{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T11:39:25Z","timestamp":1792237165337,"version":"4.4.0"},"reference-count":167,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2016,1,26]],"date-time":"2016-01-26T00:00:00Z","timestamp":1453766400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Cancer is a major disease worldwide. Despite progress in cancer therapy, conventional cytotoxic therapies lead to unsatisfactory long-term survival, mainly related to development of drug resistance by tumor cells and toxicity towards normal cells. n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), can exert anti-neoplastic activity by inducing apoptotic cell death in human cancer cells either alone or in combination with conventional therapies. Indeed, n-3 PUFAs potentially increase the sensitivity of tumor cells to conventional therapies, possibly improving their efficacy especially against cancers resistant to treatment. Moreover, in contrast to traditional therapies, n-3 PUFAs appear to cause selective cytotoxicity towards cancer cells with little or no toxicity on normal cells. This review focuses on studies investigating the cytotoxic activity of n-3 PUFAs against cancer cells via apoptosis, analyzing the molecular mechanisms underlying this effective and selective activity. Here, we highlight the multiple molecules potentially targeted by n-3 PUFAs to trigger cancer cell apoptosis. This analysis can allow a better comprehension of the potential cytotoxic therapeutic role of n-3 PUFAs against cancer, providing specific information and support to design future pre-clinical and clinical studies for a better use of n-3 PUFAs in cancer therapy, mainly combinational therapy.<\/jats:p>","DOI":"10.3390\/jcm5020015","type":"journal-article","created":{"date-parts":[[2016,1,26]],"date-time":"2016-01-26T10:00:42Z","timestamp":1453802442000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":259,"title":["Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy"],"prefix":"10.3390","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2358-8236","authenticated-orcid":false,"given":"Donatella","family":"D\u2019Eliseo","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00161 Rome, Italy"},{"name":"Department of Ecological and Biological Sciences (DEB), La Tuscia University, Largo dell\u2019Universit\u00e0, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-4340","authenticated-orcid":false,"given":"Francesca","family":"Velotti","sequence":"additional","affiliation":[{"name":"Department of Ecological and Biological Sciences (DEB), La Tuscia University, Largo dell\u2019Universit\u00e0, 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,1,26]]},"reference":[{"key":"ref_1","first-page":"85","article-title":"Global burden of cancer","volume":"79","author":"Ma","year":"2006","journal-title":"J. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/B978-0-12-397927-8.00010-5","article-title":"Resistance to chemotherapy: Short-term drug tolerance and stem cell-like subpopulations","volume":"65","author":"Basile","year":"2012","journal-title":"Adv. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/35102167","article-title":"Stem cells, cancer, and cancer stem cells","volume":"414","author":"Reya","year":"2001","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1158\/1078-0432.CCR-10-2538","article-title":"Cancer stem cells and chemosensitivity","volume":"17","author":"Vigneri","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"E170","DOI":"10.1073\/pnas.1210419110","article-title":"Defining principles of combination drug mechanisms of action","volume":"110","author":"Pritchard","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1159\/000228993","article-title":"Fats and fatty acids in human nutrition: Introduction","volume":"55","author":"Burlingame","year":"2009","journal-title":"Ann. Nutr. Metable"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.jada.2008.12.022","article-title":"A systemic review of the roles of n-3 fatty acids in health and disease","volume":"109","author":"Riediger","year":"2009","journal-title":"J. Am. Diet. Assoc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.bbalip.2014.08.010","article-title":"Marine \u03c9-3 Fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance","volume":"1851","author":"Calder","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1017\/S0007114514003742","article-title":"Fish, a Mediterranean source of n-3 PUFA: Benefits do not justify limiting consumption","volume":"113","author":"Gil","year":"2015","journal-title":"Br. J. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/MCO.0b013e32835d2d99","article-title":"\u03c9-3 Fatty acids in cancer","volume":"16","author":"Laviano","year":"2013","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"807","DOI":"10.5114\/aoms.2015.53302","article-title":"Potential role of dietary lipids in the prophylaxis of some clinical conditions","volume":"11","author":"Bhagat","year":"2015","journal-title":"Arch. Med. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.pharmthera.2015.01.008","article-title":"Anti-tumor activities of lipids and lipid analogues and their development as potential anticancer drugs","volume":"150","author":"Murray","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/S0140-6736(71)91658-8","article-title":"Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos","volume":"1","author":"Bang","year":"1971","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s40495-015-0043-9","article-title":"n-3 Polyunsaturated fatty acids and their role in cancer chemoprevention","volume":"5","author":"Gu","year":"2015","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1021\/tx200314p","article-title":"Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits and potential harmful effects","volume":"24","author":"Serini","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s11888-014-0241-6","article-title":"Mechanisms by which pleiotropic amphiphilic n-3 PUFA reduce colon cancer risk","volume":"10","author":"Chapkin","year":"2014","journal-title":"Curr. Colorectal Cancer Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1002\/ijc.29672","article-title":"JPHC Study Group. Fish, n-3 polyunsaturated fatty acids and n-6 polyunsaturated fatty acids intake and breast cancer risk: The Japan Public Health Center-based prospective study","volume":"137","author":"Kiyabu","year":"2015","journal-title":"Int. J. Cancer."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1093\/jnci\/djt174","article-title":"Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial","volume":"105","author":"Brasky","year":"2013","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/MCO.0000000000000038","article-title":"Dietary fatty acids in health and disease: Greater controversy, greater interest","volume":"17","author":"Calder","year":"2014","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"143109","DOI":"10.1155\/2015\/143109","article-title":"\u03c9-3 Polyunsaturated fatty acids: The way forward in times of mixed evidence","volume":"2015","author":"Weylandt","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.canlet.2008.03.044","article-title":"Multi-targeted therapy of cancer by \u03c9-3 Fatty acids","volume":"269","author":"Berquin","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s10495-008-0298-2","article-title":"Dietary polyunsaturated fatty acids as inducers of apoptosis: Implications for cancer","volume":"14","author":"Serini","year":"2009","journal-title":"Apoptosis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.yexcr.2010.02.039","article-title":"\u03c9-3 Fatty acids in cancer, the protectors of good and the killers of evil?","volume":"316","author":"Gleissman","year":"2010","journal-title":"Exp. Cell Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/bjc.2012.586","article-title":"Marine polyunsaturated fatty acids and cancer therapy","volume":"108","author":"Vaughan","year":"2013","journal-title":"Br. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.jnutbio.2008.02.003","article-title":"The potential for treatment with dietary long-chain polyunsaturated n-3 fatty acids during chemotherapy","volume":"19","author":"Biondo","year":"2008","journal-title":"J. Nutr. Biochem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/biof.181","article-title":"Docosahexaenoic acid: A natural powerful adjuvant that improves efficacy for anticancer treatment with no adverse effects","volume":"37","author":"Siddiqui","year":"2011","journal-title":"Biofactors"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1517\/17425247.2011.618183","article-title":"The powerful applications of polyunsaturated fatty acids in improving the therapeutic efficacy of anticancer drugs","volume":"9","author":"Wang","year":"2012","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"310186","DOI":"10.1155\/2013\/310186","article-title":"Dietary \u03c9 -3 polyunsaturated fatty acid DHA: A potential adjuvant in the treatment of cancer","volume":"2013","author":"Merendino","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.ctrv.2012.07.001","article-title":"Selective sensitization of tumors to chemotherapy by marine-derived lipids: A review","volume":"39","author":"Hajjaji","year":"2013","journal-title":"Cancer Treat. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.clnu.2014.11.005","article-title":"\u03c9-3 Supplements for patients in chemotherapy and\/or radiotherapy: A systematic review","volume":"34","author":"Waitzberg","year":"2015","journal-title":"Clin. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0952-3278(98)90128-4","article-title":"Can tumour cell drug resistance be reversed by essential fatty acids and their metabolites?","volume":"58","author":"Das","year":"1998","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1080\/01635580903532366","article-title":"DHA alters expression of target proteins of cancer therapy in chemotherapy resistant SW620 colon cancer cells","volume":"62","author":"Slagsvold","year":"2010","journal-title":"Nutr. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1080\/07315724.2011.10719969","article-title":"Long-chain polyunsaturated fatty acids promote paclitaxel cytotoxicity via inhibition of the MDR1 gene in the human colon cancer Caco-2 cell line","volume":"30","author":"Kuan","year":"2011","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/1476-4598-12-137","article-title":"\u03c9 3 Fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition","volume":"12","author":"Gelsomino","year":"2013","journal-title":"Mol. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0006-291X(87)91281-2","article-title":"Polyunsaturated fatty acids augment free radical generation in tumor cells in vitro","volume":"145","author":"Das","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1007\/s005350050071","article-title":"Inhibitory effects of n--3 polyunsaturated fatty acids on sigmoid colon cancer transformants","volume":"33","author":"Tsai","year":"1998","journal-title":"J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.chemphyslip.2008.02.009","article-title":"Anticancer properties of oxidation products of docosahexaenoic acid","volume":"153","author":"Siddiqui","year":"2008","journal-title":"Chem. Phys. Lipids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1158\/1940-6207.CAPR-08-0197","article-title":"Regulation of colorectal cancer cell apoptosis by the n-3 polyunsaturated fatty acids Docosahexaenoic and Eicosapentaenoic","volume":"2","author":"Giros","year":"2009","journal-title":"Cancer Prev. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.jnutbio.2007.12.005","article-title":"Docosahexaenoic acid induces apoptosis in colorectal carcinoma cells by modulating the PI3 kinase and p38 MAPK pathways","volume":"20","author":"Louw","year":"2009","journal-title":"J. Nutr. Biochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1002\/ijc.25473","article-title":"\u03c9-3 Fatty acid supplementation delays the progression of neuroblastoma in vivo","volume":"128","author":"Gleissman","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1093\/carcin\/bgt257","article-title":"\u03c9-3 Polyunsaturated fatty acids selectively inhibit growth in neoplastic oral keratinocytes by differentially activating ERK1\/2","volume":"34","author":"Nikolakopoulou","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.jnutbio.2012.02.001","article-title":"Lipid raft disruption by docosahexaenoic acid induces apoptosis in transformed human mammary luminal epithelial cells harboring HER-2 overexpression","volume":"24","author":"Ravacci","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.jnutbio.2014.06.013","article-title":"\u03c9-3 Fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells","volume":"25","author":"Abdi","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"254801","DOI":"10.1155\/2012\/254801","article-title":"Fatty acids in habitual diet, plasma phospholipids, and tumour and normal colonic biopsies in young colorectal cancer patients","volume":"2012","author":"Berstad","year":"2012","journal-title":"J. Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nrc2663","article-title":"Apoptosis and cancer: The genesis of a research field","volume":"9","author":"Thomas","year":"2009","journal-title":"Nature Rev. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Logue, S.E., Gorman, A.M., Cleary, P., Keogh, N., and Samali, A. (2013). Current concepts in ER stress-induced apoptosis. J. Carcinogene Mutagene.","DOI":"10.4172\/2157-2518.S6-002"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/0952-3278(92)90204-V","article-title":"Effects of eicosapentaenoic acid, \u03b3-linolenic acid and prostaglandin E1 on three human colon carcinoma cell lines","volume":"47","author":"Mengeaud","year":"1992","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1007\/s11745-999-0480-7","article-title":"Effect of eicosapentaenoic acid on the proliferation and incidence of apoptosis in the colorectal cell line HT29","volume":"34","author":"Clarke","year":"1999","journal-title":"Lipids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1054\/plef.2000.0218","article-title":"Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells","volume":"63","author":"Chen","year":"2000","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_51","first-page":"4319","article-title":"Eicosapentaenoic acid modifies cytokine activity and inhibits cell proliferation in an oesophageal cancer cell line","volume":"33","author":"Kubota","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1749-6632.2009.04716.x","article-title":"Activator protein-1 mediates docosahexaenoic acid-induced apoptosis of human gastric cancer cells","volume":"1171","author":"Lee","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3046","DOI":"10.1158\/1535-7163.MCT-09-0551","article-title":"\u03c9-3 Polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking \u03b2-catenin and cyclooxygenase-2","volume":"8","author":"Lim","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_54","first-page":"281","article-title":"Docosahexaenoic acid (DHA) induces apoptosis in human hepatocellular carcinoma cells","volume":"6","author":"Sun","year":"2013","journal-title":"Int. J. of Clin. Exp. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.bbrc.2014.12.036","article-title":"Eicosapentaenoic acid (EPA) induced apoptosis in HepG2 cells through ROS-Ca2+-JNK mitochondrial pathways","volume":"456","author":"Zhang","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/(SICI)1096-9896(199805)185:1<61::AID-PATH49>3.0.CO;2-8","article-title":"Apoptotic death of pancreatic cancer cells induced by polyunsaturated fatty acids varies with double bond number and involves an oxidative mechanism","volume":"185","author":"Hawkins","year":"1998","journal-title":"J. Pathol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1207\/s15327914nc5202_12","article-title":"Docosahexaenoic acid induces apoptosis in the human PaCa-44 pancreatic cancer cell line by active reduced glutathione extrusion and lipid peroxidation","volume":"52","author":"Merendino","year":"2005","journal-title":"Nutr. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/jcb.24354","article-title":"EPA, an \u03c9-3 Fatty acid, induces apoptosis in human pancreatic cancer cells: Role of ROS accumulation, caspase-8 activation, and autophagy induction","volume":"114","author":"Fukui","year":"2013","journal-title":"J. Cell. Biochem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1158\/0008-5472.CAN-07-2295","article-title":"Cyclooxygenase-2-derived prostaglandin E2 activates \u03b2-catenin in human cholangiocarcinoma cells: Evidence for inhibition of these signaling pathways by \u03c9 3 polyunsaturated fatty acids","volume":"68","author":"Lim","year":"2008","journal-title":"Cancer Res."},{"key":"ref_60","first-page":"7139","article-title":"Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture","volume":"50","author":"Rose","year":"1990","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/S0955-2863(02)00230-9","article-title":"Fatty acid modulation of MCF-7 human breast cancer cell proliferation, apoptosis and differentiation","volume":"13","author":"Chamras","year":"2002","journal-title":"J. Nutr. Biochem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ygyno.2005.05.024","article-title":"The effects of \u03c9-3 fatty acids on growth regulation of epithelial ovarian cancer cell lines","volume":"99","author":"Sharma","year":"2005","journal-title":"Gynecol. Oncol."},{"key":"ref_63","first-page":"785","article-title":"A combination of docosahexaenoic acid and celecoxib prevents prostate cancer cell growth in vitro and is associated with modulation of nuclear factor-\u03baB, and steroid hormone receptors","volume":"26","author":"Narayanan","year":"2005","journal-title":"Int. J. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1593\/neo.10586","article-title":"Syndecan-1-dependent suppression of PDK1\/Akt\/bad signaling by docosahexaenoic acid induces apoptosis in prostate cancer","volume":"12","author":"Hu","year":"2010","journal-title":"Neoplasia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1007\/s00262-011-1074-7","article-title":"The n3-polyunsaturated fatty acid docosahexaenoic acid induces immunogenic cell death in human cancer cell lines via pre-apoptotic calreticulin exposure","volume":"60","author":"Molinari","year":"2011","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1002\/ijc.21555","article-title":"Neuroblastoma cell death in response to docosahexaenoic acid: Sensitization to chemotherapy and arsenic induced oxidative stress","volume":"118","author":"Lindskog","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/1476-511X-10-173","article-title":"MicroRNA profile of polyunsaturated fatty acid treated glioma cells reveal apoptosis-specific expression changes","volume":"10","author":"Kitajka","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1007\/s10495-008-0246-1","article-title":"Docosahexaenoic acid induces apoptosis in lung cancer cells by increasing MKP-1 and down-regulating p-ERK1\/2 and p-p38 expression","volume":"13","author":"Serini","year":"2008","journal-title":"Apoptosis"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3892\/mmr.2013.1829","article-title":"\u03c9-3 polyunsaturated fatty acids inhibit the proliferation of the lung adenocarcinoma cell line A549 in vitro","volume":"9","author":"Yao","year":"2014","journal-title":"Mol. Med. Rep."},{"key":"ref_70","first-page":"4139","article-title":"Cell cycle arrest and apoptosis of melanoma cells by docosahexaenoic acid: Association with decreased pRb phosphorylation","volume":"60","author":"Albino","year":"2000","journal-title":"Cancer Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1194\/jlr.M400474-JLR200","article-title":"Role of \u03c9-3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma","volume":"46","author":"Denkins","year":"2005","journal-title":"J. Lipid Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/sj.leu.2401030","article-title":"Multiplication and death-type of leukemia cell lines exposed to very long-chain polyunsaturated fatty acids","volume":"12","author":"Finstad","year":"1998","journal-title":"Leukemia"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1042\/bj3360451","article-title":"Cell proliferation, apoptosis and accumulation of lipid droplets in U937-1 cells incubated with eicosapentaenoic acid","volume":"336","author":"Finstad","year":"1998","journal-title":"Biochem. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0304-3835(99)00224-4","article-title":"Induction of apoptosis in HL-60 cells by eicosapentaenoic acid (EPA) is associated with downregulation of BCL-2 expression","volume":"145","author":"Chiu","year":"1999","journal-title":"Cancer Letters"},{"key":"ref_75","first-page":"737","article-title":"Docosahexaenoic acid modulates different genes in cell cycle and apoptosis to control growth of human leukemia HL-60 cells","volume":"25","author":"Chiu","year":"2004","journal-title":"Int J Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0167-4889(00)00128-2","article-title":"Docosahexaenoic acid induces apoptosis in Jurkat cells by a protein phosphatase-mediated process","volume":"1499","author":"Siddiqui","year":"2001","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11010-007-9487-5","article-title":"Involvement of PPAR-\u03b3 and p53 in DHA-induced apoptosis in Reh cells","volume":"304","author":"Zand","year":"2007","journal-title":"Mol. Cell. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"331","DOI":"10.4161\/cbt.8.4.7334","article-title":"Docosahexaenoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line","volume":"8","author":"Yamagami","year":"2009","journal-title":"Cancer Biol. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0952-3278(97)90572-X","article-title":"Cytotoxic action of \u03b1-linolenic and eicosapentaenoic acids on myeloma cells in vitro","volume":"56","author":"Das","year":"1997","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nature05384","article-title":"Identification and expansion of human colon-cancer-initiating cells","volume":"445","author":"Lombardi","year":"2007","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s10555-011-9316-x","article-title":"Essential fatty acids and their metabolites as modulators of stem cell biology with reference to inflammation, cancer, and metastasis","volume":"30","author":"Das","year":"2011","journal-title":"Cancer Metastasis Rev."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1016\/j.jnutbio.2012.03.023","article-title":"n-3 PUFA shave antiproliferative and apoptotic effects on human colorectal cancer stemlike cells in vitro","volume":"24","author":"Yang","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1158\/1940-6207.CAPR-14-0177","article-title":"\u03c9-3 Fatty acid is a potential preventive agent for recurrent colon cancer","volume":"7","author":"Vasudevan","year":"2014","journal-title":"Cancer Prev. Res."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"De Carlo, F., Witte, T.R., Hardman, W.E., and Claudio, P.P. (2013). \u03c9-3 Eicosapentaenoic acid decreases CD133 colon cancer stem-like cell marker expression while increasing sensitivity to chemotherapy. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069760"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Xiong, A., Yu, W., Liu, Y., Sanders, B.G., and Kline, K. (2015). Elimination of ALDH+ breast tumor initiating cells by docosahexanoic acid and\/or \u03b3 tocotrienol through SHP-1 inhibition of Stat3 signaling. Mol. Carcinog.","DOI":"10.1002\/mc.22291"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1093\/jnci\/87.8.587","article-title":"Influence of diets containing eicosapentaenoic or docosahexaenoic acid on growth and metastasis of breast cancer cells in nude mice","volume":"87","author":"Rose","year":"1995","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0955-2863(97)00089-2","article-title":"Dietary fish oil suppresses tumor growth and metastasis of Lewis lung carcinoma in mice","volume":"8","author":"Yam","year":"1997","journal-title":"J. Nutr. Biochem."},{"key":"ref_88","first-page":"1386","article-title":"Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: Mediation through cyclooxygenase-independent pathways","volume":"61","author":"Boudreau","year":"2001","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0304-3835(02)00432-9","article-title":"Influence of \u03c9-3 fatty acids on the growth of human colon carcinoma in nude mice","volume":"187","author":"Kato","year":"2002","journal-title":"Cancer Lett."},{"key":"ref_90","unstructured":"Camargo, C.Q., Mocellin, M.C., Pastore Silva, J.A., de Souza Fabre, M.E., Nunes, E.A., and de Moraes Trinidade, E.B. Fish oil supplementation during chemotherapy increases posterior time to tumor progression in colorectal cancer. Available online: http:\/\/.doi.org\/10.1080\/01635581.2016.1115097."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Bougnoux, P., Hajjaji, N., Ferrasson, M.N., Giraudeau, B., Couet, C., and le Floch, O. (2009). Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: A phase II trial. Br. J. Cancer, 1011978\u20131011985.","DOI":"10.1038\/sj.bjc.6605441"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1136\/gut.2010.233718","article-title":"\u03c9-3 Polyunsaturated fatty acids for the treatment and prevention of colorectal cancer","volume":"61","author":"Cockbain","year":"2012","journal-title":"Gut"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1002\/cncr.25933","article-title":"Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced non-small cell lung cancer","volume":"117","author":"Murphy","year":"2011","journal-title":"Cancer"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3945\/jn.110.128777","article-title":"Marine fatty acid intake is associated with breast cancer prognosis","volume":"141","author":"Patterson","year":"2011","journal-title":"J. Nutr."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1136\/gutjnl-2013-306445","article-title":"Anticolorectal cancer activity of the \u03c9-3 polyunsaturated fatty acid eicosapentaenoic acid","volume":"63","author":"Cockbain","year":"2014","journal-title":"Gut"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/j.clnu.2014.03.006","article-title":"Effects of an oral nutritional supplement containing eicosapentaenoic acid on nutritional and clinical outcomes in patients with advanced non-small cell lung cancer: Randomised trial","volume":"33","author":"Turcott","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.clnu.2013.09.017","article-title":"Cellular and plasma uptake of parenteral \u03c9-3 rich lipid emulsion fatty acids in patients with advanced pancreatic cancer","volume":"33","author":"Arshad","year":"2014","journal-title":"Clin. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1080\/01635581.2015.976315","article-title":"The consumption of \u03c9-3 polyunsaturated fatty acids improves clinical outcomes and prognosis in pancreatic cancer patients: A systematic evaluation","volume":"67","author":"Ma","year":"2015","journal-title":"Nutr. Cancer"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1007\/s10555-015-9572-2","article-title":"\u03c9-3 polyunsaturated fatty acids and cancer: Lessons learned from clinical trials","volume":"34","author":"Nabavi","year":"2015","journal-title":"Cancer Metastasis Rev."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Khankari, N.K., Bradshaw, P.T., Steck, S.E., He, K., Olshan, A.F., Shen, J., Ahn, J., Chen, Y., Ahsan, H., and Terry, M.B. (2015). Dietary intake of fish, polyunsaturated fatty acids, and survival after breast cancer: A population-based follow-up study on Long Island, New York. Cancer.","DOI":"10.1002\/cncr.29329"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Mocellin, M.C., Camargo, C.Q., Nunes, E.A., Fiates, G.M., and Trindade, E.B. (2015). A systematic review and meta-analysis of the n-3 polyunsaturated fatty acids effects on inflammatory markers in colorectal cancer. Clin. Nutr.","DOI":"10.1016\/j.clnu.2015.04.013"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s11745-002-0963-6","article-title":"Eicosapentaenoic acid promotes apoptosis in Ramos cells via activation of caspase-3 and -9","volume":"37","author":"Heimli","year":"2002","journal-title":"Lipids"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1054\/clnu.2002.0627","article-title":"The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes","volume":"22","author":"Llor","year":"2003","journal-title":"Clin. Nutr."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1207\/s15327914nc5001_10","article-title":"Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apoptosis and inhibits growth of colo 201 human colon cancer cells","volume":"50","author":"Danbara","year":"2004","journal-title":"Nutr. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s00280-004-0846-6","article-title":"Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil","volume":"55","author":"Calviello","year":"2005","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1194\/jlr.M700389-JLR200","article-title":"DHA induces ER stress and growth arrest in human colon cancer cells: Associations with cholesterol and calcium homeostasis","volume":"49","author":"Jakobsen","year":"2008","journal-title":"J. Lipid. Res."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0006-2952(01)00723-7","article-title":"Mechanism of apoptosis in HL-60 cells induced by n-3 and n-6 polyunsaturated fatty acids","volume":"62","author":"Arita","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_108","first-page":"1255","article-title":"Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells","volume":"19","author":"Narayanan","year":"2001","journal-title":"Int. J. Oncol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/nrc3983","article-title":"The dynamic control of signal transduction networks in cancer cells","volume":"15","author":"Kolch","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"11777","DOI":"10.3748\/wjg.v21.i41.11777","article-title":"Pathophysiological mechanisms of death resistance in colorectal carcinoma","volume":"21","author":"Huang","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0952-3278(97)90485-3","article-title":"Molecular mechanism of cellular uptake and intracellular translocation of fatty acids","volume":"57","author":"Glatz","year":"1997","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.bbamem.2008.10.011","article-title":"Polyunsaturated fatty acid-cholesterol interactions: Domain formation in membranes","volume":"1788","author":"Wassall","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Zhang, C., Yu, H., Ni, X., Shen, S., and Das, U.N. (2015). Growth inhibitory effect of polyunsaturated fatty acids (PUFAs) on colon cancer cells via their growth inhibitory metabolites and fatty acid composition changes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123256"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/j.bbamem.2013.12.021","article-title":"The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health","volume":"1838","author":"Ibarguren","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12013-012-9365-y","article-title":"Chemical-physical changes in cell membrane microdomains of breast cancer cells after \u03c9-3 PUFA incorporation","volume":"64","author":"Corsetto","year":"2012","journal-title":"Cell Biochem. Biophys."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1093\/jn\/137.3.548","article-title":"(n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells","volume":"137","author":"Schley","year":"2007","journal-title":"J. Nutr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/carcin\/bgq111","article-title":"Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association","volume":"31","author":"Rogers","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/1476-511X-10-73","article-title":"Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane","volume":"10","author":"Corsetto","year":"2011","journal-title":"Lipids Health Dis."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.bbalip.2013.10.006","article-title":"Down-regulation of lipid raft-associated onco-proteins via cholesterol-dependent lipid raft internalization in docosahexaenoic acid-induced apoptosis","volume":"1841","author":"Lee","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s12944-015-0090-6","article-title":"\u03b1-linolenic acid and docosahexaenoic acid, alone and combined with trastuzumab, reduce HER2-overexpressing breast cancer cell growth but differentially regulate HER2 signaling pathways","volume":"14","author":"Mason","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Cao, W., Ma, Z., Rasenick, M.M., Yeh, S., and Yu, J. (2012). n-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0052838"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1007\/s11745-012-3717-7","article-title":"Docosahexanoic acid improves chemotherapy efficacy by inducing CD95 translocation to lipid rafts in ER\u2212 breast cancer cells","volume":"47","author":"Ewaschuk","year":"2012","journal-title":"Lipids"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1093\/carcin\/bgt147","article-title":"Polyunsaturated fatty acids affect the localization and signaling of PIP3\/AKT in prostate cancer cells","volume":"34","author":"Gu","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1093\/carcin\/bgl254","article-title":"Docosahexaenoic acid induces proteasome-dependent degradation of \u03b2-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2","volume":"28","author":"Calviello","year":"2007","journal-title":"Carcinogenesis"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1159\/000334468","article-title":"\u03c9-3-Polyunsaturated fatty acids suppress pancreatic cancer cell growth in vitro and in vivo via downregulation of Wnt\/\u03b2-catenin signaling","volume":"11","author":"Song","year":"2011","journal-title":"Pancreatology"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jnutbio.2013.09.008","article-title":"Docosahexaenoic acid inhibited the Wnt\/\u03b2-catenin pathway and suppressed breast cancer cells in vitro and in vivo","volume":"25","author":"Xue","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1093\/carcin\/bgr132","article-title":"\u03c9-3 Fatty acids induce apoptosis in human breast cancer cells and mouse mammary tissue through syndecan-1 inhibition of the MEK-Erk pathway","volume":"32","author":"Sun","year":"2011","journal-title":"Carcinogenesis"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s10549-005-2415-z","article-title":"Mechanisms of \u03c9-3 fatty acid-induced growth inhibition in MDAMB-231 human breast cancer cells","volume":"92","author":"Schley","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10549-008-0227-7","article-title":"Fish oil targets PTEN to regulate NF\u03baB for downregulation of anti-apoptotic genes in breast tumor growth","volume":"118","author":"Mandal","year":"2009","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1007\/s10495-008-0260-3","article-title":"Differential induction of apoptosis and inhibition of the PI3-kinase pathway by saturated, monounsaturated and polyunsaturated fatty acids in a colon cancer cell model","volume":"13","author":"Engelbrecht","year":"2008","journal-title":"Apoptosis"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.4161\/auto.7.11.16658","article-title":"Docosahexaenoic acid induces autophagy through p53\/AMPK\/mTOR signaling and promotes apoptosis in human cancer cells harboring wild-type p53","volume":"7","author":"Jing","year":"2011","journal-title":"Autophagy"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"568671","DOI":"10.1155\/2013\/568671","article-title":"The \u03c9-3 polyunsaturated fatty acid DHA induces simultaneous apoptosis and autophagy via mitochondrial ROS-mediated Akt-mTOR signaling in prostate cancer cells expressing mutant p53","volume":"2013","author":"Shin","year":"2013","journal-title":"Biomed. Res. Int."},{"key":"ref_133","first-page":"239764","article-title":"Docosahexaenoic acid induces cell death in human non-small cell Lung cancer cells by repressing mTOR via AMPK activation and PI3K\/Akt inhibition","volume":"2015","author":"Kim","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Rescigno, T., Capasso, A., and Tecce, M.F. (2015). Effect of Docosahexaenoic acid on cell cycle pathways in Breast cell lines with different transformation degree. J. Cell. Physiol.","DOI":"10.1002\/jcp.25217"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1002\/pros.20830","article-title":"Docosahexaenoic acid enhances the efficacy of docetaxel in prostate cancer cells by modulation of apoptosis: The role of genes associated with the NF-\u03baB pathway","volume":"68","author":"Shaikh","year":"2008","journal-title":"Prostate"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1002\/pros.21359","article-title":"Docosahexaenoic acid selectively induces human prostate cancer cell sensitivity to oxidative stress through modulation of NF-\u03baB","volume":"71","author":"Cavazos","year":"2011","journal-title":"Prostate"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1186\/1471-2407-14-481","article-title":"Docosahexaenoic acid-induced apoptosis is mediated by activation of mitogen-activated protein kinases in human cancer cells","volume":"14","author":"Jeong","year":"2014","journal-title":"BMC Cancer"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1096\/fj.09-137919","article-title":"Docosahexaenoic acid metabolome in neural tumors: Identification of cytotoxic intermediates","volume":"24","author":"Gleissman","year":"2010","journal-title":"FASEB J."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1007\/s11745-004-1339-7","article-title":"Resolvins, docosatrienes, and neuroprotectins, novel \u03c9-3-derived mediators, and their endogenous aspirin-triggered epimers","volume":"39","author":"Serhan","year":"2004","journal-title":"Lipids"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jasms.2006.09.002","article-title":"Resolvin D1, protectin D1, and related docosahexaenoic acid-derived products: Analysis via electrospray\/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms","volume":"18","author":"Hong","year":"2007","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1158\/1535-7163.1109.3.9","article-title":"Differential sensitivity of cancer cells to docosahexaenoic acid-induced cytotoxicity: The potential importance of down-regulation of superoxide dismutase 1 expression","volume":"3","author":"Ding","year":"2004","journal-title":"Mol. Cancer Ther."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1158\/1535-7163.MCT-06-0608","article-title":"Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting cancer cells from docosahexaenoic acid-induced cytotoxicity","volume":"6","author":"Ding","year":"2007","journal-title":"Mol. Cancer Ther."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/j.freeradbiomed.2008.01.009","article-title":"Sensitization by docosahexaenoic acid (DHA) of breast cancer cells to anthracyclines through loss of glutathione peroxidase (GPx1) response","volume":"44","author":"Vibet","year":"2008","journal-title":"Free Radic. Biol. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4990","DOI":"10.1182\/blood-2002-08-2391","article-title":"Docosahexaenoic acid enhances arsenic trioxidemediated apoptosis in arsenic trioxide-resistant HL-60 cells","volume":"101","author":"Sturlan","year":"2003","journal-title":"Blood"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1017\/S000711451200308X","article-title":"Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway","volume":"109","author":"Granci","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/01635580802395725","article-title":"Growth inhibition and induction of apoptosis of colon cancer cell lines by applying marine phospholipid","volume":"61","author":"Hossain","year":"2009","journal-title":"Nutrition and Cancer"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1476-511X-12-71","article-title":"Effects of polyunsaturated fatty acids on the growth of gastric cancer cells in vitro","volume":"12","author":"Dai","year":"2013","journal-title":"Lipids Health Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e1524","DOI":"10.1038\/cddis.2014.477","article-title":"Docosahexaenoic acid induces the degradation of HPV E6\/E7 oncoproteins by activating the ubiquitin-proteasome system","volume":"5","author":"Jing","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Kang, K.S., Wang, P., Yamabe, N., Fukui, M., Jay, T., and Zhu, B.T. (2010). Docosahexaenoic acid induces apoptosis in MCF-7 cells in vitro and in vivo via reactive oxygen species formation and caspase 8 activation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010296"},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Zajdel, A., Wilczok, A., and Tarkowski, M. (2015). Toxic effects of n-3 polyunsaturated fatty acids in human lung A549 cells. Toxicol. Vitro.","DOI":"10.1016\/j.tiv.2015.09.013"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1084\/jem.20020760","article-title":"Resolvins: A family of bioactive products of \u03c9-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals","volume":"196","author":"Serhan","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"888","DOI":"10.2174\/1568026615666150827101602","article-title":"Anti-inflammatory and Pro-resolving effects of n-3 PUFA in Cancers: Structures and Mechanisms","volume":"16","author":"Wang","year":"2016","journal-title":"Curr. Top Med. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1593\/neo.10388","article-title":"Effect of eicosapentaenoic acid on E-type prostaglandin synthesis and EP4 receptor signaling in human colorectal cancer cells","volume":"12","author":"Hawcroft","year":"2010","journal-title":"Neoplasia"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Poorani, R., Bhatt, A.N., Dwarakanath, B.S., and Das, U.N. (2015). COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance. Eur. J. Pharmacol.","DOI":"10.1016\/j.ejphar.2015.08.049"},{"key":"ref_155","first-page":"1173","article-title":"The effects of dietary \u03c9\u22123 fatty acids on the DU-145 transplantable human prostatic tumor","volume":"17","author":"Karmali","year":"1987","journal-title":"Anticancer Res."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1093\/carcin\/9.4.603","article-title":"Effects of dietary menhaden oil and retinyl acetate on the growth of DU145 human prostatic adenocarcinoma cells transplanted into athymic nude mice","volume":"9","author":"Rose","year":"1988","journal-title":"Carcinogenesis"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1023\/A:1005971317978","article-title":"Dietary fat and breast cancer metastasis by human tumor xenografts","volume":"46","author":"Rose","year":"1997","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4662","DOI":"10.1158\/1078-0432.CCR-06-0459","article-title":"Effect of altering dietary \u03c9-6\/\u03c9-3 fatty acid ratios on prostate cancer membrane composition, cyclooxygenase-2, and prostaglandin E2","volume":"12","author":"Kobayashi","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1097\/MPA.0b013e31815ccc44","article-title":"Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth","volume":"36","author":"Funahashi","year":"2008","journal-title":"Pancreas"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1093\/carcin\/bgh252","article-title":"Effects of a combination of docosahexaenoic acid and 1,4-phenylene bis(methylene) selenocyanate on cyclooxygenase 2, inducible nitric oxide synthase and \u03b2-catenin pathways in colon cancer cells","volume":"25","author":"Narayanan","year":"2004","journal-title":"Carcinogenesis"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.2174\/092986707782793934","article-title":"n-3 polyunsaturated fatty acids and the prevention of colorectal cancer: Molecular mechanisms involved","volume":"14","author":"Calviello","year":"2007","journal-title":"Curr. Med. Chem."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2912","DOI":"10.1158\/0008-5472.CAN-07-2305","article-title":"Peroxisome proliferator-activated receptor \u03b3-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells","volume":"68","author":"Sun","year":"2008","journal-title":"Cancer Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"18441","DOI":"10.1074\/jbc.M802107200","article-title":"In vivo and in vitro regulation of syndecan 1 in prostate cells by n-3 polyunsaturated fatty acids","volume":"283","author":"Edwards","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"O\u2019Flaherty, J.T., Hu, Y., Wooten, R.E., Horita, D.A., Samuel, M.P., Thomas, M.J., Sun, H., and Edwards, I.J. (2012). 15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0045480"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1093\/carcin\/bgs324","article-title":"15-Lipoxygenase-1-mediated metabolism of docosahexaenoic acid is required for syndecan-1 signaling and apoptosis in prostate cancer cells","volume":"34","author":"Hu","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_166","first-page":"5075","article-title":"Microarray analysis of anti-cancer effects of docosahexaenoic acid on human colon cancer model in nude mice","volume":"8","author":"Zou","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"854","DOI":"10.2741\/4252","article-title":"\u03c9-3 PUFAs induce apoptosis of gastric cancer cells via ADORA1","volume":"19","author":"Sheng","year":"2014","journal-title":"Front. Biosci."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/5\/2\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:18:16Z","timestamp":1760210296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/5\/2\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,26]]},"references-count":167,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,2]]}},"alternative-id":["jcm5020015"],"URL":"https:\/\/doi.org\/10.3390\/jcm5020015","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,26]]}}}