ROS attenuates the antitumor effect of Raddeanin on ovarian cancer cells Skov3.

Epithelial ovarian cancer is the fourth commonest cause of female cancer death, but no proper evidence had proved that surgery could prolong the survival time. Hence, new effective chemotherapy is necessary to improve the survival. Raddeanin A (RA), anoleanane-type triterpenoid sponin, is isolated from Anemone raddeana. Previous study had proved that RA exerted antitumor activity through inhibiting proliferation and promoting apoptosis of some kinds of cancer cell. ROS is a double-edged sword for tumors and might contribute to therapy resistant. In this study, we discuss at the first time whether ROS was involved in the antitumor effect of RA on Skov3 cells, and analysis the mechanism. The results showed that after be treated by RA, the proliferation of Skov3 was inhibited, and this effect can be enhanced by ROS inhibitor NAC. Pretreated with NAC can enhance the cell cycle block but not apoptosis induced by RA. Moreover, as a by-production of RA, ROS induced autophagy can attenuate RA's antitumor activity, and autophagy inhibitor 3-MA could recover RA's antitumor effect. These results demonstrated that ROS and autophagy could be considered as two pro-tumor factors in some conditions. The combination of RA and ROS inhibitor or autophagy inhibitor or both of them may be the novel strategies at least in ovarian cancer therapy.