Cyclic phosphatidic acid decreases proliferation and survival of colon cancer cells by inhibiting peroxisome proliferator‐activated receptor γ

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. This work was supported by Grants‐in‐Aid for Scientific Research (C) 22591482 (to Tamotsu Tsukahara) from the Japan Society for the Promotion of Science (JSPS), and supported in part by the American Heart Association Grant 0525489B (to Tamotsu Tsukahara).