Anticancer actions of omega-3 fatty acids--current state and future perspectives.
Omega-3 fatty acids (omega3-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 omega3-FA act synergistically with chemotherapeutic agents and may also be used to enhance tumour radiosensitivity. The mechanisms underlying the anti-tumour effects of omega3-FA are complex. Incorporation of omega3-FA in biological membranes alters the profile of lipid mediators generated during inflammatory reactions. Furthermore, omega3-FA act as ligands of nuclear peroxisome proliferator-activated receptors that attenuate transcription of NF-kappaB-dependent genes. Thereby, the cyclooxygenase-2/prostaglandin E(2)-dependent production of pro-angiogenic vascular endothelial growth factor and levels of anti-apoptotic bcl-2 and bcl-X(L) 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 omega3-FA and will discuss the potential of omega3-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 omega-3 FA on cancer prevention.
Wendel
Martina
M
Department of Physiology, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany. MartinaWendel@gmx.de
Heller
Axel R
AR
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000502:physiology; D004041:Dietary Fats / Q000627:therapeutic use; D015232:Dinoprostone / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D044045:Lipoxins / Q000096:biosynthesis / Q000502:physiology; D008297:Male; D009369:Neoplasms / Q000517:prevention & control; D047492:Peroxisome Proliferator-Activated Receptors / Q000187:drug effects / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D000970:Antineoplastic Agents; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D044045:Lipoxins; D047492:Peroxisome Proliferator-Activated Receptors; D016159:Tumor Suppressor Protein p53; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D051546:Cyclooxygenase 2; D015232:Dinoprostone