Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional\ncytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of\ndrug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids\n(PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic\nactivity by inducing apoptotic cell death in human cancer cells either alone or in combination\nwith conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells\nto conventional therapies, possibly improving their efficacy especially against cancers resistant\nto treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective\ncytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on\nstudies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing\nthe molecular mechanisms underlying this effective and selective activity. Here, we highlight the\nmultiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis\ncan allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against\ncancer, providing specific information and support to design future pre-clinical and clinical studies\nfor a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy
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