title: ATF3 Mediates Anti-Cancer Activity of Trans-10, cis-12-Conjugated Linoleic Acid in Human Colon Cancer Cells.
abstract: Conjugated linoleic acids (CLA) are a family of isomers of linoleic acid. CLA increases growth arrest and apoptosis of human colorectal cancer cells through an isomer-specific manner. ATF3 belongs to the ATF/CREB family of transcription factors and is associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which t10, c12-CLA stimulates ATF3 expression and apoptosis in human colorectal cancer cells. t10, c12-CLA increased an apoptosis in human colorectal cancer cells in dose dependent manner. t10, c12-CLA induced 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. t10, c12-CLA increases GSK3β expression and suppresses IGF-1-stimulated phosphorylation of Akt. The knockdown of ATF3 suppressed expression of GSK3β and NAG-1 and PARP cleavage. The results suggest that t10, c12-CLA induces apoptosis through ATF3-mediated pathway in human colorectal cancer cells.
authors.affiliation: Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Kui-Jin
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Jihye
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Food Science, University of Massachusetts, Amherst, MA, 01003, USA.
authors.forename: Yeonhwa
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, MD, 20742, USA.
authors.forename: Seong-Ho
authors.initials: SH
authors.lastname: Lee
keywords: Activating transcription factor 3; Colon cancer; Conjugated linoleic acid