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Uma Devi P, Kamath R.
J Radiat Res (Tokyo). 2003 Mar;44(1):1-6
Radiosensitizing effect of
withaferin A combined with hyperthermia on mouse fibrosarcoma and melanoma.
Department of Research, Jawaharlal Nehru Cancer Hospital and Research Centre,
Idgah Hills, Post Box no.32, Bhopal 462 001, India.
jncancer@sancharnet.in
The effect of withaferin A, a plant withanolide, alone or in combination with
acute and fractionated radiotherapy and/or hyperthermia, was tested on two mouse
tumors, B16F1 melanoma and fibrosarcoma, grown in C57BL and Swiss albino mice,
respectively. Tumors were exposed locally to 30 or 50 Gy gamma radiation as
acute dose, or 5 fractions of 10 Gy. Withaferin A, 40 mg/kg, was injected
intraperitoneally, 1h before acute irradiation, or 30 mg/kg before every 10 Gy
fraction. Local hyperthermia, 43 degrees C for 30 min, followed acute RT or
first fraction of 10 Gy. Withaferin A, radiation and hyperthermia, individually
and in bimodality treatments, produced no complete response (CR) in melanoma.
Some CR were seen in fibrosarcoma, which increased after bimodality treatments.
Trimodality treatment synergistically increased CR to 37% in melanoma and to 64%
in fibrosarcoma. Fractionated radiotherapy (10 Gy x 5) was more effective (25%
CR) than acute dose of 50 Gy (0% CR) on melanoma, while there was no difference
between the response of fibrosarcoma to the two regimens. Withaferin A with
fractionated radiotherapy synergistically increased the CR of both tumors;
hyperthermia further enhanced this effect. Utility of withaferin A in increasing
the clinical response of radioresistant tumors to fractionated radiotherapy has
to be explored.
PMID: 12841592
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