation is a key feature of both micro- and macro-vascular complications in diabetes, the direct role of CD26/DPP-4 in endothelial biology is to be elucidated. We herein showed that proinflammatory cytokines such as tumor necrosis factor or interleukin-1 reduce expression of CD26 on microvascular endothelial cells, and that genetical or pharmacological inhibition of CD26/DPP-4 enhances endothelial growth both in vitro and in vivo. With DPP-4 inhibitors being used widely in the treatment of type 2 diabetes, our data strongly suggest that DPP-4 inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications.

  10. Methylthioadenosine (MTA) inhibits melanoma cell proliferation and in vivo tumor growth

    PubMed Central

    2010-01-01

    Background Melanoma is the most deadly form of skin cancer without effective treatment. Methylthioadenosine (MTA) is a naturally occurring nucleoside with differential effects on normal and transformed cells. MTA has been widely demonstrated to promote anti-proliferative and pro-apoptotic responses in different cell types. In this study we have assessed the therapeutic potential of MTA in melanoma treatment. Methods To investigate the therapeutic potential of MTA we performed in vitro proliferation and viability assays using six different mouse and human melanoma cell lines wild type for RAS and BRAF or harboring different mutations in RAS pathway. We also have tested its therapeutic capabilities in vivo in a xenograft mouse melanoma model and using variety of molecular techniques and tissue culture we investigated its anti-proliferative and pro-apoptotic properties. Results In vitro experiments showed that MTA treatment inhibited melanoma cell proliferation and viability in a dose dependent manner, where BRAF mutant melanoma cell lines appear to be more sensitive. Importantly, MTA was effective inhibiting in vivo tumor growth. The molecular analysis of tumor samples and in vitro experiments indicated that MTA induces cytostatic rather than pro-apoptotic effects inhibiting the phosphorylation of Akt and S6 ribosomal protein and inducing the down-regulation of cyclin D1. Conclusions MTA inhibits melanoma cell proliferation and in vivo tumor growth particularly in BRAF mutant melanoma cells. These data reveal a naturally occurring drug potentially useful for melanoma treatment. PMID:20529342

  11. SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin.

    PubMed

    Dai, Lei; Cui, Xueliang; Zhang, Xin; Cheng, Lin; Liu, Yi; Yang, Yang; Fan, Ping; Wang, Qingnan; Lin, Yi; Zhang, Junfeng; Li, Chunlei; Mao, Ying; Wang, Qin; Su, Xiaolan; Zhang, Shuang; Peng, Yong; Yang, Hanshuo; Hu, Xun; Yang, Jinliang; Huang, Meijuan; Xiang, Rong; Yu, Dechao; Zhou, Zongguang; Wei, Yuquan; Deng, Hongxin

    2016-01-01

    SARI, also called as BATF2, belongs to the BATF family and has been implicated in cancer cell growth inhibition. However, the role and mechanism of SARI in tumour angiogenesis are elusive. Here we demonstrate that SARI deficiency facilitates AOM/DSS-induced colonic tumorigenesis in mice. We show that SARI is a novel inhibitor of colon tumour growth and angiogenesis in mice. Antibody array and HUVEC-related assays indicate that VEGF has an essential role in SARI-controlled inhibition of angiogenesis. Furthermore, Co-IP/PAGE/mass spectrometry indicates that SARI directly targets ceruloplasmin (Cp), and induces protease degradation of Cp, thereby inhibiting the activity of the HIF-1α/VEGF axis. Tissue microarray results indicate that SARI expression inversely correlates with poor clinical outcomes in colon cancer patients. Collectively, our results indicate that SARI is a potential target for therapy by inhibiting angiogenesis through the reduction of VEGF expression and is a prognostic indicator for patients with colon cancer. PMID:27353863

  12. SARI inhibits angiogenesis and tumour growth of human colon cancer through directly targeting ceruloplasmin

    PubMed Central

    Dai, Lei; Cui, Xueliang; Zhang, Xin; Cheng, Lin; Liu, Yi; Yang, Yang; Fan, Ping; Wang, Qingnan; Lin, Yi; Zhang, Junfeng; Li, Chunlei; Mao, Ying; Wang, Qin; Su, Xiaolan; Zhang, Shuang; Peng, Yong; Yang, Hanshuo; Hu, Xun; Yang, Jinliang; Huang, Meijuan; Xiang, Rong; Yu, Dechao; Zhou, Zongguang; Wei, Yuquan; Deng, Hongxin

    2016-01-01

    SARI, also called as BATF2, belongs to the BATF family and has been implicated in cancer cell growth inhibition. However, the role and mechanism of SARI in tumour angiogenesis are elusive. Here we demonstrate that SARI deficiency facilitates AOM/DSS-induced colonic tumorigenesis in mice. We show that SARI is a novel inhibitor of colon tumour growth and angiogenesis in mice. Antibody array and HUVEC-related assays indicate that VEGF has an essential role in SARI-controlled inhibition of angiogenesis. Furthermore, Co-IP/PAGE/mass spectrometry indicates that SARI directly targets ceruloplasmin (Cp), and induces protease degradation of Cp, thereby inhibiting the activity of the HIF-1α/VEGF axis. Tissue microarray results indicate that SARI expression inversely correlates with poor clinical outcomes in colon cancer patients. Collectively, our results indicate that SARI is a potential target for therapy by inhibiting angiogenesis through the reduction of VEGF expression and is a prognostic indicator for patients with colon cancer. PMID:27353863

  13. Growth inhibition and changes in morphology and actin distribution in Acetabularia acetabulum by phalloidin and phalloidin derivatives.

    PubMed

    Sawitzky, H; Hanfstingl, U; Faulstich, H

    2003-03-01

    Effects on morphology and microfilament structure caused by phalloidin, phallacidin, and some semisynthetic phalloidin derivatives were studied in vegetative cells of the green alga Acetabularia acetabulum (L.) Silva. All phalloidin derivatives (except for phalloidin itself) caused growth stop of the alga after 1 day and (except for the fluorescein-labeled phalloidin) death of the cells after 4-7 days. Hair whorl tip growth and morphology as screened by light microscopy, as well as microfilament structure in tips, suggested that growth stop is correlated with a disorganization of actin filaments similar to that recently described for jasplakinolide (H. Sawitzky, S. Liebe, J. Willingale-Theune, D. Menzel, European Journal of Cell Biology 78: 424-433, 1999). Using rabbit muscle actin as a model target protein, we found that the toxic effects in vivo did not correlate with actin affinity values, suggesting that permeation through membranes must play a role. Indeed, the most lipophilic phalloidin derivatives benzoylphalloidin and dithiolanophalloidin were the most active in causing growth stop at ca. 100 microM. In comparison to the concentration of jasplakinolide required to cause similar effects (<3 microM), the two most active phalloidin derivatives exhibited an activity ca. 30 times lower. Nonetheless, lipophilic phalloidin derivatives can be used in algae, and probably also other cells, to modulate actin dynamics in vivo. In addition, we found that the fluorescent fluorescein isothiocyanate-phalloidin is able to enter living algal cells and stains actin structures brightly. Since it does not suppress actin dynamics, we suggest fluorescein isothiocyanate-phalloidin as a tool for studying rearrangements of actin structures in live cells, e.g., by confocal laser scanning microscopy. PMID:12664285

  14. Reducing the serine availability complements the inhibition of the glutamine metabolism to block leukemia cell growth

    PubMed Central

    Polet, Florence; Corbet, Cyril; Pinto, Adan; Rubio, Laila Illan; Martherus, Ruben; Bol, Vanesa; Drozak, Xavier; Grégoire, Vincent; Riant, Olivier; Feron, Olivier

    2016-01-01

    Leukemia cells are described as a prototype of glucose-consuming cells with a high turnover rate. The role of glutamine in fueling the tricarboxylic acid cycle of leukemia cells was however recently identified confirming its status of major anaplerotic precursor in solid tumors. Here we examined whether glutamine metabolism could represent a therapeutic target in leukemia cells and whether resistance to this strategy could arise. We found that glutamine deprivation inhibited leukemia cell growth but also led to a glucose-independent adaptation maintaining cell survival. A proteomic study revealed that glutamine withdrawal induced the upregulation of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT), two enzymes of the serine pathway. We further documented that both exogenous and endogenous serine were critical for leukemia cell growth and contributed to cell regrowth following glutamine deprivation. Increase in oxidative stress upon inhibition of glutamine metabolism was identified as the trigger of the upregulation of PHGDH. Finally, we showed that PHGDH silencing in vitro and the use of serine-free diet in vivo inhibited leukemia cell growth, an effect further increased when glutamine metabolism was blocked. In conclusion, this study identified serine as a key pro-survival actor that needs to be handled to sensitize leukemia cells to glutamine-targeting modalities. PMID:26625201

  15. Cation Reversal of Inhibition of Growth by Valinomycin in Streptococcus pyogenes and Clostridium sporogenes1

    PubMed Central

    Seshachalam, Dutta; Frahm, David H.; Ferraro, Frank M.

    1973-01-01

    Study of the antimicrobial spectrum of valinomycin revealed that, in addition to the gram-positive bacteria reported in literature, Streptococcus pyogenes and Clostridium sporogenes are also susceptible to this antibiotic. The minimal inhibitory concentrations (MIC) of the antibiotic for S. pyogenes grown aerobically and anaerobically did not differ markedly, negating the hypothesis that oxidative phosphorylation is involved in the mechanism of action of this antibiotic. This conclusion is further strengthened by the inhibition of growth of C. sporogenes, an obligate anaerobe. In a medium with a low K+ concentration, the MIC for S. pyogenes was 0.02 μg/ml, the lowest ever recorded for this antibiotic. The inhibition of growth of S. pyogenes and C. sporogenes was readily reversed by addition of K+ to the medium, indicating a compensation for net efflux of K+ from the cells when the transmembrane potential reached equilibrium. In contrast to these bacteria, Bacillus subtilis was less susceptible to the antibiotic when the potassium concentration of the medium was low. The addition of potassium in the presence of valinomycin increased the inhibition of growth, which appears to result from dissipation of metabolic energy as in the mitochondrial system. PMID:4208280

  16. Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein

    SciTech Connect

    Lim, Jung Yeon; Kim, Hongtae; Jeun, Sin-Soo . E-mail: ssjeun@catholic.ac.kr; Kang, Seok-Gu; Lee, Kyung-Jin

    2006-02-24

    Numerous studies have suggested that the NF2 protein merlin is involved in the regulation of abnormal cell growth and proliferation. In this study, to better understand the merlin's mechanisms that contribute to the inhibition of tumorigenesis, we examined the potential action of merlin on the cell proliferative signaling pathways in response to growth hormone (GH). Merlin effectively attenuated the GH-induced serum response element (SRE) and Elk-1-mediated transcriptional activation, as well as the endogenous SRE-regulated gene c-fos expression in NIH3T3 cells. In addition, merlin prevented the Raf-1 complex activation process, which resulted in the suppression of MAP kinase/ERK, extracellular signal-regulated kinase (ERKs), and Elk-1 phosphorylation, which are the downstream signals of Raf-1. Moreover, it was shown that merlin interacted with endogenous growth factor receptor bound 2 (Grb2) protein and inhibited its expression. These results suggest that merlin contributes, via its protein-to-protein interaction with Grb2 and consequent inhibition of the MAPK pathways, to the regulation of the abnormal cell proliferation, and this provides a further mechanism underlying the tumor suppressor function of merlin.

  17. Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression.

    PubMed

    Chen, Xiaowan; Li, Chenli; He, Tiantian; Mao, Jiating; Li, Chunmei; Lyu, Jianxin; Meng, Qing H

    2016-05-01

    Metformin has been reported to inhibit the growth of various types of cancers, including prostate cancer. Yet the mode of anti-cancer action of metformin and the underlying mechanisms remain not fully elucidated. We hypothesized that the antitumorigenic effects of metformin are mediated through upregulation of pigment epithelium-derived factor (PEDF) expression in prostate cancer cells. In this report, metformin treatment significantly inhibited the proliferation and colony formation of prostate cancer cells, in a dose- and time-dependent manner. Meanwhile, Metformin markedly suppressed migration and invasion and induced apoptosis of both LNCaP and PC3 cancer cells. Metformin also reduced PC3 tumor growth in BALB/c nude mice in vivo. Furthermore, metformin treatment was associated with higher PEDF expression in both prostate cancer cells and tumor tissue. Taken together, metformin inhibits prostate cancer cell proliferation, migration, invasion and tumor growth, and these activities are mediated by upregulation of PEDF expression. These findings provide a novel insight into the molecular functions of metformin as an anticancer agent. PMID:26987032

  18. Monocarbonyl analogs of curcumin inhibit growth of antibiotic sensitive and resistant strains of Mycobacterium tuberculosis

    PubMed Central

    Baldwin, Patrick R.; Reeves, Analise Z.; Powell, Kimberly R.; Napier, Ruth J.; Swimm, Alyson I.; Sun, Aiming; Giesler, Kyle; Bommarius, Bettina; Shinnick, Thomas M.; Snyder, James P.; Liotta, Dennis C.; Kalman, Daniel

    2016-01-01

    Tuberculosis (TB) is a major public health concern worldwide with over 2 billion people currently infected. The rise of strains of Mycobacterium tuberculosis (Mtb) that are resistant to some or all first and second line antibiotics, including multidrug-resistant (MDR), extensively drug resistant (XDR) and totally drug resistant (TDR) strains, is of particular concern and new anti-TB drugs are urgently needed. Curcumin, a natural product used in traditional medicine in India, exhibits anti-microbial activity that includes Mtb, however it is relatively unstable and suffers from poor bioavailability. To improve activity and bioavailability, mono-carbonyl analogs of curcumin were synthesized and screened for their capacity to inhibit the growth of Mtb and the related Mycobacterium marinum (Mm). Using disk diffusion and liquid culture assays, we found several analogs that inhibit in vitro growth of Mm and Mtb, including rifampicin-resistant strains. Structure activity analysis of the analogs indicated that Michael acceptor properties are critical for inhibitory activity. However, no synergistic effects were evident between the monocarbonyl analogs and rifampicin on inhibiting growth. Together, these data provide a structural basis for the development of analogs of curcumin with pronounced anti-mycobacterial activity and provide a roadmap to develop additional structural analogs that exhibit more favorable interactions with other anti-TB drugs. PMID:25618016

  19. In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides

    PubMed Central

    Fluiter, Kees; ten Asbroek, Anneloor L. M. A.; de Wissel, Marit B.; Jakobs, Marja E.; Wissenbach, Margit; Olsson, Håkan; Olsen, Otto; Oerum, Henrik; Baas, Frank

    2003-01-01

    Locked nucleic acids (LNA) are novel high-affinity DNA analogs that can be used as genotype-specific drugs. The LNA oligonucleotides (LNA PO ODNs) are very stable in vitro and in vivo without the need for a phosphorothiolated backbone. In this study we tested the biological fate and the efficacy in tumor growth inhibition of antisense oligonucleotides directed against the gene of the large subunit of RNA polymerase II (POLR2A) that are completely synthesized as LNA containing diester backbones. These full LNA oligonucleotides strongly reduce POLR2A protein levels. Full LNA PO ODNs appeared to be very stable compounds when injected into the circulation of mice. Full LNA PO ODNs were continuously administered for 14 days to tumor-bearing nude mice. Tumor growth was inhibited sequence specifically at dosages from 1 mg/kg/day. LNA PO ODNs appeared to be non-toxic at dosages <5 mg/kg/day. Biodistribution studies showed the kidneys to have the highest uptake of LNA PO ODNs and urinary secretion as the major route of clearance. This report shows that LNA PO ODNs are potent genotype-specific drugs that can inhibit tumor growth in vivo. PMID:12560491

  20. Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma

    PubMed Central

    Farnebo, Lovisa; Shahangian, Arash; Lee, Yunqin; Shin, June Ho; Scheeren, Ferenc A.; Sunwoo, John B.

    2015-01-01

    Infection-driven inflammation has been proposed to be involved in the tumorigenesis of head and neck squamous cell carcinoma (HNSCC). Oral HNSCC is often colonized with microbes such as gram-positive bacteria and yeast, where ligands derived from their wall components have been shown to specifically bind to Toll-like receptor 2 (TLR2). Although TLR2 has been described to be expressed in oral HNSCC, its function has not been well characterized. Here, we show the expression of TLR2 in both HNSCC cell lines and primary patient-derived HNSCC xenograft tumors. Activation of TLR2 with a yeast-derived ligand of TLR2, zymosan, promoted organoid formation in an ex vivo model of tumor growth, while blockade with anti-TLR2 antibodies inhibited organoid formation. Zymosan also induced phosphorylation of ERK and the p65 subunit of NF-κB, which was inhibited in the presence of anti-TLR2 antibodies, indicating that this receptor is functional in HNSCC and that the signaling through these pathways is intact. TLR2 blockade also inhibited growth of human xenografted tumors in immunodeficient mice. In summary, our data show that TLR2 is a functional receptor expressed in human HNSCC that plays a direct pro-tumorigenic role, and that it can be therapeutically targeted with blocking antibodies to reduce tumor growth. PMID:25846753

  1. Inhibition of hydroxyapatite growth by casein, a potential salivary phosphoprotein homologue.

    PubMed

    Romero, Maria J R H; Nakashima, Syozi; Nikaido, Toru; Ichinose, Shizuko; Sadr, Alireza; Tagami, Junji

    2015-08-01

    Salivary phosphoproteins are essential in tooth mineral regulation but are often overlooked in vitro. This study aimed to evaluate the effect of casein, as a salivary phosphoprotein homologue, on the deposition and growth of hydroxyapatite (HA) on tooth surfaces. Hydroxyapatite growth was quantified using seeded crystal systems. Artificial saliva (AS) containing HA powder and 0, 10, 20, 50, or 100 μg ml(-1) of casein, or 100 μg ml(-1) of dephosphorylated casein (Dcasein), was incubated for 0-8 h at 37°C, pH 7.2. Calcium concentrations were measured using atomic absorption spectroscopy (AAS). Surface precipitation of HA on bovine enamel and dentine blocks, incubated in similar conditions for 7 d, was examined using field emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM) with selected area electron diffraction (SAED). Casein adsorption was assessed using modified Lowry assays and zeta-potential measurements. The AAS results revealed a concentration-dependent inhibition of calcium consumption. Hydroxyapatite precipitation occurred when no casein was present, whereas precipitation of HA was apparently completely inhibited in casein-containing groups. Adsorption data demonstrated increasingly negative zeta-potential with increased casein concentration and an affinity constant similar to proline-rich proteins with Langmuir modelling. Casein inhibited the deposition and growth of HA primarily through the binding of esterized phosphate to HA active sites, indicating its potential as a mineral-regulating salivary phosphoprotein homologue in vitro. PMID:26083784

  2. Ultrasound-mediated interferon {beta} gene transfection inhibits growth of malignant melanoma

    SciTech Connect

    Yamaguchi, Kazuki; Feril, Loreto B.; Tachibana, Katsuro; Takahashi, Akira; Matsuo, Miki; Endo, Hitomi; Harada, Yoshimi; Nakayama, Juichiro

    2011-07-22

    Highlights: {yields} Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-{beta} genes both in vitro and in vivo. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited proliferation of melanoma cells in vitro. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon {beta} (IFN-{beta}) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-{beta} in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-{beta} genes mixed with microbubbles. Successful sonotransfection with IFN-{beta} gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-{beta} gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.

  3. Pharmacological inhibition of fibroblast growth factor (FGF) receptor signaling ameliorates FGF23-mediated hypophosphatemic rickets.

    PubMed

    Wöhrle, Simon; Henninger, Christine; Bonny, Olivier; Thuery, Anne; Beluch, Noemie; Hynes, Nancy E; Guagnano, Vito; Sellers, William R; Hofmann, Francesco; Kneissel, Michaela; Graus Porta, Diana

    2013-04-01

    Fibroblast growth factor 23 (FGF23) is a circulating factor secreted by osteocytes that is essential for phosphate homeostasis. In kidney proximal tubular cells FGF23 inhibits phosphate reabsorption and leads to decreased synthesis and enhanced catabolism of 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3 ). Excess levels of FGF23 cause renal phosphate wasting and suppression of circulating 1,25(OH)2 D3 levels and are associated with several hereditary hypophosphatemic disorders with skeletal abnormalities, including X-linked hypophosphatemic rickets (XLH) and autosomal recessive hypophosphatemic rickets (ARHR). Currently, therapeutic approaches to these diseases are limited to treatment with activated vitamin D analogues and phosphate supplementation, often merely resulting in partial correction of the skeletal aberrations. In this study, we evaluate the use of FGFR inhibitors for the treatment of FGF23-mediated hypophosphatemic disorders using NVP-BGJ398, a novel selective, pan-specific FGFR inhibitor currently in Phase I clinical trials for cancer therapy. In two different hypophosphatemic mouse models, Hyp and Dmp1-null mice, resembling the human diseases XLH and ARHR, we find that pharmacological inhibition of FGFRs efficiently abrogates aberrant FGF23 signaling and normalizes the hypophosphatemic and hypocalcemic conditions of these mice. Correspondingly, long-term FGFR inhibition in Hyp mice leads to enhanced bone growth, increased mineralization, and reorganization of the disturbed growth plate structure. We therefore propose NVP-BGJ398 treatment as a novel approach for the therapy of FGF23-mediated hypophosphatemic diseases. PMID:23129509

  4. Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells

    SciTech Connect

    Lin, Y.-J.; Hou, Y.C.; Lin, C.-H.; Hsu, Y.-A.; Sheu, Jim J.C.; Lai, C.-H.; Chen, B.-H.; Lee Chao, Pei-Dawn; Wan Lei Tsai, F.-J.

    2009-01-23

    Puerariae radix (PR) is a popular natural herb and a traditional food in Asia, which has antithrombotic and anti-allergic properties and stimulates estrogenic activity. In the present study, we investigated the effects of the PR isoflavones puerarin, daidzein, and genistein on the growth of breast cancer cells. Our data revealed that after treatment with PR isoflavones, a dose-dependent inhibition of cell growth occurred in HS578T, MDA-MB-231, and MCF-7 cell lines. Results from cell cycle distribution and apoptosis assays revealed that PR isoflavones induced cell apoptosis through a caspase-3-dependent pathway and mediated cell cycle arrest in the G2/M phase. Furthermore, we observed that the serum metabolites of PR (daidzein sulfates/glucuronides) inhibited proliferation of the breast cancer cells at a 50% cell growth inhibition (GI{sub 50}) concentration of 2.35 {mu}M. These results indicate that the daidzein constituent of PR can be metabolized to daidzein sulfates or daidzein glucuronides that exhibit anticancer activities. The protein expression levels of the active forms of caspase-9 and Bax in breast cancer cells were significantly increased by treatment with PR metabolites. These metabolites also increased the protein expression levels of p53 and p21. We therefore suggest that PR may act as a chemopreventive and/or chemotherapeutic agent against breast cancer by reducing cell viability and inducing apoptosis.

  5. Algae Biofuel in the Nigerian Energy Context

    NASA Astrophysics Data System (ADS)

    Elegbede, Isa; Guerrero, Cinthya

    2016-05-01

    The issue of energy consumption is one of the issues that have significantly become recognized as an important topic of global discourse. Fossil fuels production reportedly experiencing a gradual depletion in the oil-producing nations of the world. Most studies have relatively focused on biofuel development and adoption, however, the awareness of a prospect in the commercial cultivation of algae having potential to create economic boost in Nigeria, inspired this research. This study aims at exploring the potential of the commercialization of a different but commonly found organism, algae, in Nigeria. Here, parameters such as; water quality, light, carbon, average temperature required for the growth of algae, and additional beneficial nutrients found in algae were analysed. A comparative cum qualitative review of analysis was used as the study made use of empirical findings on the work as well as the author's deductions. The research explored the cultivation of algae with the two major seasonal differences (i.e. rainy and dry) in Nigeria as a backdrop. The results indicated that there was no significant difference in the contribution of algae and other sources of biofuels as a necessity for bioenergy in Nigeria. However, for an effective sustainability of this prospect, adequate measures need to be put in place in form of funding, provision of an economically-enabling environment for the cultivation process as well as proper healthcare service in the face of possible health hazard from technological processes. Further studies can seek to expand on the potential of cultivating algae in the Harmattan season.

  6. SL-01, an oral derivative of gemcitabine, inhibited human breast cancer growth through induction of apoptosis

    SciTech Connect

    Li, Yuan-Yuan; Qin, Yi-Zhuo; Wang, Rui-Qi; Li, Wen-Bao; Qu, Xian-Jun

    2013-08-23

    Highlights: •SL-01 is an oral derivative of gemcitabine. •SL-01 possessed activity against human breast cancer growth via apoptotic induction. •SL-01’s activity was more potently than that of gemcitabine. •SL-01 inhibited cancer growth without toxicity to mice. -- Abstract: SL-01 is an oral derivative of gemcitabine that was synthesized by introducing the moiety of 3-(dodecyloxycarbonyl) pyrazine-2-carbonyl at N4-position on cytidine ring of gemcitabine. We aimed to evaluate the efficacy of SL-01 on human breast cancer growth. SL-01 significantly inhibited MCF-7 proliferation as estimated by colorimetric assay. Flow cytometry assay indicated the apoptotic induction and cell cycle arrest in G1 phase. SL-01 modulated the expressions of p-ATM, p53 and p21 and decrease of cyclin D1 in MCF-7 cells. Further experiments were performed in a MCF-7 xenografts mouse model. SL-01 by oral administration strongly inhibited MCF-7 xenografts growth. This effect of SL-01 might arise from its roles in the induction of apoptosis. Immunohistochemistry assay showed the increase of TUNEL staining cells. Western blotting indicated the modulation of apoptotic proteins in SL-01-treated xenografts. During the course of study, there was no evidence of toxicity to mice. In contrast, the decrease of neutrophil cells in peripheral and increase of AST and ALT levels in serum were observed in the gemcitabine-treated mice. Conclusion: SL-01 possessed similar activity against human breast cancer growth with gemcitabine, whereas, with lower toxicity to gemcitabine. SL-01 is a potent oral agent that may supplant the use of gemcitabine.

  7. Chlorpyrifos and Chlorpyrifos-Oxon Inhibit Axonal Growth by Interfering with the Morphogenic Activity of Acetylcholinesterase

    PubMed Central

    Yang, Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

    2008-01-01

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE−/−) versus wildtype (AChE+/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE−/− DRG neurons. However, transfection of AChE−/− DRG neurons with cDNA encoding full-length AChE restored the wildtype response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs. PMID:18076960

  8. Eugenol-inhibited root growth in Avena fatua involves ROS-mediated oxidative damage.

    PubMed

    Ahuja, Nitina; Singh, Harminder Pal; Batish, Daizy Rani; Kohli, Ravinder Kumar

    2015-02-01

    Plant essential oils and their constituent monoterpenes are widely known plant growth retardants but their mechanism of action is not well understood. We explored the mechanism of phytotoxicity of eugenol, a monoterpenoid alcohol, proposed as a natural herbicide. Eugenol (100-1000 µM) retarded the germination of Avena fatua and strongly inhibited its root growth compared to the coleoptile growth. We further investigated the underlying physiological and biochemical alterations leading to the root growth inhibition. Eugenol induced the generation of reactive oxygen species (ROS) leading to oxidative stress and membrane damage in the root tissue. ROS generation measured in terms of hydrogen peroxide, superoxide anion and hydroxyl radical content increased significantly in the range of 24 to 144, 21 to 91, 46 to 173% over the control at 100 to 1000 µM eugenol, respectively. The disruption in membrane integrity was indicated by 25 to 125% increase in malondialdehyde (lipid peroxidation byproduct), and decreased conjugated diene content (~10 to 41%). The electrolyte leakage suggesting membrane damage increased both under light as well as dark conditions measured over a period from 0 to 30 h. In defense to the oxidative damage due to eugenol, a significant upregulation in the ROS-scavenging antioxidant enzyme machinery was observed. The activities of superoxide dismutases, catalases, ascorbate peroxidases, guaiacol peroxidases and glutathione reductases were elevated by ~1.5 to 2.8, 2 to 4.3, 1.9 to 5.0, 1.4 to 3.9, 2.5 to 5.5 times, respectively, in response to 100 to 1000 µM eugenol. The study concludes that eugenol inhibits early root growth through ROS-mediated oxidative damage, despite an activation of the antioxidant enzyme machinery. PMID:25752432

  9. Tracing and inhibiting growth of Staphylococcus aureus in barbecue cheese production after product recall.