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

Morag C. Jarvis, Tim J.B. Gray, Colin N.A. Palmer (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)8211-8215
    Number of pages5
    JournalOncogene
    Volume24
    Issue number55
    Early online date8 Aug 2005
    DOIs
    Publication statusPublished - 8 Dec 2005

    Keywords

    • NSAIDs
    • p21
    • PPARγ
    • PPARδ
    • Prostate cancer

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