Enhancement of carcinogenesis by prostaglandins

Lupulescu, A.

doi:10.1038/272634a0

Cited by 89 publications

(21 citation statements)

References 8 publications

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“…NSAIDs block the enzyme cyclooxygenase and in turn inhibit prostaglandin biosynthesis. Prostaglandins may serve as cofactors in carcinogenesis with potential effects ranging from direct mutagenesis to tumour promotion and immune suppression (Lupulescu, 1978;Mellemkjaer et al, 1996). One study (McCormick and Wilson, 1986) suggests that the cancer inhibitory effects of NSAIDs may be independent of their effects on prostaglandin synthesis.…”

Section: Discussionmentioning

confidence: 99%

Breast cancer and NSAID use: a meta-analysis

2001

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Recent epidemiological studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of several cancers including breast cancer. This meta-analysis examined the studies on NSAID use and breast cancer. The estimators of relative risk and associated variances, which have been adjusted for the greatest number of confounders, were abstracted and included in the meta-analysis. Combined estimators of relative risk (RR) were calculated using either fixed or random effect models. Meta-analyses were performed on 6 cohort studies (number of cases ranged from 14 to 2414) and 8 case–control studies (number of cases ranged from 252 to 5882). The combined estimate of relative risk was 0.82 (95% confidence interval [CI] = 0.75–0.89). The combined estimate for cohort studies was 0.78 (95% CI = 0.62–0.99) and was 0.87 (95% CI = 0.84–0.91) for case–control studies. The findings of this meta-analysis suggest that NSAID use may be associated with a small decrease in the risk of breast cancer. However, the available data are insufficient to estimate the dose–response effect for duration and frequency of use of any particular types of NSAID. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Section: Discussionmentioning

confidence: 99%

Breast cancer and NSAID use: a meta-analysis

2001

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“…Experimental studies have shown inhibition of colorectal cancer and adenomas (97)(98)(99)(100), possibly due to inhibition of the enzyme cyclooxygenase, which controls synthesis of prostaglandins that may increase cell proliferation and tumor growth (101)(102)(103)(104). Case-reports (105)(106)(107) and two randomized trials (86,87) suggested that the NSAID sulindac caused reduction of the number and size of colorectal polyps in patients with familial adenomatous polyposis.…”

Section: Promoters and Protective Agentsmentioning

confidence: 99%

Nonhormonal drugs and cancer.

Stolley

Zahm

1995

Environ Health Perspect

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Nonhormonal drugs probably account for only a small proportion of human cancer but have contributed many valuable insights into carcinogenic mechanisms. The antineoplastics, radiopharmaceuticals, and a few other agents account for most of the known drug-induced cancer. A number of other agents are under suspicion, usually due to studies in laboratory animals or to preliminary clinical or epidemiologic observations. This group includes some drugs in widespread use such as clofibrate and cimetidine. For a few drugs that are carcinogenic in animals, such as dapsone and isoniazid, epidemiologic studies have shown little to no evidence of carcinogenicity. Recent experimental studies have shown tumor promotion by the commonly used antidepressants amitriptyline and fluoxetine and some antihistamines, which deserve epidemiologic investigation of cancer risk. Some drugs may also protect against cancer, as suggested by the lower risk of colorectal cancer among regular users of nonsteroidal antiinflammatory drugs. Pharmacoepidemiologic studies must take into account possible confounding by the original conditions for which drugs were taken and the typically long latency period of drug-induced cancer. Improved postmarketing surveillance, continued routine case-control surveillance, and ad hoc case-control and cohort studies are needed to evaluate drugs already in use as well as newly introduced agents. -Environ Health Perspect 103 (Suppl 8):191-196 (1995)

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“…COX enzymes are responsible for mediating the conversion of arachidonic acid into prostaglandins. Since particular types of prostaglandins have been shown to promote carcinogenesis (Lupulescu, 1978) it seemed logical that this hypothesis was correct. However, it has since been shown that NSAIDs can inhibit growth and cause the death of cells not expressing COX enzymes (Hanif et al, 1996).…”

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confidence: 99%

Both PPARγ and PPARδ influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line

2005

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Nonsteroidal anti-inflammatory drugs (NSAIDs) including sulindac sulfide are known to exert cancer chemopreventative activity in a range of cell lines. This activity has been shown to involve the upregulation of the cyclindependent kinase inhibitor p21 WAF1/CIP1 . It is also known that NSAIDs can act as peroxisome proliferator-activated receptor (PPAR) agonists and antagonists. In this study, we show that sulindac sulfide acts both as a PPARc agonist and a PPARd antagonist in an immortalized prostatic epithelial cell line (PNT1A). We utilized siRNA technology to show that PPARc is required for both growth inhibition and p21 WAF1/CIP1 upregulation in response to sulindac sulfide treatment in PNT1A cells. In addition, the overexpression of PPARd partially rescued these cells from growth inhibition and also dramatically inhibited sulindac sulfide-mediated p21 WAF1/CIP1 upregulation. Together these data identify a novel link between PPARc/ PPARd/p21 WAF1/CIP1 and the cancer chemo-preventative properties of NSAIDs.

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Enhancement of carcinogenesis by prostaglandins

Cited by 89 publications

References 8 publications

Breast cancer and NSAID use: a meta-analysis

Breast cancer and NSAID use: a meta-analysis

Nonhormonal drugs and cancer.

Both PPARγ and PPARδ influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line

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