Sub-toxic dose of apigenin sensitizes HepG2 cells to TRAIL through ERK-dependent up-regulation of TRAIL receptor DR5.

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is regarded as a promising candidate for anticancer therapy due to its selective toxicity to cancer cells. Nevertheless, because of TRAIL resistance in some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In this study, we investigated the underlying mechanism of apigenin-induced sensitization of HepG2 cells to TRAIL-induced cell death. Synergistic induction of apoptosis by combination was confirmed by examining the typical morphology changes of apoptosis, PARP-cleavage, and activation of effector caspases. Z-VAD-fmk, a pan-caspase inhibitor, inhibited the enhanced cell death by combined treatment of apigenin and TRAIL, demonstrating that a caspase-dependent pa

SUBMITTER: Kim EY 

PROVIDER: S-EPMC3887848 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature