Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin

Purpose: The anticancer activity of Ohm -3 poly unsaturated fatty acids (Oh m -3 PUFA) has been shown in a large number of studies. This study was unde rtaken to analyze the combined effect of Ohm -3 PUFA and antioxidative vita mins on the level of spontaneous metastatic dissemination. The supportive e ffect of this dietary combination on chemotherapy with cisplatin (CP) was d etermined in parallel. Methods: C57BL/6J mice bearing the Lewis lung carcin oma 3LL were fed ad libitum one of three isocaloric diets containing 5% soy bean 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 a nd lung histology were followed. Results: Both the FO dietary groups showed significantly lower tumor development than the SO group in all examined pa rameters, indicating that Ohm -3 PUFA have anticancer activity. However, th e FO diet, in comparison with the FO+E+C diet induced a significantly slowe r rate of tumor growth, and lower metastatic load, as reflected in lung wei ght. The decrease in the anticancer activity of FO by the addition of vitam ins E and C suggests that in situ oxidation of Ohm -3 PUFA underlies their anticancer action. It is thus proposed that oxidized Ohm -3 PUFA accumulate s in the membranes and the cytosol of tumor cells, reducing their vitality and eventually leading to their death. No signs of anorexia or cachexia wer e observed in either FO group, in contrast to the SO group. CP treatment wi th 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 vitami ns E and C after resection of the primary growth. This regimen could be tra nslated to a combined therapy for human cancer. Conclusions: Diets enriched with Ohm -3 PUFA may have beneficial anticancer effects in particular when containing only basal amounts of antioxidants such as vitamin E or C. Furt hermore, the addition of drugs which promote oxidation of Ohm -3 PUFA, such as ferrous salts (e.g. as prescribed for the treatment of anemia), may fur ther increase these effects. However, the supportive effect of Ohm -3 PUFA in chemotherapy (e.g. with CP) increases when vitamins E and C are also inc luded.