Ginsenoside Rh(2) enhances antitumour activity and decreases genotoxic effect of cyclophosphamide

Ginsenoside Rh(2), a panaxadiol saponins, possesses various antitumour properties. Cyclophosphamide, an alkylating agent, has been shown to possess various genotoxic and carcinogenic effects, however, it is still used extensively as an antitumour agent and immunosuppressant in the clinic. Previous reports reveal that cyclophosphamide is involved in some secondary neoplasms. In this study, the antitumour activity and genotoxic effect of oral intake of ginsenoside Rh(2) combined with intraperitoneal injection of cyclophosphamide was investigated. Meanwhile, C57BL/6 mice bearing B16 melanoma and Lewis lung carcinoma cells were respectively used to estimate the antitumour activity in vivo. The clastogenic activity in bone marrow polychromatic erythrocytes was assayed by frequency of micronucleus. The DNA damage in peripheral white blood cells was assayed by single cell gel electrophoresis as well. The results indicated that oral administration of Rh(2) (5, 10 and 20 mg/kg body weight) alone has no obvious antitumour activity and genotoxic effect in mice, while Rh(2) synergistically enhanced the antitumour activity of cyclophosphamide (40 mg/kg body weight) in a dose-dependent manner. Rh(2) decreased the micronucleus formation in polychromatic erythrocytes and DNA strand breaks in white blood cells in a dose-dependent way. Our results suggest that ginsenoside Rh(2) is able to enhance the antitumour activity and decrease the genotoxic effect of cyclophosphamide.