title: Three percent dietary fish oil concentrate increased efficacy of doxorubicin against MDA-MB 231 breast cancer xenografts.
abstract: Omega 3 polyunsaturated fatty acids (the type of fat found in fish oil) have been used to kill or slow the growth of cancer cells in culture and in animal models and to increase the effectiveness of cancer chemotherapeutic drugs. An AIN-76 diet containing 5% corn oil (CO) was modified to contain 3% w/w fish oil concentrate (FOC) and 2% CO to test whether a clinically applicable amount of FOC is beneficial during doxorubicin (DOX) treatment of cancer xenografts in mice. Compared with the diet containing 5% CO, consumption of FOC increased omega 3 polyunsaturated fatty acids and lipid peroxidation in tumor and liver, significantly decreased the ratio of glutathione peroxidase activity to superoxide dismutase activity (a putative indicator of increased oxidative stress) in tumor but not in the liver, and significantly decreased the tumor-growth rate. The decreased glutathione peroxidase:superoxide dismutase ratio, indicating an altered redox state, in the tumor of FOC-fed mice was significantly correlated with decreased tumor-growth rate. Assay of the body weight change, blood cell counts, and number of micronuclei in peripheral erythrocytes indicated that the toxicity of DOX to the host mouse was not increased in mice fed FOC. Thus, a small amount of FOC increased the effectiveness of DOX but did not increase the toxicity of DOX to the host mouse. These positive results justify clinical testing of FOC in conjunction with cancer chemotherapy.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. hardman@uthscsa.edu
authors.forename: W E
authors.initials: WE
authors.lastname: Hardman
authors.forename: C P
authors.initials: CP
authors.lastname: Avula
authors.forename: G
authors.initials: G
authors.lastname: Fernandes
authors.forename: I L
authors.initials: IL
authors.lastname: Cameron
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D001943:Breast Neoplasms / Q000473:pathology / Q000517:prevention & control*; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004032:Diet; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018384:Oxidative Stress / Q000187:drug effects; D012044:Regression Analysis; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase