title: Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.
abstract: Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy.
authors.affiliation: Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy. donatella.deliseo@uniroma1.it.|Department of Ecological and Biological Sciences (DEB), La Tuscia University, Largo dell'Università, 01100 Viterbo, Italy. donatella.deliseo@uniroma1.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: D'Eliseo
authors.affiliation: Department of Ecological and Biological Sciences (DEB), La Tuscia University, Largo dell'Università, 01100 Viterbo, Italy. velotti@unitus.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Velotti
keywords: apoptosis; cancer stem cells; cancer therapy; combinational therapy; cytotoxicity; docosahexaenoic acid (DHA); drug resistance; eicosapentaenoic acid (EPA); fatty acids (FAs); n-3 polyunsaturated fatty acids (PUFAs)
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