1. Cyclic phosphatidic acid decreases proliferation and survival of colon cancer cells by inhibiting peroxisome proliferator-activated receptor γ
- Author
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Kimiko Murakami-Murofushi, Tamotsu Tsukahara, Shuwa Hanazawa, Yoshiki Iwamoto, and Tetsuyuki Kobayashi
- Subjects
medicine.medical_specialty ,Cell type ,Cell Survival ,Physiology ,Phosphatidic Acids ,Peroxisome proliferator-activated receptor ,Biology ,Biochemistry ,Heterocyclic Compounds, 1-Ring ,chemistry.chemical_compound ,Cell Line, Tumor ,Internal medicine ,Lysophosphatidic acid ,medicine ,Humans ,heterocyclic compounds ,Receptor ,Cell Proliferation ,Pharmacology ,chemistry.chemical_classification ,Cell growth ,DNA ,Cell Biology ,Phosphatidic acid ,Peroxisome ,PPAR gamma ,Endocrinology ,chemistry ,Nuclear receptor ,Colonic Neoplasms ,cardiovascular system ,Cancer research ,Lysophospholipids ,HT29 Cells - 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.
- Published
- 2010