Dioscin induces ferroptosis and synergistic cytotoxicity with chemotherapeutics in melanoma cells.

In this study, we evaluated the anti-tumor effects of dioscin, a steroidal saponin, on melanoma cells. Dioscin significantly inhibited cell viability and induced cell death of melanoma cells in a time- and dose- dependent manner. Furthermore, dioscin increased the concentration of intracellular ferrous irons, MDA and ROS. This effect could be inhibited by L-g-glutamyl-p-nitroanilide (GPNA), compound 968 and ferroptosis inhibitor ferrostatin-1 (Fer-1). Furthermore, dioscin induced ferroptosis by affecting the expression of transferrin and ferroportin which are regulators of intracellular levels of iron. Finally, dioscin in combination with various chemotherapeutic agents showed synergistic effects against melanoma cells. Our data suggested that dioscin exerted anti-tumor effects in melanoma cells by inducing ferroptosis. Dioscin alone or with other agents might be applied as a promising strategy to treat melanoma.