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ω-3 Long Chain Polyunsaturated Fatty Acids as Sensitizing Agents and Multidrug Resistance Revertants in Cancer Therapy

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via D. Trentacoste 2, Milano 20134, Italy
Department of Oncology, Università degli Studi di Torino, Via Santena 5/bis, Torino 10126, Italy
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2017, 18(12), 2770;
Received: 4 October 2017 / Revised: 23 November 2017 / Accepted: 16 December 2017 / Published: 20 December 2017
(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease: New Knowledge)
Chemotherapy efficacy is strictly limited by the resistance of cancer cells. The ω-3 long chain polyunsaturated fatty acids (ω-3 LCPUFAs) are considered chemosensitizing agents and revertants of multidrug resistance by pleiotropic, but not still well elucidated, mechanisms. Nowadays, it is accepted that alteration in gene expression, modulation of cellular proliferation and differentiation, induction of apoptosis, generation of reactive oxygen species, and lipid peroxidation are involved in ω-3 LCPUFA chemosensitizing effects. A crucial mechanism in the control of cell drug uptake and efflux is related to ω-3 LCPUFA influence on membrane lipid composition. The incorporation of docosahexaenoic acid in the lipid rafts produces significant changes in their physical-chemical properties affecting content and functions of transmembrane proteins, such as growth factors, receptors and ATP-binding cassette transporters. Of note, ω-3 LCPUFAs often alter the lipid compositions more in chemoresistant cells than in chemosensitive cells, suggesting a potential adjuvant role in the treatment of drug resistant cancers. View Full-Text
Keywords: ω-3; PUFA; chemoresistance; membrane; DHA; EPA ω-3; PUFA; chemoresistance; membrane; DHA; EPA
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Corsetto, P.A.; Colombo, I.; Kopecka, J.; Rizzo, A.M.; Riganti, C. ω-3 Long Chain Polyunsaturated Fatty Acids as Sensitizing Agents and Multidrug Resistance Revertants in Cancer Therapy. Int. J. Mol. Sci. 2017, 18, 2770.

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