Essential fatty acids enhance free radical generation and lipid peroxidation toinduce apoptosis of tumor cells

Abstract

Selective elimination of tumor cells with little or no effects on normal cells is desirablefor the treatment of cancer. Tumor cells are deficient in polyunsaturated fatty acids ([PUFAs]especially g.linolenic, arachidonic, eicosapentaneoic and docosahexaenoic acids) caused by decreased activity of enzymes d.6 and d.5 desaturases. Exposure of tumor cells to adequate amounts of these fatty acids induces apoptosis in these tumor cells by augmenting free radicalgeneration and lipid peroxidation, while normal cells remain unaffected. Studies have revealedthat even tumor cell drug resistance can be overcome by enhancing the incorporation of PUFAs in the membranes of tumor cells. Therefore, it is suggested that methods designed to selectively deliver PUFAs to tumor cells could be a novel method of inducing apoptosis in tumor cells. Such selective delivery of PUFAs to tumor cells can be achieved by intratumoral injection, intra-arterial administration into tumor-feeding vessels, conjugation of PUFAs to growth factors and/or monoclonal antibodies to growth factors and cytokines (e.g., TNF.a) and/or complexing PUFAs with conventional anticancer drugs and infusing them parenterally.