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- Title
Both PPARγ and PPARδ influence sulindac sulfide-mediated p21<sup>WAF1/CIP1</sup> upregulation in a human prostate epithelial cell line.
- Authors
Jarvis, Morag C.; Gray, Tim J. B.; Palmer, Colin N. A.
- 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 PPARγ agonist and a PPARδ antagonist in an immortalized prostatic epithelial cell line (PNT1A). We utilized siRNA technology to show that PPARγ is required for both growth inhibition and p21WAF1/CIP1 upregulation in response to sulindac sulfide treatment in PNT1A cells. In addition, the overexpression of PPARδ 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 PPARγ/PPARδ/p21WAF1/CIP1 and the cancer chemo-preventative properties of NSAIDs.Oncogene (2005) 24, 8211–8215. doi:10.1038/sj.onc.1208983; published online 8 August 2005
- Subjects
SULINDAC; NONSTEROIDAL anti-inflammatory agents; EPITHELIAL cells; CELL lines; THERAPEUTICS; BIOCHEMISTRY
- Publication
Oncogene, 2005, Vol 24, Issue 55, p8211
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1208983