Ginsenoside 20(S)-Rg3 suppresses ovarian cancer migration via hypoxia-inducible factor 1 alpha and nuclear factor-kappa B signals

Hypoxia-inducible factor 1 is believed to play a prominent role in the survival and developing progress of cancers. As a result, inhibiting subunit of hypoxia-inducible factor 1 represents an attractive strategy against tumor. Although hypoxia-inducible factor 1 is a hypoxia-regulated subunit, increasing evidence indicates that hypoxia-inducible factor 1 could stable expression under normoxic conditions, regulated by non-hypoxia-mediated mechanisms. However, there are few strategies to target hypoxia-inducible factor 1 under normoxic conditions. Here, we report that ginsenoside 20(S)-Rg3, one of the main active ingredients in red ginseng, restrains hypoxia-inducible factor 1 expression under normal oxygen levels in human ovarian cancer cell lines, SKOV3 and 3AO, which leads to potently inhibits migration of ovarian cancer in vitro and in vivo. 20(S)-Rg3 could decrease the expression of hypoxia-inducible factor 1 by upregulation of prolyl hydroxylase domain protein 1 to promoting hypoxia-inducible factor 1 ubiquitin-proteasome degradation under normal oxygen levels. Furthermore, 20(S)-Rg3 could attenuate the expression of nuclear factor- B, which may be another possible mechanism for 20(S)-Rg3 to block ovarian cancer migration. Taken together, our study suggests that 20(S)-Rg3 is a strong inhibitor of hypoxia-inducible factor 1, which may provide a novel agent for future treatments for ovarian cancer.