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  • Title: Cyclic phosphatidic acid decreases proliferation and survival of colon cancer cells by inhibiting peroxisome proliferator-activated receptor γ.
    Author: Tsukahara T, Hanazawa S, Kobayashi T, Iwamoto Y, Murakami-Murofushi K.
    Journal: Prostaglandins Other Lipid Mediat; 2010 Nov; 93(3-4):126-33. PubMed ID: 20932931.
    Abstract:
    Cyclic phosphatidic acid (cPA), a structural analog of lysophosphatidic acid (LPA), is one of the simplest phospholipids found in every cell type. cPA is a specific, high-affinity antagonist of peroxisome proliferator-activated receptor gamma (PPARγ); however, the molecular mechanism by which cPA inhibits cellular proliferation remains to be clarified. In this study, we found that inhibition of PPARγ prevents proliferation of human colon cancer HT-29 cells. cPA suppressed cell growth, and this effect was reversed by the addition of a PPARγ agonist. These results indicate that the physiological effects of cPA are partly due to PPARγ inhibition. Our results identify PPARγ as a molecular mediator of cPA activity in HT-29 cells, and suggest that cPA and the PPARγ pathway might be therapeutic targets in the treatment of colon cancer.
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