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

Abstract

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 muM. One-hour treatment with a nontoxic dose of 2. 1 muM 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 4 h after treatment with 10. 5 muM withaferin A for 1 h. The applicability of this drug as a radiosensitizer in cancer therapy needs to be explored.