Peroxisome proliferator-activated receptor δ confers resistance to peroxisome proliferator-activated receptor γ-induced apoptosis in colorectal cancer cells

D. Wang, W. Ning, D. Xie, L. Guo, R. N. Dubois

    Research output: Contribution to journalArticle

    21 Scopus citations

    Abstract

    Peroxisome proliferator-activated receptor γ (PPARγ) may serve as a useful target for drug development in non-diabetic diseases. However, some colorectal cancer cells are resistant to PPARγ agonists by mechanisms that are poorly understood. Here, we provide the first evidence that elevated PPARδ expression and/or activation of PPARδ antagonize the ability of PPARγ to induce colorectal carcinoma cell death. More importantly, the opposing effects of PPARδ and PPARγ in regulating programmed cell death are mediated by survivin and caspase-3. We found that activation of PPARγ results in decreased survivin expression and increased caspase-3 activity, whereas activation of PPARδ counteracts these effects. Our findings suggest that PPARδ and PPARγ coordinately regulate cancer cell fate by controlling the balance between the cell death and survival and demonstrate that inhibition of PPARδ can reprogram PPARγ ligand-resistant cells to respond to PPARγ agonists.

    Original languageEnglish (US)
    Pages (from-to)1013-1023
    Number of pages11
    JournalOncogene
    Volume31
    Issue number8
    DOIs
    StatePublished - Feb 23 2012

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    Keywords

    • apoptosis
    • colorectal cancer
    • peroxisome proliferator-activated receptors
    • survivin

    ASJC Scopus subject areas

    • Molecular Biology
    • Genetics
    • Cancer Research

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