Antitumor and radiosensitizing effects of withaferin A on mouse Ehrlich ascites carcinoma in vivo.
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.
Sharada
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AC
Department of Radiobiology, Kasturba Medical College, Manipal, Karnataka, India.
Solomon
F E
FE
Devi
P U
PU
Udupa
N
N
Srinivasan
K K
KK
D000008:Abdominal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000532:radiotherapy; D003037:Cobalt Radioisotopes / Q000627:therapeutic use; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008136:Longevity; D008297:Male; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011867:Radioisotope Teletherapy; D011879:Radiotherapy Dosage; D012074:Remission Induction; D015996:Survival Rate; D054358:Withanolides
D000972:Antineoplastic Agents, Phytogenic; D003037:Cobalt Radioisotopes; D011838:Radiation-Sensitizing Agents; D054358:Withanolides; C009684:withaferin A; D004875:Ergosterol