Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects.
The cancer chemotherapeutic efficacy of the topoisomerase I inhibitor, CPT-11 (irinotecan) is often limited by the induction of severe delayed diarrhoea. In animal studies, CPT-11 use is associated with histopathological damage to the mucosa of the small and large intestines. Results from the present study demonstrate that 60 mg CPT-11 per kg body weight (i.v. q4d x 6) halted the growth, but did not cause significant regression, of MCF7 human breast carcinoma xenografts in mice fed a diet containing 7% corn oil. However, when the diet of the MCF7-bearing mice was supplemented with 3% or 6% fish oil, the same CPT-11 treatment caused significant regression of the MCF7 xenograft. Histomorphometric analyses of intestinal mucosa of mice treated with CPT-11 and fed the diet containing 7% com oil indicated that treatment with CPT-11 induced structural changes in the intestinal mucosa which persisted at least 5 days after the last dose of CPT-11. The intestinal mucosal architecture of mice that were treated with CPT-11 and fed the diets containing fish oil was largely unchanged from the architecture of the group of mice which did not receive CPT-11. These findings indicate that fish oil supplements may be a useful adjunct to CPT-11 treatment.
Hardman
W E
WE
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 78284, USA.
Moyer
M P
MP
Cameron
I L
IL
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D003106:Colon / Q000187:drug effects / Q000473:pathology; D003314:Corn Oil / Q000008:administration & dosage / Q000494:pharmacology; D004357:Drug Synergism; D004386:Duodenum / Q000187:drug effects / Q000473:pathology; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000517:prevention & control*; D006801:Humans; D000077146:Irinotecan; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005395:Fish Oils; D017392:Thiobarbituric Acid Reactive Substances; D000077146:Irinotecan; D003314:Corn Oil; D002166:Camptothecin