Document Detail

Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin.
MedLine Citation:
PMID:  11221959     Owner:  NLM     Status:  MEDLINE    
PURPOSE: The anticancer activity of omega-3 polyunsaturated fatty acids (omega-3 PUFA) has been shown in a large number of studies. This study was undertaken to analyze the combined effect of omega-3 PUFA and antioxidative vitamins on the level of spontaneous metastatic dissemination. The supportive effect of this dietary combination on chemotherapy with cisplatin (CP) was determined in parallel. METHODS: C57BL/6J mice bearing the Lewis lung carcinoma 3LL were fed ad libitum one of three isocaloric diets containing 5% soybean oil supplemented with 40 mg/kg alpha-tocopherol acetate (SO diet), or 4% fish oil plus 1% corn oil, and basal amounts of vitamin E (FO diet) or FO diet supplemented with vitamins E and C (FO+E+C diet). These diets were tested in combination with the conventional cytotoxic agent CP in a series of regimens. Tumor growth, feed consumption, body weight, lung metastasis and lung histology were followed. RESULTS: Both the FO dietary groups showed significantly lower tumor development than the SO group in all examined parameters, indicating that omega-3 PUFA have anticancer activity. However, the FO diet, in comparison with the FO+E+C diet induced a significantly slower rate of tumor growth, and lower metastatic load, as reflected in lung weight. The decrease in the anticancer activity of FO by the addition of vitamins E and C suggests that in situ oxidation of omega-3 PUFA underlies their anticancer action. It is thus proposed that oxidized omega-3 PUFA accumulates in the membranes and the cytosol of tumor cells, reducing their vitality and eventually leading to their death. No signs of anorexia or cachexia were observed in either FO group, in contrast to the SO group. CP treatment with the SO diet had no apparent therapeutic effect, while with the FO diets it reduced the metastatic load. The best regimen of this combined treatment was FO diet followed by CP treatment with FO diet supplemented with vitamins E and C after resection of the primary growth. This regimen could be translated to a combined therapy for human cancer. CONCLUSIONS: Diets enriched with omega-3 PUFA may have beneficial anticancer effects in particular when containing only basal amounts of antioxidants such as vitamin E or C. Furthermore, the addition of drugs which promote oxidation of omega-3 PUFA, such as ferrous salts (e.g. as prescribed for the treatment of anemia), may further increase these effects. However, the supportive effect of omega-3 PUFA in chemotherapy (e.g. with CP) increases when vitamins E and C are also included.
D Yam; A Peled; M Shinitzky
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  47     ISSN:  0344-5704     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2001  
Date Detail:
Created Date:  2001-02-26     Completed Date:  2001-03-01     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  34-40     Citation Subset:  IM    
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
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MeSH Terms
Analysis of Variance
Antineoplastic Agents / therapeutic use*
Ascorbic Acid / therapeutic use*
Carcinoma, Lewis Lung / secondary,  therapy*
Cisplatin / therapeutic use*
Combined Modality Therapy / methods
Drug Screening Assays, Antitumor
Fatty Acids, Omega-3 / therapeutic use*
Mice, Inbred C57BL
Soybean Oil / therapeutic use
Vitamin E / therapeutic use*
Reg. No./Substance:
0/Antineoplastic Agents; 0/Fatty Acids, Omega-3; 1406-18-4/Vitamin E; 15663-27-1/Cisplatin; 50-81-7/Ascorbic Acid; 8001-22-7/Soybean Oil

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