Response of a mouse fibrosarcoma to withaferin A and radiation

The in-vivo growth response of a transplantable mouse fibrosarcoma to withaferin A, a plant steroidal lactone, with or without local gamma radiation, was studied. Solid tumours were obtained by injecting 5 x 10⁵ tumour cells on the dorsal skin of adult Swiss albino mice. Tumours of 100 ± 10 mm³ were treated with 10-60 mg kg^-1 withaferin A with or without local exposure to 30 Gy gamma radiation. In another experiment tumour bearing mice were given 40 or 60 mg kg^-1 withaferin A intraperitoneally, orally or intramuscularly to study the influence of route of administration. Tumour response was assessed by the tumour volume doubling time (VDT), growth delay (GD), complete response (complete regression with no regrowth at the primary site) and partial response (≥ 50% regression from the treated volume) over 120 days. Withaferin A (10-60 mg kg^-1) produced a dose-dependent linear increase in VDT and GD. This increase was significant up to a dose of 40 mg kg^-1. At 40 mg kg^-1, the intraperitoneal route gave the maximum tumour response. The effectiveness of the oral route could be increased by increasing the dose. Radiation alone produced a 33% complete and 33% partial response and enhanced VDT significantly compared with control. Injection of 10-40 mg kg^-1 withaferin A followed by radiation produced a further drug dose-dependent increase in VDT, GD and total response. The results indicate that withaferin A could be useful in the radiotherapy of solid tumours and a dose of 40 mg kg^-1 appears to be optimum for single administration.