Ginsenoside Rh2 sensitizes the anti-cancer effects of sunitinib by inducing cell cycle arrest in renal cell carcinoma

Abstract

Sunitinib, a VEGF blockade, is used to treat clear cell renal cell carcinoma (ccRCC). However, the anti-cancer treatment effects of sunitinib do not last long in ccRCC patients. Ginsenoside, a natural medicine extracted from ginseng, has been studied in cancer treatment and shown to have anti-tumor effects and low toxicity. We assessed cell viability and cell cycle analysis in ccRCC cell lines after treatment with ginsenoside and sunitinib. DNA damage was evaluated by measuring 8-OHdG levels and comet assay. ROS levels, reflecting the cause of oxidative stress, were also measured. Ginsenoside significantly enhanced the inhibition of cell viability by sunitinib, a result that was also confirmed in the xenograft model. In cell cycle analysis, combination treatment of ginsenoside and sunitinib enhanced G2M arrest in comparison with single-treatment groups. In addition, DNA damage was increased by ginsenoside and sunitinib according to the comet assay, and the level of 8-OHdG, which reflects oxidative DNA damage, also increased. We verified that ginsenoside enhances the efficacy of sunitinib to inhibit the proliferation of ccRCC cells via induction of oxidative DNA damage. The combination therapy of sunitinib and ginsenoside suggested the possibility of effectively treating ccRCC patients.