Anticancer Effect of Fish Oil – a Fable or the Truth?

Authors: J. Neuwirthová;  B. Gál;  P. Smilek;  P. Urbánková;  R. Kostřica
Authors‘ workplace: Klinika otorinolaryngologie a chirurgie hlavy a krku LF MU a FN u sv. Anny v Brně
Published in: Klin Onkol 2016; 29(2): 100-106
Category: Review
doi: 10.14735/amko2016100


Omega-3 fatty acids from fish oil have several health benefits for cancer patients. Recent findings indicate that, besides their well-known anti-cachectic effect, they can act synergistically with chemotherapeutic agents and may enhance tumor radio-sensitivity. The mechanisms underlying their anti-tumor effects are complex. The following effects have been reported after administration of omega-3 fatty acids: increased lipid peroxidation during therapy; disturbed tumor receptor signal pathways; lower levels level of pro-inflammatory cytokines that induce tumor cell proliferation; promotion of apoptosis in tumor tissues; immune modulation; and changes in hormonal metabolism. Epidemiological and experimental evidence support the conjecture that fish oil has an anticancer benefit for both animals and humans. However, Western countries have a diet rich in omega-6 fatty acids, which interfere with the health benefits of omega-3 fatty acids because they compete for the same rate-limiting enzymes. For this reason, the consumption of omega-6 fatty acids in Western diet needs to be lowered to observe the anti-tumor effect of omega-3 fatty acids. Some epidemiological studies report conflicting results, which may be explained by inconsistencies in the methodologies employed.

Key words:
omega-3 fatty acid – fish oil – chemoprevention – anticancer agent – apoptosis – lipid peroxidation

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

6. 11. 2015

9. 1. 2016


1. Zadák Z, Tichá A, Hronek M et al. Pokroky v metabolizmu a výživě 2011 a cesta k personalizované léčbě. Vnitr Lek 2011; 57(11): 970– 974.

2. Aktas BH, Chorev M, Halperin JA. Cancer and n-3 PUFAs: the translations initiation connection. In: Milner JA, Romagnolo DF (eds). Nutrition and health: bio­active compounds and cancer. Springer 2010: 253– 273.

3. Ziegler RG, Hoover RN, Pike MC et al. Migration patterns and breast cancer risk in Asian American women. J Natl Cancer Inst 1993; 85(22): 1819– 1827.

4. Deapen D, Liu L, Perkins C et al. Rapidly rising breast cancer incidence rates among Asian-American women. Int J Cancer 2002; 99(5): 747– 750.

5. Nielsen NH, Hansen JP. Breast cancer in Greenland-selected epidemiological, clinical, and histological features. J Cancer Res Clin Oncol 1980; 98(3): 287– 299.

6. Terry PD, Rohan TE, Wolk A. Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence. Am J Clin Nutr 2003; 77(3): 532– 543.

7. Lanier AP, Kelly JJ, Smith B et al. Alaska Native cancer update: incidence rates 1989– 1993. Cancer Epidemiol Biomarkers Prev 1996; 5(9): 749– 751.

8. Tsuji K, Harashima E, Nakagawa Y et al. Time-lag effect of dietary fiber and fat intake ratio on Japanese colon cancer mortality. Biomed Environ Sci 1996; 9(2– 3): 223– 228.

9. You WC, Jin F, Devesa S et al. Rapid increase in colorectal cancer rates in urban Shanghai, 1972– 97, in relation to dietary changes. J Cancer Epidemiol Prev 2002; 7(3): 143– 146.

10. Thiebaut AC, Chajes V, Gerber M et al. Dietary intakes of omega-6 and omega-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer 2009; 124(4): 924– 931. doi: 10.1002/ijc.23980.

11. Weylandt KH, Serini S, Chen YQ et al. Omega-3 polyunsaturated fatty acids: the way forward in times of mixed evidence. Biomed Res Int 2015; 2015: 143109. doi: 10.1155/ 2015/143109.

12. Gerber M. Omega-3 fatty acids and cancers: a systematic update review of epidemiological stud­ies. Br J Nutr 2012; 107 (Suppl 2): S228– S239. doi: 10.1017/S0007114512001614.

13. Devi KP, Rajavel T, Russo GL et al. Molecular targets of omega-3 fatty acids for cancer therapy. Anticancer Agents Med Chem 2015; 15(7): 888– 895.

14. Mitchell DC, Niu SL, Litman BJ. DHA-rich phospholipids optimize G-protein-coupled signaling. J Pediatr 2003; 143 (Suppl 4): S80– S86.

15. Wong SW, Kwon MJ, Choi AM et al. Fatty acids modulate toll-like receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner. J Biol Chem 2009; 284(40): 27384– 27392. doi: 10.1074/jbc.M109.044065.

16. Xiao YF, Ke Q, Wang SY et al. Single point mutations affect fatty acid block of human myocardial sodium chan­nel alpha subunit Na+ channels. Proc Natl Acad Sci U S A 2001; 98(6): 3606– 3611.

17. Schley PD, Brindley DN, Field CJ. (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr 2007; 137(3): 548– 553.

18. Corsetto PA, Montorfano G, Zava S et al. Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane. Lipids Health Dis 2011; 10: 73. doi: 10.1186/1476-511X-10-73.

19. Rogers KR, Kikawa KD, Mouradian M et al. Docosahexaenoic acid alters epidermal growth factor receptor­related signaling by disrupting itslipid raft association. Carcinogenesis 2010; 31(9): 1523– 1530. doi: 10.1093/carcin/bgq111.

20. Edwards IJ, O‘Flaherty JT. Omega-3 fatty acids and PPARgamma in cancer. PPAR Res 2008; 2008: 358052. doi: 10.1155/2008/358052.

21. Zhang YW, Morita I, Yao XS et al. Pretreatment with eicosapentaenoic acid prevented hypoxia/ reoxygenation-induced abnormality in endothelial gap junctional intercellular communication through inhibiting the tyrosine kinase activity. Prostaglandins Leukot Essent Fatty Acids 1999; 61(1): 33– 40.

22. Stephenson JA, Al-Taan O, Arshad A et al. The multifaceted effects of omega-3 polyunsaturated fatty acids on the hallmarks of cancer. J Lipids 2013; 2013: 261247. doi: 10.1155/2013/261247.

23. Palakurthi SS, Flückiger R, Aktas H et al. Inhibition of translation initiation mediates the anticancer effect of the n-3 polyunsaturated fatty acid eicosapentaenoic acid. Cancer Res 2000; 60(11): 2919– 2925.

24. Aktas H, Halperin JA. Translational regulation of gene expression by omega-3 fatty acids. J Nutr 2004; 134 (Suppl 9): 2487S– 2491S.

25. Mandal CC, Ghosh-Choudhury T, Dey N et al. miR-21 is targeted by omega-3 polyunsaturated fatty acid to regulate breast tumor CSF-1 expression. Carcinogenesis 2012; 33(10): 1897– 1908. doi: 10.1093/carcin/bgs198.

26. Yao QH, Zhang XC, Fu T et al. ω-3 polyunsaturated fatty acids inhibit the proliferation of the lung adenocarcinoma cell line A549 in vitro. Mol Med Rep 2014; 9(2): 401– 406. doi: 10.3892/mmr.2013.1829.

27. Lu Y, Nie D, Witt WT et al. Expression of the fat-1 gene diminishes prostate cancer growth in vivo through enhancing apoptosis and inhibiting GSK-3 beta phosphorylation. Mol Cancer Ther 2008; 7(10): 3203– 3211. doi: 10.1158/1535-7163.MCT-08-0494.

28. Jakobsen CH, Størvold GL, Bremseth H et al. DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis. J Lipid Res 2008; 49(10): 2089– 2100. doi: 10.1194/jlr.M700389-JLR200.

29. Xue M, Wang Q, Zhao J et al. Docosahexaenoic acid inhibited the Wnt/ beta-catenin pathway and suppressed breast cancer cells in vitro and in vivo. J Nutr Biochem 2014; 25(2): 104– 110. doi: 10.1016/j.jnutbio­.2013.09.008.

30. Song KS, Jing K, Kim JS et al. Omega-3-polyunsaturated fatty acids suppress pancreatic cancer cell growth in vitro and in vivo via downregulation of Wnt/ Beta-catenin signaling. Pancreatology 2011; 11(6): 574– 584. doi: 10.1159/000334468.

31. Lim K, Han C, Xu L et al. Cyclooxygenase-2-derived prostaglandin E2 activates beta-catenin in human cholangiocarcinoma cells: evidence for inhibition of these signaling pathways by omega 3 polyunsaturated fatty acids. Cancer Res 2008; 68(2): 553– 560. doi: 10.1158/0008-5472.CAN-07-2295.

32. Rose DP, Rayburn J, Hatala MA et al. Effects of dietary fish oil on fatty acids and eicosanoids in metasta­sizing human breast cancer cells. Nutr Cancer 1994; 22(2): 131– 141.

33. Rose DP, Connolly JM. Omega-3 fatty acids as cancer chemopreventive agents. Pharmacol Ther 1999; 83(3): 217– 244.

34. Park JM, Kwon SH, Han YM et al. Omega-3 polyunsaturated fatty acids as potential chemopreventive agent for gastrointestinal cancer. J Cancer Prev 2013; 18(3): 201– 208.

35. Evans JF, Kargman SL. Cancer and cyclooxygenase-2 (COX-2) inhibition. Curr Pharm Des 2004; 10(6): 627– 634.

36. Donnini S, Finetti F, Solito R et al. EP2 prostanoid receptor promotes squamous cell carcinoma growth through epidermal growth factor receptor transactivation and iNOS and ERK1/2 pathways. FASEB J 2007; 21(10): 2418– 2430.

37. Shao J, Evers BM, Sheng H. Prostaglandin E2 synergistically enhances receptor tyrosine kinase-dependent signaling system in colon cancer cells. J Biol Chem 2004; 279(14): 14287– 14293.

38. Chun KS, Lao HC, Trempus CS et al. The prostaglandin receptor EP2 activates multiple signaling pathways and beta-arrestin1 complex formation during mouse skin papilloma development. Carcinogenesis 2009; 30(9): 1620– 1627. doi: 10.1093/carcin/bgp168.

39. Vara-Messler M, Buccellati C, Pustina L et al. Potential role of PUFAs and COXIBs in cancer chemoprevention. Prostaglandins Other Lipid Media 2015; 120: 97– 102. doi: 10.1016/j.prostaglandins.2015.04.003.

40. Yang P, Jiang Y, Fischer SM. Prostaglandin E3 metabolism and cancer. Cancer Lett 2014; 348(1– 2): 1– 11. doi: 10.1016/j.canlet.2014.03.010.

41. Spencer L, Mann C, Metcalfe M et al. The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer 2009; 45(12): 2077– 2086. doi: 10.1016/j.ejca.2009.04.026.

42. Kang JX, Liu A. The role of the tissue omega-6/omega-3 fatty acid ratio in regulating tumor angiogenesis. Cancer Metastasis Rev 2013; 32(1– 2): 201– 210. doi: 10.1007/s10555-012-9401-9.

43. El-Sohemy A, Archer MC. Regulation of mevalonate synthesis in rat mammary glands by dietary n-3 and n-6 polyunsaturated fatty acids. Cancer Res 1997; 57(17): 3685– 3687.

44. Duncan RE, El-Sohemy A, Archer MC. Dietary factors and the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for breast cancer and development. Mol Nutr Food Res 2005; 49(2): 93– 100.

45. Osborne CK. Effects of estrogens and antiestrogens on cell proliferation: Implications for the treatment of breast cancer. Cancer Treat Res 1988; 39: 111– 129.

46. Liang T, Liao S. Inhibition of steroid 5 alpha-reductase by specific aliphatic unsaturated fatty acids. Biochem J1992; 285(2): 557– 562.

47. Ferguson BJ, Hudson WR, McCarty KS Jr. Sex steroid receptor distribution in the human larynx and laryngeal carcinoma. Arch Otolaryngol Head Neck Surg 1987; 113(12): 1311– 1315.

48. Kleemann D, Kunkel S. Serum dihydrotestosterone versus total testosterone values of patients with laryngeal carcinomas and chronic laryngitis. Laryngorhinootologie 1996; 75(6): 351– 355.

49. Remenár É, Számel I, Buda B et al. ‚ Why men?‘ Hormones and hormone receptors in male head and neck cancer patients. In: Klainsasser O, Glanz H, Olofsson J (eds). Advances in Laryngology in Europe. J Elsevier 1997: 137– 140.

50. Lukits J, Remenár E, Rásó E et al. Molecular identification, expression and prognostic role of estrogen- and progesterone receptors in head and neck cancer. Int J Oncol 2007; 30(1): 155– 160.

51. Yoo HJ, Sepkovic DW, Bradlow HL et al. Estrogen metabolism as a risk factor for head and neck cancer. Otolaryngol Head Neck Surg 2011; 124(3): 241– 247.

52. Shatalova EG, Klein-Szanto AJ, Devarajan K et al. Estrogen and cytochrome P450 1B1 contribute to both early- and late-stage head and neck carcinogenesis. Cancer Prev Res 2011; 4(1): 107– 115. doi: 10.1158/1940-6207.CAPR-10-0133.

53. Kapoor S. Immunomodulatory properties of omega-3 fatty acids: a possible explanation for their systemic, anticarcinogenic effects. J Leukoc Biol 2009; 85(1): 2– 3. doi: 10.1189/jlb.0708456.

54. Correia M, Michel V, Matos AA et al. Docosahexaenoic acid inhibits Helicobacter pylori growth in vitro and mice gastric mucosa colonization. PLoS One 2012; 7(4): e35072. doi: 10.1371/journal.pone.0035072.

55. Thompson L, Cockayne A, Spiller RC. Inhibitory effect of polyunsaturated fatty acids on the growth of Helicobacter pylori: a possible explanation of the effect of diet on peptic ulceration. Gut 1994; 35(11): 1557– 1561.

56. Park SH, Kangwan N, Park JM et al. Non-microbial ap­proach for Helicobacter pylori as faster track to prevent gastric cancer than simple eradication. World J Gastroenterol 2013; 19(47): 8986– 8995. doi: 10.3748/wjg.v19.i47.8986.

57. Gonzalez MJ. Fish oil, lipid peroxidation and mammary tumor growth. J Am Coll Nutr 1995; 14(4): 325– 335.

58. Hardman WE, Munoz J Jr, Cameron IL. Role of lipid peroxidation and antioxidant enzymes in omega 3 fatty acids induced suppression of breast cancer xenograft growth in mice. Cancer Cell Int 2002; 2(1): 10.

59. Cai F, Sorg O, Granci V et al. Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two dif­ferent colorectal cancer cell lines. Clin Nutr 2014; 33(1): 164– 170. doi: 10.1016/j.clnu.2013.04.005.

60. Kikawa KD, Herrick JS, Tateo RE et al. Induced oxidative stress and cell death in the A549 lung adenocarcinoma cell line by ionizing radiation is enhanced by supplementation with docosahexaenoic acid. Nutr Cancer 2010; 62(8): 1017– 1024. doi: 10.1080/01635581.2010.492084.

61. Jeong S, Jing K, Kim N et al. Docosahexaenoic acid-induced apoptosis is mediated by activation of mitogen-activated protein kinases in human cancer cells. BMC Cancer 2014; 14: 481. doi: 10.1186/1471-2407-14-481.

62. Fukui M, Kang KS, Okada K et al. EPA, an omega-3 fatty acid, induces apoptosis in human pancreatic cancer cells: role of ROS accumulation, caspase-8 activation, and autophagy induction. J Cell Biochem 2013; 114(1): 192– 203. doi: 10.1002/jcb.24354.

63. Binkova H, Smardova J, Krpensky A et al. Prognoza nadoru hlavy a krku se zamerenim na nadorovy supresor p53. Otorinolaryng Foniat 2004; 4: 189– 195.

64. Shin S, Jing K, Jeong S et al. The omega-3 polyunsaturated fatty acid DHA induces simultaneous apoptosis and autophagy via mitochondrial ROS-mediated Akt-mTOR signaling in prostate cancer cells expressing mutant p53. Biomed Res Int 2013; 2013: 568671. doi: 10.1155/ 2013/568671.

65. Gonzalez MJ, Schemmel RA, Dugan L Jr et al. Dietary fish oil inhibits human breast carcinoma growth: a function of increased lipid peroxidation. Lipids 1993; 28(9): 827– 832.

66. Hardman WE. (n-3) fatty acids and cancer therapy. J Nutr 2004; 134 (Suppl 12): 3427S– 3430S.

67. Abulrob AN, Mason M, Bryce R et al. The effect of fatty acids and analogues upon intracellular levels of doxorubicin in cells displaying P-glycoprotein mediated multidrug resistance. J Drug Target 2000; 8(4): 247– 256.

68. Abdia J, Garssena J, Faberb J et al. Omega-3 fatty acids, EPA and DHA induce apoptosis and enhance drug sensitivity in multiple myeloma cells but not in normal peripheral mononuclear cells. J Nutr Biochem 2014; 25(12): 1254– 1262. doi: 10.1016/j.jnutbio­.2014.06.013.

69. De Carlo F, Witte TR, Hardman WE et al. Omega-3 eicosapentaenoic acid decreases CD133 colon cancer stem-like cell marker expression while increasing sensitivity to chemotherapy. PLoS One 2013; 8(7): e69760. doi: 10.1371/journal.pone.0069760.

70. Vasudevan A, Yu Y, Banerjee S et al. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer. Cancer Prev Res (Phila) 2014; 7(11): 1138– 1148. doi: 10.1158/1940-6207.CAPR-14-0177.

71. Manni A, El-Bayoumy K, Skibinski CG et al. Combination of atiestrogens and omega-3 fatty acids for breast cancer prevention. Biomed Res Int 2015; 2015: 638645. doi: 10.1155/2015/638645.

72. Bougnoux P, Hajjaji N, Ferrasson MN et al. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial. Br J Cancer 2009; 101(12): 1978– 1985. doi: 10.1038/sj.bjc.6605441.

73. Yamagami T, Porada CD, Pardini RS et al. Docosahexaenoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line. Cancer Biol Ther 2009; 8(4): 331– 337.

74. Hering J, Garrean S, Dekoj TR et al. Inhibition of proliferation by omega-3 fatty acids in chemoresistant pancreatic cancer cells. Ann Surg Oncol 2007; 14(12): 3620– 3628.

75. Rogers KR, Kikawa KD, Mouradian M et al. Docosahexaenoic acid alters epidermal growth factor receptorrelated signaling by disrupting its lipid raft association. Carcinogenesis 2010; 31(9): 1523– 1530.

76. Dyari HR, Rawling T, Burget K et al. Synthetic omega-3 epoxyfatty acids as antiproliferative and pro-apoptotic agents in human breast cancer cells. J Med Chem 2014; 57(17): 7459– 7464. doi: 10.1021/jm501083y.

77. Malá E, Vejražková E, Bielmeierová J et al. Dlouhodobé sledování nutričního, klinického stavu a kvality života u nemocných s rakovinou hlavy a krku. Klin Onkol 2015; 28(3): 200– 214. doi: 10.14735/amko2015200.

78. Fiala J, Derflerová Brázdová Z. Výživa v prevenci nádorových onemocnění. Klin Onkol 2000; 13(speciál 2000): 8– 16.

79. Klener P. Chemoprevence nádorových onemocnění. Klin Onkol 1999; 12(3): 78– 81.

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