OSU-CG5, a novel energy restriction mimetic agent, targets human colorectal cancer cells in vitro.

ABSTRACT: Energy-restriction mimetic agents (ERMAs) are small-molecule agents that target various aspects of energy metabolism, which has emerged as a promising approach in cancer therapy. In the current study, we tested the ability of OSU-CG5, a novel ERMA, to target human colorectal cancer (CRC) in vitro.Two human CRC cell lines (HCT-116 and Caco-2) were tested. Cell viability was assessed using MTT assay. Caspase-3/7 activities were measured using Caspase-Glo 3/7 assay kit. Western blot analysis was used to measure the expression of relevant proteins in the cells. Glucose consumption of the cells was detected using glucose uptake cell-based assay kit.OSU-CG5 dose-dependently inhibited HCT-116 and Caco-2 cell proliferation with the IC?? values of 3.9 and 4.6 ?mol/L, respectively, which were 20-25-fold lower than those of resveratrol, a reference ERMA. Both OSU-CG5 (5, 10, and 20 ?mol/L) and resveratrol (50, 100, and 200 ?mol/L) dose-dependently increased caspase-3/7 activity and PARP level in the cells. Furthermore, both OSU-CG5 and resveratrol induced dose-dependent energy restriction in the cells: they suppressed glucose uptake and Akt phosphorylation, decreased the levels of p-mTOR and p-p70S6K, increased the levels of ER stress response proteins GRP78 and GADD153, and increased the level of ?-TrCP, which led to the downregulation of cyclin D1 and Sp1.OSU-CG5 exhibits promising anti-cancer activity against human CRC cells in vitro, which was, at least in part, due to energy restriction and the consequent induction of ER stress and apoptosis.

SUBMITTER: Arafa el-SA 

PROVIDER: S-EPMC4647897 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature