Anticancer Actions of Omega-3 Fatty Acids - Current State and Future Perspectives
Martina Wendel and Axel R. Heller
Affiliation: Department of Physiology, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Fiedlerstr. 42, D-01307 Dresden, Germany.
Omega-3 fatty acids (ω3-FA) were shown to attenuate growth and induce apoptosis in a variety of human cancer cell lines derived from colonic, pancreatic, prostate, and breast cancer. In addition, recent findings indicate that ω3-FA act synergistically with chemotherapeutic agents and may also be used to enhance tumour radiosensitivity. The mechanisms underlying the anti-tumour effects of ω3-FA are complex. Incorporation of ω3-FA in biological membranes alters the profile of lipid mediators generated during inflammatory reactions. Furthermore, ω3-FA act as ligands of nuclear peroxisome proliferator- activated receptors that attenuate transcription of NF-κB-dependent genes. Thereby, the cyclooxygenase-2/prostaglandin E2- dependent production of pro-angiogenic vascular endothelial growth factor and levels of anti-apoptotic bcl-2 and bcl-XL are decreased. Eicosanoid-independent pro-apoptotic pathways include enhanced lipid peroxidation, modulation of mitochondrial calcium homeostasis and enhanced production of reactive oxygen species as well as activation of p53. This review article will give a comprehensive overview over the pleiotropic actions of ω3-FA and will discuss the potential of ω3-FA and derivatives like conjugated eicosapentaenoic acid as important nutritional adjuvant therapeutics in the management of various human cancer diseases and the impact of nutritional ω-3 FA on cancer prevention.
Keywords: Cancer, omega-3 fatty acids, docosahexaenoic acid, eicosapentaenoic acid, cyclooxygenase, eicosanoids, lipid peroxidation, apoptosis
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