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

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.

• Authors: Tamotsu Tsukahara, Shuwa Hanazawa, Tetsuyuki Kobayashi, Yoshiki Iwamoto, Kimiko Murakami-Murofushi
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 93 Issue 3-4 Pg. 126-33 (Nov 2010) ISSN: 1098-8823 [Print] United States
• PMID: 20932931 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Inc. All rights reserved.

Chemical References

• Heterocyclic Compounds, 1-Ring
• Lysophospholipids
• PPAR gamma
• Phosphatidic Acids
• DNA

Topics

• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Colonic Neoplasms (pathology)
• DNA (metabolism)
• HT29 Cells
• Heterocyclic Compounds, 1-Ring (pharmacology)
• Humans
• Lysophospholipids (pharmacology)
• PPAR gamma (antagonists & inhibitors, metabolism)
• Phosphatidic Acids (pharmacology)