The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy

Dietary intake of long-chain ω-3 (or n-3) polyunsaturated fatty acids (PUFA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) can affect numerous processes in the body, including cardiovascular, neurological and immune functions, as well as cancer. Studies on human cancer cell lines, animal models and preliminary trials with human subjects suggest that administration of EPA and DHA, found naturally in our diet in fatty fish, can alter toxicities and/or activity of many drugs used to treat cancer. Multiple mechanisms are proposed to explain how n-3 PUFA modulate the tumor cell response to chemotherapeutic drugs. n-3 PUFA are readily incorporated into cell membranes and lipid rafts, and their incorporation may affect membrane-associated signaling proteins such as Ras, Akt and Her-2/neu. Due to their high susceptibility to oxidation, it has also been proposed that n-3 PUFA may cause irreversible tumor cell damage through increased lipid peroxidation. n-3 PUFA may increase tumor cell susceptibility to apoptosis by altering expression or function of apoptotic proteins, or by modulating activity of survival-related transcription factors such as nuclear factor-κB. Some studies suggest n-3 PUFA may increase drug uptake or even enhance drug activation (e.g., in the case of some nucleoside analogue drugs). Further research is warranted to identify specific mechanisms by which n-3 PUFA increase chemotherapy efficacy and to determine the optimal cellular/membrane levels of n-3 PUFA required to promote these mechanisms, such that these fatty acids may be prescribed as adjuvants to chemotherapy.