In order to investigate the involvement of cyclooxygenase (COX)-2 in oral carcinogenesis and chemoprevention for it, we examined the COX-2 expression during dimethylbenzanthracene (DMBA)-induced hamster cheek pouch carcinogenesis and the inhibitory effect of sulindac, a non-steroidal anti-inflammatory drug (NSAID), on the carcinogenesis and its derived ...
PubMed
A promising approach for cancer chemoprevention might be a combination therapy utilizing dietary phytochemicals and anticarcinogenic pharmaceuticals at a suboptimal dosage to minimize any potential adverse side effects. To test this hypothesis, various dosages of anthocyanin-rich tart cherry extract were fed in combination with suboptimal levels of the nonsteroidal ...
Sulindac, a widely used non-steroidal anti-inflammatory drug (NSAID), has been shown to inhibit chemically induced carcinogenesis in animal models. In the present study, we have investigated the molecular mechanism by which sulindac affects the activity and expression of the enzymes that mediate the initial detoxification steps of many environmental ...
Although non-steroidal anti-inflammatory drugs (NSAIDs), including sulindac, have been used extensively as chemopreventive agents for colorectal cancer (CRC), results are not consistent. NSAIDs, most reportedly sulindac, often do not cause a complete regression of adenomas and some patients develop resistance to NSAID treatment. In ...
PubMed Central
Background & AimsFamilial adenomatous polyposis because of germline mutation of the adenomatous polyposis coli gene is characterized by development of colorectal adenomas and, ultimately, colorectal cancer. The usefulness of colorectal mucosal compounds to predict the effect on adenoma development of primary chemoprevention with the nonsteroidal anti-inflammatory drug ...
Non-steroidal anti-inflammatory drugs such as sulindac are promising chemoprevention agents against colon cancer, but their weak potency and side effects limit their use for both chemoprevention and chemotherapy. Here, we evaluated the effect of a new sulindac derivative, phospho-sulindac or ...
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as sulindac effectively prevent colon cancer in humans and rodent models. However, their cellular targets and underlying mechanisms have remained elusive. We found that dietary sulindac induced apoptosis to remove the intestinal stem cells with nuclear or phosphorylated ?-catenin in ...
Epidemiological and animal studies suggest that tea may be protective towards cancers of the GI tract. White tea, the least processed form of tea, contains high levels of polyphenols and, like green tea, is chemopreventive towards heterocyclic amine-initiated colonic aberrant crypt formation in male F344 rats. We examined for the first time the relative effectiveness of white ...
The non-steroidal anti-inflammatory drug (NSAID) sulindac exhibits cyclooxygenase (COX)-dependent and COX-independent chemopreventive properties in human cancer. The present study was aimed at investigating whether the hydroxamic acid substitution for the carboxylic acid group could enhance the in vitro antitumor and antiangiogenic activities of ...
Recent evidence suggests that nonsteroidal antiinflammatory drugs (NSAIDs) may prevent colorectal cancer. The mechanism of action of NSAIDs in chemoprevention is unknown but may be linked to their effect on mucosal prostaglandin levels. Levels of five major prostaglandin metabolites were measured by gas chromatography�mass spectrometry in biopsy specimens of flat rectal ...
BackgroundFamilial adenomatous polyposis is caused by a germ-line mutation in the adenomatous polyposis coli gene and is characterized by the development of hundreds of colorectal adenomas and, eventually, colorectal cancer. Nonsteroidal antiinflammatory drugs can cause regression of adenomas, but whether they can prevent adenomas is unknown.MethodsWe conducted a randomized, double-blind, ...
EP4 expression in human glioblastoma cells correlates with growth on soft agar. The cyclooxygenase (COX) inhibitor, sulindac sulfide, first altered specificity protein-1 (Sp-1) and, early growth response gene-1 (Egr1) expression, then increased the expression of nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) and activating transcription factor-3 (ATF3), and then ...
The nonsteroidal anti-inflammatory drug (NSAID) sulindac and the ornithine decarboxylase (ODC) antagonist difluoromethylornithine (DFMO), individually and together, are effective inhibitors of colon carcinogenesis. However, chronic use of sulindac is associated with significant side effects. We evaluated the chemopreventive efficacy of ...
PurposeNonsteroidal anti-inflammatory drugs (NSAIDs) are promising chemopreventive agents against colon and other cancers. However the molecular basis mediated by NSAIDs for chemoprevention has not been fully elucidated. Environmental carcinogens induce DNA mutation and cellular transformation; therefore, we examined the effect of NSAIDs on carcinogenesis ...
One of the approaches in chemoprevention to prevent or delay the progression of precancerous lesions, is to apply chemopreventive agents that can potentially block angiogenesis. A quantitative in vivo angiogenesis inhibition assay was developed to test the efficacy of twelve chemopreventive agents that represent different chemical ...
Sulindac, atorvastatin, or prebiotic dietary fiber may reduce colorectal cancer (CRC) risk. However, clinical trial data are currently limited. We conducted a randomized, phase II chemoprevention trial involving subjects 40 years or older, with previously resected colon cancer or multiple/advanced colorectal adenomas. Magnification chromoendoscopy (MCE) ...
a friend Share Sulindac is a nonsteroidal anti-inflammatory drug (NSAID). It is used to relief pain and swelling associated with certain types of arthritis. Sulindac overdose...
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Curcumin exhibits anti-inflammatory and antitumor activity and is being tested in clinical trials as a chemopreventive agent for colon cancer. Curcumin's chemopreventive activity was tested in a transgenic mouse model of lung cancer that expresses the human Ki-rasG12C allele in a doxycycline (DOX) inducible and lung-specific manner. ...
Epidemiological studies link increased garlic (Allium sativum) consumption with a reduced incidence of colon cancer in various human populations. Experimental carcinogenesis studies in animal models and in cell culture systems indicate that several allium-derived compounds exhibit inhibitory effects and that the underlying mechanisms may involve both the initiation and promotion phases of ...
Chemopreventive agents generate oxidative stress, which culminates in cell death and may be part of a general mechanism of chemoprevention. The redox-responsive cyclooxygenase (COX)-2, overexpressed during carcinogenesis, has been a target for cancer prevention. To assess the potential link between chemopreventive agents, oxidative ...
Some recent studies of the effects of chemopreventive agents have begun to use new rodent models to improve the analysis of stages of colonic preneoplasia, and how chemopreventive agents modify progressive abnormal cell development. In one of the models of inherited predisposition to colon cancer, mice carrying a truncated Apc allele with a nonsense ...
The antitumor effects of nonsteroidal anti-inflammatory drugs (NSAID) are assumed to be due to the inhibition of COX activity, but COX-independent mechanisms may also play an important role. NSAID-activated gene (NAG-1/GDF15) is induced by NSAIDs and has antitumorigenic activities. To determine the contribution of COX-2 inhibition and NAG-1/GDF15 expression to the prevention of colon ...
Nonsteroidal anti-inflammatory drugs (NSAID) display promising antineoplastic activity, but toxicity resulting from cyclooxygenase (COX) inhibition limits their clinical use for chemoprevention. Studies suggest that the mechanism may be COX independent, although alternative targets have not been well defined. Here, we show that the NSAID sulindac sulfide ...
often than prescribed by your doctor. Sulindac helps control arthritis pain but does not cure arthritis. If you are taking sulindac to treat arthritis pain, it may take 1 week or...
A 44 year old female, previously on propranolol, phenytoin and phenobarbital, developed hepatotoxicity while on sulindac and acetaminophen containing analgesic. A limited review of hepatotoxicity and drug interactions of sulindac is presented. The possible mechanism of hepatotoxicity and its treatment is suggested. PMID:3903180
... and γ gene expression and activates JNK kinase (1,2). Similarly, Sulindac ... interference with NF-κB and the pathways regulated by Sulindac may ...
DTIC Science & Technology
Nonsteroidal anti-inflammatory drugs (NSAID) such as sulindac sulfide (SS) display promising antineoplastic properties, but toxicities resulting from COX inhibition limit their clinical use. Although COX inhibition is responsible for the anti-inflammatory activity of SS, recent studies suggest that phosphodiesterase (PDE) 5 inhibition and activation of cyclic guanosine ...
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to have chemopreventive activity, but the mechanisms involved are not clearly understood. Although NSAIDs inhibit cyclooxygenase activity, they also increase the expression of a divergent member of the transforming growth factor-beta superfamily, termed NSAID-activated gene 1 (NAG-1), a protein with an ...
Purpose of reviewThe deciphering of the human genome sequence has enabled the identification of genetic polymorphisms that are responsible for inter-individual variation in the response to drug therapy. This field is referred to as pharmacogenetics. We review the impact of pharmacogenetics on therapy in diseases of the colon using three common variant enzyme systems as examples.Recent findingsMany ...
Increased polyamine synthesis and inflammation have long been associated with colon carcinogenesis in both preclinical models and in humans. Recent experimental studies suggest that polyamines may be mechanistically involved in colonic inflammatory processes. Genetic epidemiology results indicate that a single nucleotide polymorphism influencing the expression of a polyamine biosynthetic gene is ...
... TITLE: Polyphenols and Prostate Cancer Chemoprevention ... 5. FUNDING NUMBERS Polyphenols and Prostate Cancer Chemoprevention ...
The effects of arsenic trioxide (ATO) in combination with sulindac (SUL), sulindac sulfide (SS) or sulindac sulfone (SF) on human (Jurkat, HL-60, K562 and HPB-ALL) and mouse (EL-4) leukemic cell lines were investigated. The cells showed different sensitivity to sulindacs (2.5-200 ?M) with SS being the most ...
Hypoxic-ischemia injury occurs after trauma causes consequential bone necrosis. Non-steroid anti-inflammatory drugs (NSAIDs) are frequently used in orthopedic clinics for pain relief. However, the underlying mechanism and outcome for usage of NSAIDs is poorly understood. To investigate the damage and loss of osteoblast function in hypoxia, two hypoxia mimetics, cobalt chloride (CoCl(2) ) and ...
Sulindac, the non-steroidal anti-inflammatory drug has shown promise in the prevention of colon cancer but the molecular mechanisms by which it mediates such effects remain to be elucidated. Sulindac sulfide is the major active metabolite of sulindac and believed to be responsible for mediating the effects of ...
Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti-inflammatory effects and have been shown to have chemopreventive effects as well. NSAIDs inhibit cyclooxygenase (COX) activity to exert their anti-inflammatory effects, but it is not clear whether their antitumorigenic ability is through COX inhibition. Using subtractive hybridization, we previously ...
Sulindac is a nonsteroidal, anti-inflammatory drug (NSAID) that has also been studied for its anticancer activity. Recent studies suggest that sulindac and its metabolites act by sensitizing cancer cells to oxidizing agents and drugs that affect mitochondrial function, resulting in the production of reactive oxygen species and death by apoptosis. In ...
Epidemiological studies suggest that nonsteroidal anti-inflammatory agents decrease the risk of colorectal cancer. This is believed to be mediated, at least in part, by inhibition of cyclooxygenase (COX) activity. There are two COX isoenzymes, namely the constitutively expressed COX-1 and the inducible COX-2. COX-2 is overexpressed in adenomas and colorectal cancers, and COX-2-specific inhibitors ...
... chemopreventive drugs (chemopreventive drugs are compounds ... to prevent breast cancer, ie tamoxifen ... mammary tumor development, growth, and ...
