t,t-Conjugated linoleic acid (CLA) isomers reported to exert antitumor effects by inducing apoptosis. However, the precise mechanism underlying remains unclear. Restoration of reduced gap junctional intercellular communication (GJIC) in cancer cells inhibits cell growth by apoptosis. We hypothesized, t,t-CLA might cause apoptosis with enhanced GJIC in MCF-7 cells. Growth inhibitory effects of t9,t11-and t10,t12-CLA were investigated with reference to t10,c12-CLA,which is equally effective with c9,t11-CLA. Results demonstrated, t,t-CLA inhibited cell growth with cell shrinkage, nuclear condensation, increased cell population in sub-G1 phase in cell cycle and elevated caspase-3 which indicate apoptosis. It enhanced GJIC with increased connexin43 (Cx43) at the mRNA and protein levels with higher efficacy as compared to t10,c12-CLA but t9,t11-CLA is superior to t10,t12-CLA. Findings suggest, the growth inhibitory effect of t,t-CLA isomers might be associated with the up-regulation of Cx43, which enhances GJIC in MCF-7 cells. t,t-CLAs inhibited nuclear factor- κB (NF-κB) translocation and increased reactive oxygen species (ROS) generation which might trigger up-regulation of Cx43 and restore GJIC.

Keywords: t,t-CLA, Apoptosis,Cx43, GJIC, ROS.

Citation Format: Yeong Lae Ha, Abdur Rakib, Jeong O. Kim. trans,trans-Conjugated linoleic acid induces apoptosis by enhancing gap junctional intercellular communication inhuman breast cancer MCF-7 cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-A02.

©2015 American Association for Cancer Research.
2015