Cellular Basis of Adjuvant Role of n-3 Polyunsaturated Fatty Acids in Cancer Therapy: Molecular Insights and Therapeutic Potential against Human Melanoma

Human melanoma is a highly aggressive malignant tumor originating from epidermal melanocytes, characterized by intrinsic resistance to apoptosis and the reprogramming of proliferation and survival pathways during progression, leading to high morbidity and mortality rates. This malignancy displays a marked propensity for metastasis and often exhibits poor responsiveness to conventional therapies. Fatty acids, such as n-3 polyunsaturated fatty acids (PUFAs) docosahexaenoic and eicosapentaenoic acids, exert various physiological effects on melanoma, with increasing evidence highlighting the anti-tumorigenic, anti-inflammatory, and immunomodulatory properties. Additionally, n-3 PUFAs have demonstrated their ability to inhibit cancer metastatic dissemination. In the context of cancer treatment, n-3 PUFAs have been investigated in conjunction with chemotherapy as a potential strategy to mitigate severe chemotherapy-induced side effects, enhance treatment efficacy and improve safety profiles, while also enhancing the responsiveness of cancer cells to chemotherapy. Furthermore, dietary intake of n-3 PUFAs has been associated with numerous health benefits, including a decreased risk and improved prognosis in conditions such as heart disease, autoimmune disorders, depression and mood disorders, among others. However, the specific mechanisms underlying their anti-melanoma effects and outcomes remain controversial, particularly when comparing findings from in vivo or in vitro experimental studies to those from human trials. Thus, the objective of this review is to present data supporting the potential role of n-3 PUFA supplementation as a novel complementary approach in the treatment of malignant cancers such as melanoma.