In vivo growth inhibitory and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma

Adult Swiss albino mice were inoculated intraperitoneally (i.p) with 10⁶ Ehrlich ascites carcinoma cells. Twenty-four hours later they were given an i.p. injection of 10-60 mg/kg of withaferin A (WA), isolated from the roots of Withania somnifera. The tumor growth and tumor free animal survival were studied for up to 120 days. In another experiment 30 mg/kg WA was injected i.p. to mice at 1, 3 or 5 days after tumor cell injection with or without acute abdominal exposure to 7.5 Gy gamma radiation and the tumor growth and 120-day survival were studied. WA inhibited tumor growth and increased tumor free survival in a dose-dependent manner. The drug ED₅₀ for 120-day survival was ~30 mg/kg body wt. Drug treatment before irradiation synergistically increased 120-day survival even in advanced tumors. A dose of 30 mg/kg seems to be optimum for combination with radiation.