Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line.

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Jarvis MC, Gray TJ, Palmer CN

Both PPARgamma and PPARdelta influence sulindac sulfide-mediated p21WAF1/CIP1 upregulation in a human prostate epithelial cell line.

Oncogene. 2005 Dec 8;24(55):8211-5.

PubMed ID

16091736 [ View in PubMed

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Abstract

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 cyclin-dependent kinase inhibitor p21WAF1/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 PPARgamma agonist and a PPARdelta antagonist in an immortalized prostatic epithelial cell line (PNT1A). We utilized siRNA technology to show that PPARgamma is required for both growth inhibition and p21WAF1/CIP1 upregulation in response to sulindac sulfide treatment in PNT1A cells. In addition, the overexpression of PPARdelta partially rescued these cells from growth inhibition and also dramatically inhibited sulindac sulfide-mediated p21WAF1/CIP1 upregulation. Together these data identify a novel link between PPARgamma/PPARdelta/p21WAF1/CIP1 and the cancer chemo-preventative properties of NSAIDs.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Sulindac	Peroxisome proliferator-activated receptor delta	Protein	Humans	Unknown	Negative modulator	Details