Withaferin A: A new radiosensitizer from the Indian medicinal plant Withania somnifera

Withaferin A, a steroidal lactone isolated from the roots of the Indian medicinal plant Withania somnifera, reduced survival of V79 cells in a dose-dependent manner. LD(50) for survival was 16 mu M. One-hour treatment with a non-toxic dose of 2.1 mu M before irradiation significantly enhanced cell killing, giving a sensitizer enhancement ratio (SER) of 1.5 for 37% survival and 1.4 for 10% survival. SER increased with drug dose, but at higher doses the increased lethality appears to be due to two effects-drug toxicity and radiosensitization. The drug induced a G(2)/M block, with a maximum accumulation of cells in G(2)-M phase at h after treatment with 10.5 mu M withaferin A for 1 h. The applicability of this drug as a radiosensitizer in cancer therapy needs to be explored.