Ginsenoside Rh2 inhibits HeLa cell energy metabolism and induces apoptosis by upregulating voltage-dependent anion channel 1

20(S)-Ginsenoside Rh2 [20(S)-GRh2], one of the main active components of Panaxginseng, induces apoptosis in a wide range of cancer cell types. The present study found that 20(S)-GRh2 reduces mitochondrial membrane potential, decreases adenosine triphosphate generation and induces reactive oxygen species in HeLa cervical cancer cells. In addition, 20(S)-GRh2 activated mitochondrion-dependent apoptosis and inhibited both mitochondrial oxidative phosphorylation and glycolysis in HeLa cells. It was found that voltage-dependent anion channel 1 (VDAC1) expression was significantly upregulated by 20(S)-GRh2 treatment, while hexokinase 2 expression was downregulated and segregated from the mitochondria. Furthermore, 20(S)-GRh2 promoted Bax transport from the cytoplasm to the mitochondria, and knockdown of VDAC1 inhibited Bax transport and apoptosis. These results suggest that VDAC1 is a novel target of 20(S)-GRh2. The present study provides a better understanding of the mechanistic link between cervical cancer metabolism and growth control, and these results may facilitate the development of new treatments for cervical cancer.