Auranofin, an inhibitor of thioredoxin reductase, induces apoptosis in hepatocellular carcinoma Hep3B cells by generation of reactive oxygen species

• DOI: 10.4149/gpb_2016043
• Publication Date: 2017-05-15T08:33:28Z
• Authors: Hyun Hwang-Bo; Jin-Woo Jeong; Min Ho Han; Cheol Park; Su-Hyun Hong; Gi-Young Kim; Sung-Kwon Moon; Jaehun Cheong; Wun-Jae Kim; Young Hyun Yoo; Yung Hyun Choi
• Keywords: Auranofin; Inhibitor of apoptosis; Intrinsic apoptosis

Mammalian thioredoxin reductase (TrxR) plays a vital role in restoring cellular redox balance disrupted by reactive oxygen species (ROS) generation and oxidative damage. Here, we evaluated whether auranofin, selective inhibitor of TrxR, could serve as potential anti-cancer agent through its targeting TrxR activity Hep3B hepatocellular carcinoma cells. Auranofin treatment reduced the these cells induced apoptosis, which were accompanied up-regulation death receptors (DRs) activation caspases, well promotion proteolytic degradation poly(ADP-ribose)-polymerase. Treatment with pan-caspase reversed auranofin-induced apoptosis growth suppression, indicating that auranofin may induce caspase-dependent mechanism involving both intrinsic extrinsic apoptotic pathways. also significantly altered mitochondrial function, promoting membrane permeabilization cytochrome c release regulating Bcl-2 family proteins; events an accumulation ROS. Inhibition ROS quencher attenuated inactivation auranofin-treated almost completely suppressed DRs thereby preventing loss cell viability. Taken together, findings indicate inhibition activates ROS- signaling pathways triggers cancer death.