期刊
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
卷 9, 期 4, 页码 457-470出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1871520610909040457
关键词
Cancer; omega-3 fatty acids; docosahexaenoic acid; eicosapentaenoic acid; cyclooxygenase; eicosanoids; lipid peroxidation; apoptosis
Omega-3 fatty acids (omega 3-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 omega 3-FA act synergistically with chemotherapeutic agents and may also be used to enhance tumour radiosensitivity. The mechanisms underlying the anti-tumour effects of omega 3-FA are complex. Incorporation of omega 3-FA in biological membranes alters the profile of lipid mediators generated during inflammatory reactions. Furthermore, omega 3-FA act as ligands of nuclear peroxisome proliferator-activated receptors that attenuate transcription of NF-kappa B-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 omega 3-FA and will discuss the potential of omega 3-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.
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