International Journal of Food and Nutritional Science | 2015-05-01

ATF3 mediates anti-cancer activity of trans-10, cis-12-conjugated linoleic acid in human colon cancer cells

Seong-Ho Lee

Abstract

Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid found mostly in the meat and dairy products. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. The trans10, cis12-CLA (t10, c12-CLA) increased expression of NSAIDs-activated gene-1 (NAG-1) through activating the transcription factor 3 (ATF3)-mediated pathway. ATF3 belong to the ATF/CREB family of transcription factors and ATF3 gene expression is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism of how t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased ATF3 mRNA and luciferase activity of ATF3 promoter in a dose-dependent manner. The responsible region for ATF3 transcriptional activation by t10, c12-CLA is located between -147 and -1850 of ATF3 promoter. mRNA stability of ATF3 was not affected by t10, c12-CLA treatment. The treatment of t10, c12-CLA increases expression of GSK3β and suppresses IGF-1-stimulated phosphorylation of Akt. The knockdown of ATF3 suppressed expression of GSK3β and NAG-1 and poly ADP ribose polymerase (PARP) cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3/GSK3β/NAG-1-mediated pathway in in human colorectal cancer cells.

Keywords: conjugated linoleic acid, CLA, ATF3, apoptosis, colon cancer