Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo
A C Sharada1, F E Solomon, P U Devi
1Department of Radiobiology, Kasturba Medical College, Manipal, Karnataka, India.
Abstract:
The antitumor and radiosensitizing effects of withaferin A (WA), a steroidal lactone from Withania somnifera, was studied on Ehrlich ascites carcinoma in vivo. The acute LD50(14) for WA in Swiss mice was approximately 80 mg/kg. Twenty-four hours after i.p. inoculation of 10(6) tumor cells, WA was injected i.p. at different dose fractions (5 or 7.5 mg/kg x 8, 10 mg/kg x 5, 20 or 30 mg/kg x 2) with or without abdominal gamma irradiation (RT, 75. Gy) after the first drug dose. Increase in life span and tumor-free survival were studied up to 120 days. The drug inhibited tumor growth and increased survival, which was dependent on the WA dose per fraction rather than the total dose. Combination of RT with all the drug schedules increased tumor cure and tumor-free survival, the best effect seen after 2 fractions of 30 mg/kg each. In another 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 inoculation 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.
Insights
Withaferin A (WA) demonstrated antitumor effects against Ehrlich ascites carcinoma in mice. Combining WA with radiation therapy significantly enhanced tumor cure rates and survival, particularly with fractionated dosing.
Area of Science:
- Pharmacology
- Cancer Research
- Natural Products
Background:
- Withaferin A (WA), a steroidal lactone from Withania somnifera, is being investigated for its therapeutic potential.
- Ehrlich ascites carcinoma serves as a model for studying antitumor agents.
Purpose of the Study:
- To evaluate the antitumor and radiosensitizing effects of Withaferin A (WA) on Ehrlich ascites carcinoma in vivo.
- To determine optimal dosing and scheduling of WA, alone and in combination with gamma irradiation (RT).
Main Methods:
- Swiss mice were inoculated with Ehrlich ascites carcinoma cells.
- Withaferin A (WA) was administered intraperitoneally at various dose fractions, with or without concurrent gamma irradiation (RT).
- Survival rates and tumor-free survival were monitored up to 120 days.
Main Results:
- Withaferin A (WA) inhibited tumor growth and increased survival, with efficacy dependent on dose per fraction.
- Combination therapy of WA and RT significantly improved tumor cure and tumor-free survival compared to WA alone.
- The optimal therapeutic effect was observed with two fractions of 30 mg/kg WA combined with RT.
Conclusions:
- Withaferin A (WA) exhibits significant antitumor and radiosensitizing properties.
- Fractionated administration of WA, especially in combination with RT, offers a promising strategy for cancer treatment.
- Further research into WA-based combination therapies is warranted.
