Eicosapentaenoic acid: The role in malignant diseases

Abstract

A number of epidemiological and experimental evidences have linked polyunsaturated fatty acids (PUFA) of n-3 series to reduced cancer risk. Particularly the long chain n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to have potent antitumor effects. Increased consumption of EPA and DHA, found naturally in sea food, may lower the risk of cancer development. Both EPA and DHA also exert antiangiogenic effects, inhibiting production of many important angiogenic mediators. Furthermore, nutritional intervention with EPA decreases weight loss, promotes weight gain and increases survival times in patients affected with cancer cachexia. Nature of antitumor effects of EPA is not clearly understood, but one of the mechanisms is competitive inhibition of the use of arachidonic acid, an n-6 fatty acid, for the production of eicosanoids. Eicosanoids derived from arachidonic acid have been associated with both tumor promotion and progression. EPA is also a potent angiogenesis inhibitor, which suppresses production of crucial angiogenic mediators namely: Vascular Endothelial Growth Factor (VEGF), Platelet-Derived Growth Factor (PDGF), cyclo-oxygenase 2 (COX-2), Nuclear Factor Kappa Beta (NFKB) and nitric oxide. Proportion of EPA in plasma or erythrocyte phospholipids in healthy individuals depends on the dietary intake and endogenous metabolism. However, clinical evidence suggests that EPA status in newly diagnosed cancer patients and patients undergoing chemotherapy is usually markedly lower in comparison with healthy population. Low EPA status was found in patients with cancer on different sites, including pancreatic, lung, prostate cancer, and non-Hodgkin lymphoma. In addition, EPA and the other n-3 PUFA were shown to be particularly depleted in advanced cancer patients, during chemotherapy and in cancer patients close to death. Therefore, both the disease itself and therapeutic treatments may be contributing factors in the decline of EPA status in patients with cancer. The present review will focus on the current knowledge related to the anticancer effects of EPA on different stages of disease, from initiation and promotion, to progression and neoplastic transformation.