Conjugated linoleic acid induces apoptosis of murine mammary tumor cells via Bcl-2 loss.

Abstract

Conjugated linoleic acid (CLA) is a powerful anticancer agent in a number of tumor model systems; however, its precise mechanism of action remains elusive. Here, we report that t10,c12 CLA, a component of synthetic CLA supplements, induced apoptosis and G1 arrest of p53 mutant TM4t murine mammary tumor cells. Furthermore, t10,c12-CLA induced a time- and concentration-dependent cleavage of caspases-3 and -9, and release of cytochrome c from mitochondria to cytosol. Levels of Bcl-2 protein were decreased both in total cellular lysates and in mitochondria after t10,c12-CLA treatment; however, there was no significant change in Bax or Bak. Overexpression of Bcl-2 attenuated apoptosis in response to t10,c12-CLA treatment. These results demonstrate that t10,c12-CLA triggers apoptosis of p53 mutant murine mammary tumor cells through the mitochondrial pathway by targeting Bcl-2.

• Authors: Lihui Ou, Clement Ip, Barbara Lisafeld, Margot M Ip
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 356 Issue 4 Pg. 1044-9 (May 18 2007) ISSN: 0006-291X [Print] United States
• PMID: 17400188 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• Linoleic Acid

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Apoptosis (drug effects)
• Cell Line
• Dose-Response Relationship, Drug
• Linoleic Acid (administration & dosage)
• Mammary Neoplasms, Experimental (metabolism, pathology)
• Mice
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Tumor Suppressor Protein p53 (metabolism)