OSW-1 inhibits tumor cell proliferation and migration via uncoupling protein 2 in hepatocellular carcinoma

Apoptosis is one of the primary mechanisms by which Anticancer drugs exert their effects. Orsaponin (OSW-1) is a natural broad-spectrum inhibitor of Enterovirus replication isolated from Ornithogalum saundersiae. It is a specific antagonist of cholesterol-binding protein (OSBP) and OSBP-related protein 4 (ORP4). OSW-1 exhibits antitumor activity; however, its mechanism remains to be elucidated. The present study aimed to explore the cytotoxicity of OSW-1 in hepatocellular carcinoma (HCC) and its antitumor mechanisms. Gene Expression Profiling Interactive Analysis database analysis showed that uncoupling protein 2 (UCP2) expression was markedly higher in HCC tissue. Mitochondrial membrane potential and cell cycle progression in Hep3B cells were assessed by flow cytometry using JC-1 and propidium iodide staining, respectively. OSW-1 decreased mitochondrial membrane potential, induced cell cycle arrest at the G₂/M phase and caused production of intracellular Reactive Oxygen Species. Western blot and quantitative PCR determined that OSW-1 induced Apoptosis in Hep3B cells by downregulating UCP2 expression. These results suggest that OSW-1 has potential as a therapeutic agent for liver Cancer. Future studies should explore its effects on a broader range of HCC cell lines and in vivo models and investigate its molecular mechanisms and side effects.

UCP2; apoptosis; hepatocellular carcinoma; mitochondrial dysfunction; reactive oxygen species.