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. LD50 for survival was 16 microM. One-hour treatment with a non-toxic dose of 2.1 microM 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 G2/M block, with a maximum accumulation of cells in G2-M phase at 4 h after treatment with 10.5 microM withaferin A in 1 h. The applicability of this drug as a radiosensitizer in cancer therapy needs to be explored.
Devi
P U
PU
Department of Radiobiology, Kasturba Medical College, Manipal, India.
Akagi
K
K
Ostapenko
V
V
Tanaka
Y
Y
Sugahara
T
T
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005720:Gamma Rays; D010946:Plants, Medicinal / Q000737:chemistry*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D054358:Withanolides
D011838:Radiation-Sensitizing Agents; D054358:Withanolides; C009684:withaferin A; D004875:Ergosterol