ANTITUMOR AND RADIOSENSITIZING EFFECTS OF WITHAFERIN A ON MOUSE EHRLICH ASCITES-CARCINOMA IN-VIVO

The antitumor and radiosensitizing effects of withaferin A (WA), a ste roidal lactone from Withania somnifera, was studied on Ehrlich ascites carcinoma in vivo, The acute LD(50(14)) for WA in Swiss mice was simi lar to 80 mg/kg. Twenty-four hours after i.p. inoculation of 10(6) tum or cells, WA was injected i.p. at different dose fractions (5 or 7.5 m g/kg x 8, 10 mg/kg x 5, 20 or 30 mg/kg x 2) with or without abdominal gamma irradiation (RT, 7.5 Gy) after the first drug dose, Increase in life span and tumor-free survival were studied up to 120 days. The dru g inhibited tumor growth and increased survival, which was dependent o n the WA dose per fraction rather than the total dose. Combination of RT with all the drug schedules increased tumor cure and tumor-free sur vival, the best effect seen after 2 fractions of 30 mg/kg each, In ano ther experiment WA was given as 2 (40 mg/kg x 2), 3 (30 mg/kg x 3) or 4 (20 mg/kg x 4) fractions at 5, 7 or 10 days after tumor inoculation with or without RT after the first drug dose, At 7 and 10 days after i noculation the drug was effective only at 40 mg/kg x 2, but with RT 30 mg/kg x 3 produced an equal effect (20% survival) on 7 day old tumors .