Apoptosis as a Mechanism Involved in the Anticancer Effect of Dietary n-3 Polyunsaturated Fatty Acids

  • Simona Serini
  • Elena Fasano
  • Elisabetta Piccioni
  • Achille Renato Maria Cittadini
  • Gabriella Calviello
Chapter

Abstract

Increasing evidence has been accumulated in recent years that n-3 polyunsaturated fatty acids (PUFAs) may exert a chemopreventive and/or a chemotherapeutic role against the development and progression of several kinds of cancer. The antineoplastic properties of n-3 PUFAs seem to be strictly related to their ability to drive cancer cells towards apoptosis. In the present chapter we have critically analyzed the results that support apoptosis as the main cellular process involved in the anticancer effects of these fatty acids. We have also examined the molecular mechanisms that are affected by n-3 PUFAs and that have been considered involved the induction of apoptosis by these fatty acids. The pro-apoptotic effect has been examined in breast and colon cancer, the form of cancers more affected by these fatty acids, as well as in many other minor forms of cancers. On the whole, we show that the pro-apoptotic effect of n-3 PUFAs in cancer cells is well documented and strongly supported, and it is exerted through many different molecular mechanisms.

Keywords

Epidermal Grow Factor Receptor Colon Cancer Cell Gastric Cancer Cell Epidermal Grow Factor Receptor Activation Proapoptotic Effect 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Ailhaud G, Massiera F, Weill P, Legrand P, Alessandri JM, Guesnet P (2006) Temporal changes in dietary fats: role of n-6 polyunsaturated fatty acids in excessive adipose tissue development and relationship to obesity. Prog Lipid Res 45:203–236PubMedGoogle Scholar
  2. Alquobaili F, Miller SA, Muhie S, Day A, Jett M, Hammamieh R (2010) Estrogen receptor-dependent genomic expression profiles in breast cancer cells in response to fatty acids. J Carcinog 8:17PubMedGoogle Scholar
  3. Altenburg JD, Bieberich AA, Terry C, Harvey KA, Vanhorn JF, Xu Z, Jo Davisson V, Siddiqui RA (2011) A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone. BMC Cancer 11:149PubMedGoogle Scholar
  4. Anti M, Marra G, Armelao F, Bartoli GM, Ficarelli R, Percesepe A, De Vitis I, Maria G, Sofo L, Rapaccini GL et al (1992) Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. Gastroenterology 103:883–891PubMedGoogle Scholar
  5. Anti M, Armelao F, Marra G, Percesepe A, Bartoli GM, Palozza P, Parrella P, Canetta C, Gentiloni N, De Vitis I et al (1994) Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. Gastroenterology 107:1709–1718PubMedGoogle Scholar
  6. Ariel A, Serhan CN (2007) Resolvins and protectins in the termination program of acute inflammation. Trends Immunol 28:176–183PubMedGoogle Scholar
  7. Aronson WJ, Glaspy JA, Reddy ST, Reese D, Heber D, Bagga D (2001) Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer. Urology 58:283–288PubMedGoogle Scholar
  8. Bachmann IM, Straume O, Puntervoll HE, Kalvenes MB, Akslen LA (2005) Importance of P-cadherin, beta-catenin, and Wnt5a/frizzled for progression of melanocytic tumors and prognosis in cutaneous melanoma. Clin Cancer Res 11:8606–8614PubMedGoogle Scholar
  9. Bancroft LK, Lupton JR, Davidson LA, Taddeo SS, Murphy ME, Carroll RJ, Chapkin RS (2003) Dietary fish oil reduces oxidative DNA damage in rat colonocytes. Free Radic Biol Med 35:149–159PubMedGoogle Scholar
  10. Banerjee S, Li Y, Wang Z, Sarkar FH (2008) Multi-targeted therapy of cancer by genistein. Cancer Lett 269:226–242PubMedGoogle Scholar
  11. Barberger-Gateau P, Samieri C, Féart C, Plourde M (2011) Dietary omega 3 polyunsaturated fatty acids and Alzheimer’s disease: interaction with apolipoprotein E genotype. Curr Alzheimer Res 8:479–491PubMedGoogle Scholar
  12. Bartram HP, Gostner A, Scheppach W, Reddy BS, Rao CV, Dusel G, Richter F, Richter A, Kasper H (1993) Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects. Gastroenterology 105:1317–1322PubMedGoogle Scholar
  13. Baumgartner M, Sturlan S, Roth E, Wessner B, Bachleitner-Hofmann T (2004) Enhancement of arsenic trioxide-mediated apoptosis using docosahexaenoic acid in arsenic trioxide-resistant solid tumor cells. Int J Cancer 112:707–712PubMedGoogle Scholar
  14. Brown M, Bellon M, Nicot C (2007) Emodin and DHA potently increase arsenic trioxide interferon-alpha-induced cell death of HTLV-I-transformed cells by generation of reactive oxygen species and inhibition of Akt and AP-1. Blood 109:1653–1659PubMedGoogle Scholar
  15. Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:1505S–1519SPubMedGoogle Scholar
  16. Calviello G, Palozza P, Piccioni E, Maggiano N, Frattucci A, Franceschelli P, Bartoli GM (1998) Dietary supplementation with eicosapentaenoic and docosahexaenoic acid inhibits growth of Morris hepatocarcinoma 3924A in rats: effects on proliferation and apoptosis. Int J Cancer 75:699–705PubMedGoogle Scholar
  17. Calviello G, Palozza P, Maggiano N, Piccioni E, Franceschelli P, Frattucci A, Di Nicuolo F, Bartoli GM (1999) Cell proliferation, differentiation, and apoptosis are modified by n-3 polyunsaturated fatty acids in normal colonic mucosa. Lipids 34:599–604PubMedGoogle Scholar
  18. Calviello G, Palozza P, Di Nicuolo F, Maggiano N, Bartoli GM (2000) n-3 PUFA dietary supplementation inhibits proliferation and store-operated calcium influx in thymoma cells growing in Balb/c mice. J Lipid Res 41:182–189PubMedGoogle Scholar
  19. Calviello G, Di Nicuolo F, Gragnoli S, Piccioni E, Serini S, Maggiano N, Tringali G, Navarra P, Ranelletti FO, Palozza P (2004) n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and -2 and HIF-1alpha induction pathway. Carcinogenesis 25:2303–2310PubMedGoogle Scholar
  20. Calviello G, Di Nicuolo F, Serini S, Piccioni E, Boninsegna A, Maggiano N, Ranelletti FO, Palozza P (2005) Docosahexaenoic acid enhances the susceptibility of human colorectal cancer cells to 5-fluorouracil. Cancer Chemother Pharmacol 55:12–20PubMedGoogle Scholar
  21. Calviello G, Serini S, Palozza P (2006) n-3 polyunsaturated fatty acids as signal transduction modulators and therapeutical agents in cancer. Curr Signal Transduct Ther 1:255–271Google Scholar
  22. Calviello G, Resci F, Serini S, Piccioni E, Toesca A, Boninsegna A, Monego G, Ranelletti FO, Palozza P (2007a) Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2. Carcinogenesis 28:1202–1209PubMedGoogle Scholar
  23. Calviello G, Serini S, Piccioni E (2007b) n-3 polyunsaturated fatty acids and the prevention of colorectal cancer: molecular mechanisms involved. Curr Med Chem 14:3059–3069PubMedGoogle Scholar
  24. Calviello G, Serini S, Piccioni E (2008) Alzheimer’s disease and n-3 polyunsaturated fatty acids: beneficial effects and possible molecular pathways involved. Curr Signal Transduct Ther 3:152–157Google Scholar
  25. Calviello G, Serini S, Piccioni E, Pessina G (2009) Antineoplastic effects of n-3 polyunsaturated fatty acids in combination with drugs and radiotherapy: preventive and therapeutic strategies. Nutr Cancer 61:287–301PubMedGoogle Scholar
  26. Chajès V, Sattler W, Stranzl A, Kostner GM (1995) Influence of n-3 fatty acids on the growth of human breast cancer cells in vitro: relationship to peroxides and vitamin-E. Breast Cancer Res Treat 34:199–212PubMedGoogle Scholar
  27. Chang WL, Chapkin RS, Lupton JR (1998) Fish oil blocks azoxymethane-induced rat colon tumorigenesis by increasing cell differentiation and apoptosis rather than decreasing cell proliferation. J Nutr 128:491–497PubMedGoogle Scholar
  28. Chapkin RS, Davidson LD, Davidson LA (1992) Phospholipid molecular species composition of mouse liver nuclei. Influence of dietary n-3 fatty acid ethyl esters. Biochem J 287:237–240PubMedGoogle Scholar
  29. Chen ZY, Istfan NW (2000) Docosahexaenoic acid is a potent inducer of apoptosis in HT-29 colon cancer cells. Prostaglandins Leukot Essent Fatty Acids 63:301–308PubMedGoogle Scholar
  30. Cheng J, Ogawa K, Kuriki K, Yokoyama Y, Kamiya T, Seno K, Okuyama H, Wang J, Luo C, Fujii T, Ichikawa H, Shirai T, Tokudome S (2003) Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors. Cancer Lett 193:17–24PubMedGoogle Scholar
  31. Chien AJ, Moore EC, Lonsdorf AS, Kulikauskas RM, Rothberg BG, Berger AJ, Major MB, Hwang ST, Rimm DL, Moon RT (2009) Activated Wnt/beta-catenin signaling in melanoma is associated with decreased proliferation in patient tumors and a murine melanoma model. Proc Natl Acad Sci U S A 106:1193–1198PubMedGoogle Scholar
  32. Chiu LC, Wong EY, Ooi VE (2004) Docosahexaenoic acid from a cultured microalga inhibits cell growth and induces apoptosis by upregulating Bax/Bcl-2 ratio in human breast carcinoma MCF-7 cells. Ann N Y Acad Sci 1030:361–368PubMedGoogle Scholar
  33. Connolly JM, Gilhooly EM, Rose DP (1999) Effects of reduced dietary linoleic acid intake, alone or combined with an algal source of docosahexaenoic acid, on MDA-MB-231 breast cancer cell growth and apoptosis in nude mice. Nutr Cancer 35:44–49PubMedGoogle Scholar
  34. Corsetto PA, Montorfano G, Zava S, Jovenitti IE, Cremona A, Berra B, Rizzo AM (2011) Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane. Lipids Health Dis 10:73PubMedGoogle Scholar
  35. Courtney ED, Matthews S, Finlayson C, Di Pierro D, Belluzzi A, Roda E, Kang JY, Leicester RJ (2007) Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Colorectal Dis 22:765–776PubMedGoogle Scholar
  36. Cowing BE, Saker KE (2001) Polyunsaturated fatty acids and epidermal growth factor receptor/mitogen-activated protein kinase signaling in mammary cancer. J Nutr 131:1125–1128PubMedGoogle Scholar
  37. Cremonezzi DC, Díaz MP, Valentich MA, Eynard AR (2004) Neoplastic and preneoplastic lesions induced by melamine in rat urothelium are modulated by dietary polyunsaturated fatty acids. Food Chem Toxicol 42:1999–2007PubMedGoogle Scholar
  38. Danbara N, Yuri T, Tsujita-Kyutoku M, Sato M, Senzaki H, Takada H, Hada T, Miyazawa T, Okazaki K, Tsubura A (2004) Conjugated docosahexaenoic acid is a potent inducer of cell cycle arrest and apoptosis and inhibits growth of colo 201 human colon cancer cells. Nutr Cancer 50:71–79PubMedGoogle Scholar
  39. de Lima TM, Amarante-Mendes GP, Curi R (2007) Docosahexaenoic acid enhances the toxic effect of imatinib on Bcr-Abl expressing HL-60 cells. Toxicol In Vitro 21:1678–1685PubMedGoogle Scholar
  40. Ding WQ, Liu B, Vaught JL, Palmiter RD, Lind SE (2006) Clioquinol and docosahexaenoic acid act synergistically to kill tumor cells. Mol Cancer Ther 5:1864–1872PubMedGoogle Scholar
  41. Edwards IJ, Sun H, Hu Y, Berquin IM, O’Flaherty JT, Cline JM, Rudel LL, Chen YQ (2008) In vivo and in vitro regulation of syndecan 1 in prostate cells by n-3 polyunsaturated fatty acids. J Biol Chem 283:18441–18449PubMedGoogle Scholar
  42. Emoto M, Naganuma Y, Choijamts B, Ohno T, Yoshihisa H, Kanomata N, Kawarabayashi T, Aizawa M (2010) Novel chemoembolization usingcalcium-phosphate ceramic microsphere incorporating TNP-470, an antiangiogenic agent. Cancer Sci 101:984–990PubMedGoogle Scholar
  43. Erb P, Ji J, Kump E, Mielgo A, Wernli M (2008) Apoptosis and pathogenesis of melanoma and nonmelanoma skin cancer. Adv Exp Med Biol 624:283–295PubMedGoogle Scholar
  44. Fan YY, Zhan Y, Aukema HM, Davidson LA, Zhou L, Callaway E, Tian Y, Weeks BR, Lupton JR, Toyokuni S, Chapkin RS (2009) Proapoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of manganese-dependent superoxide dismutase knockout mice. J Nutr 139:1328–1332PubMedGoogle Scholar
  45. Fini L, Piazzi G, Ceccarelli C, Daoud Y, Belluzzi A, Munarini A, Graziani G, Fogliano V, Selgrad M, Garcia M, Gasbarrini A, Genta RM, Boland CR, Ricciardiello L (2010) Highly purified eicosapentaenoic acid as free fatty acids strongly suppresses polyps in Apc(Min/+) mice. Clin Cancer Res 16:5703–5711PubMedGoogle Scholar
  46. Finstad HS, Myhrstad MC, Heimli H, Lømo J, Blomhoff HK, Kolset SO, Drevon CA (1998) Multiplication and death-type of leukemia cell lines exposed to very long-chain polyunsaturated fatty acids. Leukemia 12:921–929PubMedGoogle Scholar
  47. Finstad HS, Dyrendal H, Myhrstad MC, Heimli H, Drevon CA (2000) Uptake and activation of eicosapentaenoic acid are related to accumulation of triacylglycerol in Ramos cells dying from apoptosis. J Lipid Res 41:554–563PubMedGoogle Scholar
  48. Ge Y, Chen Z, Kang ZB, Cluette-Brown J, Laposata M, Kang JX (2002) Effects of adenoviral gene transfer of C. elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells. Anticancer Res 22:537–543PubMedGoogle Scholar
  49. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM (2006) n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 83:1526S–1535SPubMedGoogle Scholar
  50. Ghosh N, Chaki R, Mandal V, Mandal SC (2010) COX-2 as a target for cancer chemotherapy. Pharmacol Rep 62:233–244PubMedGoogle Scholar
  51. Ghosh-Choudhury T, Mandal CC, Woodruff K, St Clair P, Fernandes G, Choudhury GG, Ghosh-Choudhury N (2009) Fish oil targets PTEN to regulate NFkappaB for downregulation of anti-apoptotic genes in breast tumor growth. Breast Cancer Res Treat 118:213–228PubMedGoogle Scholar
  52. Gleissman H, Yang R, Martinod K, Lindskog M, Serhan CN, Johnsen JI, Kogner P (2010) Docosahexaenoic acid metabolome in neural tumors: identification of cytotoxic intermediates. FASEB J 24:906–915PubMedGoogle Scholar
  53. Goto K, Tanaka Y, Matsumoto Y, Ueoka R (2008) Induction of apoptosis of human tumor cells by hybrid liposomes including docosahexaenoic acid. Bioorg Med Chem Lett 18:1880–1883PubMedGoogle Scholar
  54. Guillèn MD, Goicoechea E (2008) Toxic oxygenated alpha, beta-unsaturated aldehydes and their study in foods: a review. Crit Rev Food Sci Nutr 48:119–136PubMedGoogle Scholar
  55. Hammamieh R, Chakraborty N, Miller SA, Waddy E, Barmada M, Das R, Peel SA, Day AA, Jett M (2007) Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells. Breast Cancer Res Treat 101:7–16PubMedGoogle Scholar
  56. Hardy SC, Kleinman RE (1994) Fat and cholesterol in the diet of infants and young children: implications for growth, development, and long-term health. J Pediatr 125:S69–S77PubMedGoogle Scholar
  57. Hawcroft G, D’Amico M, Albanese C, Markham AF, Pestell RG, Hull MA (2002) Indomethacin induces differential expression of beta-catenin, gamma-catenin and T-cell factor target genes in human colorectal cancer cells. Carcinogenesis 23:107–114PubMedGoogle Scholar
  58. Hawcroft G, Loadman PM, Belluzzi A, Hull MA (2010) Effect of eicosapentaenoic acid on E-type prostaglandin synthesis and EP4 receptor signaling in human colorectal cancer cells. Neoplasia 12:618–627PubMedGoogle Scholar
  59. Hilakivi-Clarke L, Olivo SE, Shajahan A, Khan G, Zhu Y, Zwart A, Cho E, Clarke R (2005) Mechanisms mediating the effects of prepubertal (n-3) polyunsaturated fatty acid diet on breast cancer risk in rats. J Nutr 135:2946S–2952SPubMedGoogle Scholar
  60. Hites RA, Foran JA, Schwager SJ, Knuth BA, Hamilton MC, Carpenter DO (2004) Global assessment of polybrominated diphenyl ethers in farmed and wild salmon. Environ Sci Technol 38:4945–4949PubMedGoogle Scholar
  61. Hofmanová J, Vaculová A, Kozubík A (2005) Polyunsaturated fatty acids sensitize human colon adenocarcinoma HT-29 cells to death receptor-mediated apoptosis. Cancer Lett 218:33–41PubMedGoogle Scholar
  62. Holman RT (1986) Control of polyunsaturated acids in tissue lipids. J Am Coll Nutr 5:183–211PubMedGoogle Scholar
  63. Holoch PA, Griffith TS (2009) TNF-related apoptosis-inducing ligand (TRAIL): a new path to anti-cancer therapies. Eur J Pharmacol 625:63–72PubMedGoogle Scholar
  64. Hong MY, Lupton JR, Morris JS, Wang N, Carroll RJ, Davidson LA, Elder RH, Chapkin RS (2000) Dietary fish oil reduces O6-methylguanine DNA adduct levels in rat colon in part by increasing apoptosis during tumor initiation. Cancer Epidemiol Biomarkers Prev 9:819–826PubMedGoogle Scholar
  65. Hong SH, Kim J, Kim JM, Lee SY, Shin DS, Son KH, Han DC, Sung YK, Kwon BM (2007) Apoptosis induction of 2′-hydroxycinnamaldehyde as a proteasome inhibitor is associated with ER stress and mitochondrial perturbation in cancer cells. Biochem Pharmacol 74:557–565PubMedGoogle Scholar
  66. Hu Y, Sun H, Owens RT, Gu Z, Wu J, Chen YQ, O’Flaherty JT, Edwards IJ (2010) Syndecan-1-dependent suppression of PDK1/Akt/bad signaling by docosahexaenoic acid induces apoptosis in prostate cancer. Neoplasia 12:826–836PubMedGoogle Scholar
  67. Huang YC, Jessup JM, Forse RA, Flickner S, Pleskow D, Anastopoulos HT, Ritter V, Blackburn GL (1996) n-3 fatty acids decrease colonic epithelial cell proliferation in high-risk bowel mucosa. Lipids 31:S313–S317PubMedGoogle Scholar
  68. Igarashi M, Ma K, Chang L, Bell JM, Rapoport SI (2008) Rat heart cannot synthesize docosahexaenoic acid from circulating alpha-linolenic acid because it lacks elongase-2. J Lipid Res 49:1735–1745PubMedGoogle Scholar
  69. Inki P, Jalkanen M (1996) The role of syndecan-1 in malignancies. Ann Med 28:63–67PubMedGoogle Scholar
  70. Ion G, Akinsete JA, Hardman WE (2010) Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1) TAg mice offspring. BMC Cancer 10:81PubMedGoogle Scholar
  71. Jakobsen CH, Størvold GL, Bremseth H, Follestad T, Sand K, Mack M, Olsen KS, Lundemo AG, Iversen JG, Krokan HE, Schønberg SA (2008) DHA induces ER stress and growth arrest in human colon cancer cells: associations with cholesterol and calcium homeostasis. J Lipid Res 49:2089–2100PubMedGoogle Scholar
  72. Jordan A, Stein J (2003) Effect of an omega-3 fatty acid containing lipid emulsion alone and in combination with 5-fluorouracil (5-FU) on growth of the colon cancer cell line Caco-2. Eur J Nutr 42:324–331PubMedGoogle Scholar
  73. Kakar P, Watson T, Lip GY (2008) New approaches to therapy with omega-3 fatty acids. Curr Atheroscler Rep 10:79–87PubMedGoogle Scholar
  74. Kang JX (2007) Fat-1 transgenic mice: a new model for omega-3 research. Prostaglandins Leukot Essent Fatty Acids 77:263–267PubMedGoogle Scholar
  75. Kang KS, Wang P, Yamabe N, Fukui M, Jay T, Zhu BT (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:e10296PubMedGoogle Scholar
  76. Kello M, Mikes J, Jendzelovský R, Koval J, Fedorocko P (2010) PUFAs enhance oxidative stress and apoptosis in tumour cells exposed to hypericin-mediated PDT. Photochem Photobiol Sci 9:1244–1251PubMedGoogle Scholar
  77. Kim JY, Park HD, Park E, Chon JW, Park YK (2009) Growth-inhibitory and proapoptotic effects of alpha-linolenic acid on estrogen-positive breast cancer cells. Ann N Y Acad Sci 1171:190–195PubMedGoogle Scholar
  78. Kolar SS, Barhoumi R, Callaway ES, Fan YY, Wang N, Lupton JR, Chapkin RS (2007a) Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca(2+) accumulation in colonocytes. Am J Physiol Gastrointest Liver Physiol 293:G935–G943PubMedGoogle Scholar
  79. Kolar SS, Barhoumi R, Lupton JR, Chapkin RS (2007b) Docosahexaenoic acid and butyrate synergistically induce colonocyte apoptosis by enhancing mitochondrial Ca2+ accumulation. Cancer Res 67:5561–5568PubMedGoogle Scholar
  80. Kris-Etherton PM, Hill AM (2008) N-3 fatty acids: food or supplements? J Am Diet Assoc 108:1125–1130PubMedGoogle Scholar
  81. Kuan CY, Walker TH, Luo PG, Chen CF (2011) Long-chain polyunsaturated fatty acids promote paclitaxel cytotoxicity via inhibition of the MDR1 gene in the human colon cancer Caco-2 cell line. J Am Coll Nutr 30:265–273PubMedGoogle Scholar
  82. Lands WE (1992) Biochemistry and physiology of n-3 fatty acids. FASEB J 6:2530–2536PubMedGoogle Scholar
  83. Latham P, Lund EK, Johnson IT (1999) Dietary n-3 PUFA increases the apoptotic response to 1,2-dimethylhydrazine, reduces mitosis and suppresses the induction of carcinogenesis in the rat colon. Carcinogenesis 20:645–650PubMedGoogle Scholar
  84. Lee SE, Lim JW, Kim H (2009) Activator protein-1 mediates docosahexaenoic acid-induced apoptosis of human gastric cancer cells. Ann N Y Acad Sci 1171:163–169PubMedGoogle Scholar
  85. Li H, Liu L, David ML, Whitehead CM, Chen M, Fetter JR, Sperl GJ, Pamukcu R, Thompson WJ (2002) Pro-apoptotic actions of exisulind and CP461 in SW480 colon tumor cells involve beta-catenin and cyclin D1 down-regulation. Biochem Pharmacol 64:1325–1336PubMedGoogle Scholar
  86. Liebersbach BF, Sanderson RD (1994) Expression of syndecan-1 inhibits cell invasion into type I collagen. J Biol Chem 269:20013–20019PubMedGoogle Scholar
  87. Lim K, Han C, Dai Y, Shen M, Wu T (2009) Omega-3 polyunsaturated fatty acids inhibit hepatocellular carcinoma cell growth through blocking beta-catenin and cyclooxygenase-2. Mol Cancer Ther 8:3046–3055PubMedGoogle Scholar
  88. Lindskog M, Gleissman H, Ponthan F, Castro J, Kogner P, Johnsen JI (2006) Neuroblastoma cell death in response to docosahexaenoic acid: sensitization to chemotherapy and arsenic-induced oxidative stress. Int J Cancer 118:2584–2593PubMedGoogle Scholar
  89. Llor X, Pons E, Roca A, Alvarez M, Mañé J, Fernández-Bañares F, Gassull MA (2003) The effects of fish oil, olive oil, oleic acid and linoleic acid on colorectal neoplastic processes. Clin Nutr 22:71–79PubMedGoogle Scholar
  90. Lou YR, Peng QY, Li T, Medvecky CM, Lin Y, Shih WJ, Conney AH, Shapses S, Wagner GC, Lu YP (2011) Effects of high-fat diets rich in either omega-3 or omega-6 fatty acids on UVB-induced skin carcinogenesis in SKH-1 mice. Carcinogenesis 32:1078–1084PubMedGoogle Scholar
  91. Lu Y, Feskens EJ, Dollé ME, Imholz S, Verschuren WM, Müller M, Boer JM (2010a) Dietary n-3 and n-6 polyunsaturated fatty acid intake interacts with FADS1 genetic variation to affect total and HDL-cholesterol concentrations in the Doetinchem Cohort Study. Am J Clin Nutr 92:258–265PubMedGoogle Scholar
  92. Lu IF, Hasio AC, Hu MC, Yang FM, Su HM (2010b) Docosahexaenoic acid induces proteasome-dependent degradation of estrogen receptor alpha and inhibits the downstream signaling target in MCF-7 breast cancer cells. J Nutr Biochem 21:512–517PubMedGoogle Scholar
  93. Lukiw WJ, Cui JG, Marcheselli VL, Bodker M, Botkjaer A, Gotlinger K, Serhan CN, Bazan NG (2005) A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease. J Clin Invest 115:2774–2783PubMedGoogle Scholar
  94. Ma DW, Ngo V, Huot PS, Kang JX (2006) N-3 polyunsaturated fatty acids endogenously synthesized in fat-1 mice are enriched in the mammary gland. Lipids 41:35–39PubMedGoogle Scholar
  95. Madden J, Williams CM, Calder PC, Lietz G, Miles EA, Cordell H, Mathers JC, Minihane AM (2011) The impact of common gene variants on the response of biomarkers of cardiovascular disease (CVD) risk to increased fish oil fatty acids intakes. Annu Rev Nutr 31:203–234PubMedGoogle Scholar
  96. Mammoto T, Mukai M, Mammoto A, Yamanaka Y, Hayashi Y, Mashimo T, Kishi Y, Nakamura H (2002) Intravenous anesthetic, propofol inhibits invasion of cancer cells. Cancer Lett 184:165–170PubMedGoogle Scholar
  97. Manna S, Janarthan M, Ghosh B, Rana B, Rana A, Chatterjee M (2010) Fish oil regulates cell proliferation, protect DNA damages and decrease HER-2/neu and c-Myc protein expression in rat mammary carcinogenesis. Clin Nutr 29:531–537PubMedGoogle Scholar
  98. McCann JC, Ames BN (2005) Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals. Am J Clin Nutr 82:281–295PubMedGoogle Scholar
  99. Menendez JA, Mehmi I, Atlas E, Colomer R, Lupu R (2004) Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: role of exogenous dietary fatty acids, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB. Int J Oncol 24:591–608PubMedGoogle Scholar
  100. Menendez JA, Lupu R, Colomer R (2005) Exogenous supplementation with omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA; 22:6n-3) synergistically enhances taxane cytotoxicity and downregulates Her-2/neu (c-erbB-2) oncogene expression in human breast cancer cells. Eur J Cancer Prev 14:263–270PubMedGoogle Scholar
  101. Menéndez JA, Vázquez-Martín A, Ropero S, Colomer R, Lupu R (2006) HER2 (erbB-2)-targeted effects of the omega-3 polyunsaturated fatty acid, alpha-linolenic acid (ALA; 18:3n-3), in breast cancer cells: the “fat features” of the “Mediterranean diet” as an “anti-HER2 cocktail”. Clin Transl Oncol 8:812–820PubMedGoogle Scholar
  102. Merendino N, Loppi B, D’Aquino M, Molinari R, Pessina G, Romano C, Velotti F (2005) Docosahexaenoic acid induces apoptosis in the human PaCa-44 pancreatic cancer cell line by active reduced glutathione extrusion and lipid peroxidation. Nutr Cancer 52:225–233PubMedGoogle Scholar
  103. Morris MC (2006) Docosahexaenoic acid and Alzheimer disease. Arch Neurol 63:1527–1528PubMedGoogle Scholar
  104. Mukherjee PK, Chawla A, Loayza MS, Bazan NG (2007) Docosanoids are multifunctional regulators of neural cell integrity and fate: significance in aging and disease. Prostaglandins Leukot Essent Fatty Acids 77:233–238PubMedGoogle Scholar
  105. Nakagawa H, Yamamoto D, Kiyozuka Y, Tsuta K, Uemura Y, Hioki K, Tsutsui Y, Tsubura A (2000) Effects of genistein and synergistic action in combination with eicosapentaenoic acid on the growth of breast cancer cell lines. J Cancer Res Clin Oncol 126:448–454PubMedGoogle Scholar
  106. Narayanan BA, Narayanan NK, Reddy BS (2001) Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. Int J Oncol 19:1255–1262PubMedGoogle Scholar
  107. Narayanan NK, Narayanan BA, Reddy BS (2005) A combination of docosahexaenoic acid and celecoxib prevents prostate cancer cell growth in vitro and is associated with modulation of nuclear factor-kappaB, and steroid hormone receptors. Int J Oncol 26:785–792PubMedGoogle Scholar
  108. NCT00253643 (2011) Fish oil and green tea extract in preventing prostate cancer in patients who are at risk for developing prostate cancer. OHSU Knight Cancer Institute. From: http://clinicaltrials.gov. Retrieved Dec 2011
  109. NCT00402285 (2011) Lycopene or omega-3 fatty acid nutritional supplements in treating patients with stage I or stage II prostate cancer. University of California, San Francisco. From: http://clinicaltrials.gov. Retrieved Dec 2011
  110. NCT00433797 (2011) Dietary intervention with phytochemicals and polyunsaturated fatty acids in prostate cancer patients. University of Oslo. From: http://clinicaltrials.gov. Retrieved Dec 2011
  111. NCT00458549 (2011) Polyunsaturated fatty acids in treating patients with prostate cancer undergoing prostate biopsy and/or surgery. Dana-Farber Cancer Institute. From: http://clinicaltrials.gov. Retrieved Dec 2011
  112. NCT00627276 (2011) Omega-3 fatty acids in treating women with newly diagnosed ductal carcinoma in situ and/or atypical ductal hyperplasia. OHSU Knight Cancer Institute. From: http://clinicaltrials.gov. Retrieved Dec 2011
  113. NCT00798876 (2011) Low-fat fish oil diet for prostate cancer prevention. University of California, Los Angeles. From: http://clinicaltrials.gov. Retrieved Dec 2011
  114. NCT00996749 (2011) Omega-3 fatty acids in treating patients with advanced prostate cancer. Wake Forest University. From: http://clinicaltrials.gov. Retrieved Dec 2011
  115. NCT01070355 (2011) Eicosapentaenoic acid (EPA) for treatment of colorectal cancer liver metastases (EMT). University of Leeds. From: http://clinicaltrials.gov. Retrieved Dec 2011
  116. NCT00723398 (2012) Nutritional supplements and hormonal manipulations for breast cancer prevention. Penn State University. From: http://clinicaltrials.gov. Retrieved Jan 2012
  117. Notarnicola M, Messa C, Refolo MG, Tutino V, Miccolis A, Caruso MG (2011) Polyunsaturated fatty acids reduce fatty acid synthase and hydroxy-methyl-glutaryl CoA-reductase gene expression and promote apoptosis in HepG2 cell line. Lipids Health Dis 10:10PubMedGoogle Scholar
  118. Olivo SE, Hilakivi-Clarke L (2005) Opposing effects of prepubertal low- and high-fat n-3 polyunsaturated fatty acid diets on rat mammary tumorigenesis. Carcinogenesis 26:1563–1572PubMedGoogle Scholar
  119. Pan J, Keffer J, Emami A, Ma X, Lan R, Goldman R, Chung FL (2009) Acrolein-derived DNA adduct formation in human colon cancer cells: its role in apoptosis induction by docosahexaenoic acid. Chem Res Toxicol 22:798–806PubMedGoogle Scholar
  120. Petrik MB, McEntee MF, Johnson BT, Obukowicz MG, Whelan J (2000) Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice. J Nutr 130:2434–2443PubMedGoogle Scholar
  121. Phillips CM, Goumidi L, Bertrais S, Field MR, Ordovas JM, Cupples LA, Defoort C, Lovegrove JA, Drevon CA, Blaak EE, Gibney MJ, Kiec-Wilk B, Karlstrom B, Lopez-Miranda J, McManus R, Hercberg S, Lairon D, Planells R, Roche HM (2010) Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults. J Nutr 140:238–244PubMedGoogle Scholar
  122. Pot GK, Majsak-Newman G, Geelen A, Harvey LJ, Nagengast FM, Witteman BJ, van de Meeberg PC, Timmer R, Tan A, Wahab PJ, Hart AR, Williams MP, Przybylska-Phillips K, Dainty JR, Schaafsma G, Kampman E, Lund EK, FISHGASTRO Study Group (2009) Fish consumption and markers of colorectal cancer risk: a multicenter randomized controlled trial. Am J Clin Nutr 90:354–361PubMedGoogle Scholar
  123. Rao GN, Ney E, Herbert RA (2000) Effect of melatonin and linolenic acid on mammary cancer in transgenic mice with c-neu breast cancer oncogene. Breast Cancer Res Treat 64:287–296PubMedGoogle Scholar
  124. Rapraeger AC (2001) Molecular interactions of syndecans during development. Semin Cell Dev Biol 12:107–116PubMedGoogle Scholar
  125. Reddy BS, Maruyama H (1986) Effect of dietary fish oil on azoxymethane-induced colon carcinogenesis in male F344 rats. Cancer Res 46:3367–3370PubMedGoogle Scholar
  126. Rogers KR, Kikawa KD, Mouradian M, Hernandez K, McKinnon KM, Ahwah SM, Pardini RS (2010) Docosahexaenoic acid alters epidermal growth factor receptor-related signaling by disrupting its lipid raft association. Carcinogenesis 31:1523–1530PubMedGoogle Scholar
  127. Ruxton CH, Reed SC, Simpson MJ, Millington KJ (2007) The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. J Hum Nutr Diet 20:275–285PubMedGoogle Scholar
  128. Samuelsson B, Dahlén SE, Lindgren JA, Rouzer CA, Serhan CN (1987) Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science 237:1171–1176PubMedGoogle Scholar
  129. Saugstad LF (2006) Are neurodegenerative disorder and psychotic manifestations avoidable brain dysfunctions with adequate dietary omega-3? Nutr Health 18:89–101PubMedGoogle Scholar
  130. Schimmer AD (2011) Clioquinol – a novel copper-dependent and independent proteasome inhibitor. Curr Cancer Drug Targets 11:325–331Google Scholar
  131. Schley PD, Jijon HB, Robinson LE, Field CJ (2005) Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells. Breast Cancer Res Treat 92:187–195PubMedGoogle Scholar
  132. Schley PD, Brindley DN, Field CJ (2007) (n-3) PUFA alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells. J Nutr 137:548–553PubMedGoogle Scholar
  133. Sengupta S, Muir JG, Gibson PR (2006) Does butyrate protect from colorectal cancer? J Gastroenterol Hepatol 21:209–218PubMedGoogle Scholar
  134. Serini S, Trombino S, Oliva F, Piccioni E, Monego G, Resci F, Boninsegna A, Picci N, Ranelletti FO, Calviello G (2008) Docosahexaenoic acid induces apoptosis in lung cancer cells by increasing MKP-1 and down-regulating p-ERK1/2 and p-p38 expression. Apoptosis 13:1172–1183PubMedGoogle Scholar
  135. Serini S, Piccioni E, Merendino N, Calviello G (2009) Dietary polyunsaturated fatty acids as inducers of apoptosis: implications for cancer. Apoptosis 14:135–152PubMedGoogle Scholar
  136. Serini S, Piccioni E, Rinaldi C, Mostra D, Damiani G, Calviello G (2010) Fish from an artificial lake: n-3 PUFA content and chemical-physical and ecological features of the lake. J Food Compost Anal 23:133–141Google Scholar
  137. Serini S, Donato V, Piccioni E, Trombino S, Monego G, Toesca A, Innocenti I, Missori M, De Spirito M, Celleno L, Fasano E, Ranelletti FO, Calviello G (2011a) Docosahexaenoic acid reverts resistance to UV-induced apoptosis in human keratinocytes: involvement of COX-2 and HuR. J Nutr Biochem 22:874–885PubMedGoogle Scholar
  138. Serini S, Fasano E, Piccioni E, Cittadini AR, Calviello G (2011b) Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits and potential harmful effects. Chem Res Toxicol 24:2093–2105PubMedGoogle Scholar
  139. Serini S, Fasano E, Piccioni E, Cittadini AR, Calviello G (2011c) Differential anti-cancer effects of purified EPA and DHA and possible mechanisms involved. Curr Med Chem 18:4065–4075PubMedGoogle Scholar
  140. Serini S, Fasano E, Piccioni E, Monego G, Cittadini AR, Celleno L, Ranelletti FO, Calviello G (2012) DHA induces apoptosis and differentiation in human melanoma cells in vitro: involvement of HuR-mediated COX-2 mRNA stabilization and β-catenin nuclear translocation. Carcinogenesis 33:164–173PubMedGoogle Scholar
  141. Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58:362–366PubMedGoogle Scholar
  142. Shoemaker AR, Gould KA, Luongo C, Moser AR, Dove WF (1997) Studies of neoplasia in the Min mouse. Biochim Biophys Acta 1332:F25–F48PubMedGoogle Scholar
  143. Siddiqui RA, Zerouga M, Wu M, Castillo A, Harvey K, Zaloga GP, Stillwell W (2005) Anticancer properties of propofol-docosahexaenoate and propofol-eicosapentaenoate on breast cancer cells. Breast Cancer Res 7:R645–R654PubMedGoogle Scholar
  144. Simopoulos AP (2006) Evolutionary aspects of diet, the omega-6/omega-3 ratio and genetic variation: nutritional implications for chronic diseases. Biomed Pharmacother 60:502–507PubMedGoogle Scholar
  145. Slagsvold JE, Pettersen CH, Størvold GL, Follestad T, Krokan HE, Schønberg SA (2010) DHA alters expression of target proteins of cancer therapy in chemotherapy resistant SW620 colon cancer cells. Nutr Cancer 62:611–621PubMedGoogle Scholar
  146. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A (2009) The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer 45:2077–2086PubMedGoogle Scholar
  147. Sprecher H, Luthria DL, Mohammed BS, Baykousheva SP (1995) Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J Lipid Res 36:2471–2477PubMedGoogle Scholar
  148. Stene LC, Thorsby PM, Berg JP, Rønningen KS, Joner G, Norwegian Childhood Diabetes Study Group (2008) Peroxisome proliferator-activated receptor-gamma2 Pro12Ala polymorphism, cod liver oil and risk of type 1 diabetes. Pediatr Diabetes 9:40–45Google Scholar
  149. Stern MC, Butler LM, Corral R, Joshi AD, Yuan JM, Koh WP, Yu MC (2009) Polyunsaturated fatty acids, DNA repair single nucleotide polymorphisms and colorectal cancer in the Singapore Chinese Health Study. J Nutrigenet Nutrigenomics 2:273–279PubMedGoogle Scholar
  150. Stillwell W, Shaikh SR, Zerouga M, Siddiqui R, Wassall SR (2005) Docosahexaenoic acid affects cell signaling by altering lipid rafts. Reprod Nutr Dev 45:559–579PubMedGoogle Scholar
  151. Stoll BA (2002) N-3 fatty acids and lipid peroxidation in breast cancer inhibition. Br J Nutr 87:193–198PubMedGoogle Scholar
  152. Strouch MJ, Ding Y, Salabat MR, Melstrom LG, Adrian K, Quinn C, Pelham C, Rao S, Adrian TE, Bentrem DJ, Grippo PJ (2011) A high omega-3 fatty acid diet mitigates murine pancreatic precancer development. J Surg Res 165:75–81PubMedGoogle Scholar
  153. Sturlan S, Baumgartner M, Roth E, Bachleitner-Hofmann T (2003) Docosahexaenoic acid enhances arsenic trioxide-mediated apoptosis in arsenic trioxide-resistant HL-60 cells. Blood 101:4990–4997PubMedGoogle Scholar
  154. Sun H, Berquin IM, Edwards IJ (2005) Omega-3 polyunsaturated fatty acids regulate syndecan-1 expression in human breast cancer cells. Cancer Res 65:4442–4447PubMedGoogle Scholar
  155. Sun H, Berquin IM, Owens RT, O’Flaherty JT, Edwards IJ (2008) Peroxisome proliferator-activated receptor gamma-mediated up-regulation of syndecan-1 by n-3 fatty acids promotes apoptosis of human breast cancer cells. Cancer Res 68:2912–2919PubMedGoogle Scholar
  156. Sun H, Hu Y, Gu Z, Owens RT, Chen YQ, Edwards IJ (2011a) Omega-3 fatty acids induce apoptosis in human breast cancer cells and mouse mammary tissue through syndecan-1 inhibition of the MEK-Erk pathway. Carcinogenesis 32:1518–1524PubMedGoogle Scholar
  157. Sun H, Hu Y, Gu Z, Wilson MD, Chen YQ, Rudel LL, Willingham MC, Edwards IJ (2011b) Endogenous synthesis of n-3 polyunsaturated fatty acids in Fat-1 mice is associated with increased mammary gland and liver syndecan-1. PLoS One 6:e20502PubMedGoogle Scholar
  158. Thomas X, Troncy J (2009) Arsenic: a beneficial therapeutic poison – a historical overview. Adler Mus Bull 35:3–13PubMedGoogle Scholar
  159. Thompson MD, Monga SP (2007) WNT/beta-catenin signaling in liver health and disease. Hepatology 45:1298–1305PubMedGoogle Scholar
  160. Thompson LU, Chen JM, Li T, Strasser-Weippl K, Goss PE (2005) Dietary flaxseed alters tumor biological markers in postmenopausal breast cancer. Clin Cancer Res 11:3828–3835PubMedGoogle Scholar
  161. Toit-Kohn JL, Louw L, Engelbrecht AM (2009) Docosahexaenoic acid induces apoptosis in colorectal carcinoma cells by modulating the PI3 kinase and p38 MAPK pathways. J Nutr Biochem 20:106–114PubMedGoogle Scholar
  162. Trifan OC, Hla T (2003) Cyclooxygenase-2 modulates cellular growth and promotes tumorigenesis. J Cell Mol Med 7:207–222PubMedGoogle Scholar
  163. Tsujii M, DuBois RN (1995) Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83:493–501PubMedGoogle Scholar
  164. Tsujita-Kyutoku M, Yuri T, Danbara N, Senzaki H, Kiyozuka Y, Uehara N, Takada H, Hada T, Miyazawa T, Ogawa Y, Tsubura A (2004) Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action. Breast Cancer Res 6:R291–R299PubMedGoogle Scholar
  165. Vaculová A, Hofmanová J, Andera L, Kozubík A (2005) TRAIL and docosahexaenoic acid cooperate to induce HT-29 colon cancer cell death. Cancer Lett 229:43–48PubMedGoogle Scholar
  166. Vanamala J, Glagolenko A, Yang P, Carroll RJ, Murphy ME, Newman RA, Ford JR, Braby LA, Chapkin RS, Turner ND, Lupton JR (2008) Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3. Carcinogenesis 29:790–796PubMedGoogle Scholar
  167. Volcik KA, Nettleton JA, Ballantyne CM, Boerwinkle E (2008) Peroxisome proliferator-activated receptor [alpha] genetic variation interacts with n-6 and long-chain n-3 fatty acid intake to affect total cholesterol and LDL-cholesterol concentrations in the Atherosclerosis Risk in Communities Study. Am J Clin Nutr 87:1926–1931PubMedGoogle Scholar
  168. von Schacky C (2007) n-3 PUFA in CVD: influence of cytokine polymorphism. Proc Nutr Soc 66:166–170Google Scholar
  169. Wei N, Wang B, Zhang QY, Mi MT, Zhu JD, Yu XP, Yuan JL, Chen K, Wang J, Chang H (2008) Effects of different dietary fatty acids on the fatty acid compositions and the expression of lipid metabolic-related genes in mammary tumor tissues of rats. Nutr Cancer 60:810–825PubMedGoogle Scholar
  170. Wei G, Rafiyath S, Liu D (2010) First-line treatment for chronic myeloid leukemia: dasatinib, nilotinib, or imatinib. J Hematol Oncol 3:47PubMedGoogle Scholar
  171. West NJ, Clark SK, Phillips RK, Hutchinson JM, Leicester RJ, Belluzzi A, Hull MA (2010) Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut 59:918–925PubMedGoogle Scholar
  172. Wu M, Harvey KA, Ruzmetov N, Welch ZR, Sech L, Jackson K, Stillwell W, Zaloga GP, Siddiqui RA (2005) Omega-3 polyunsaturated fatty acids attenuate breast cancer growth through activation of a neutral sphingomyelinase-mediated pathway. Int J Cancer 117:340–348PubMedGoogle Scholar
  173. Yamagami T, Porada CD, Pardini RS, Zanjani ED, Almeida-Porada G (2009) Docosahexaenoic acid induces dose dependent cell death in an early undifferentiated subtype of acute myeloid leukemia cell line. Cancer Biol Ther 8:331–337PubMedGoogle Scholar
  174. Yamamoto D, Kiyozuka Y, Adachi Y, Takada H, Hioki K, Tsubura A (1999) Synergistic action of apoptosis induced by eicosapentaenoic acid and TNP-470 on human breast cancer cells. Breast Cancer Res Treat 55:149–160PubMedGoogle Scholar
  175. Yee LD, Young DC, Rosol TJ, Vanbuskirk AM, Clinton SK (2005) Dietary (n-3) polyunsaturated fatty acids inhibit HER-2/neu-induced breast cancer in mice independently of the PPARgamma ligand rosiglitazone. J Nutr 135:983–988PubMedGoogle Scholar
  176. Yin Y, Zhan WH, Peng JS, Zhao ZG (2007) Apoptosis of human gastric cancer cells induced by omega-3 polyunsaturated fatty acids. Zhonghua Wei Chang Wai Ke Za Zhi 10:570–573PubMedGoogle Scholar
  177. Zand H, Rahimipour A, Salimi S, Shafiee SM (2008) Docosahexaenoic acid sensitizes Ramos cells to gamma-irradiation-induced apoptosis through involvement of PPAR-gamma activation and NF-kappaB suppression. Mol Cell Biochem 317:113–120PubMedGoogle Scholar
  178. Zhuo Z, Zhang L, Mu Q, Lou Y, Gong Z, Shi Y, Ouyang G, Zhang Y (2009) The effect of combination treatment with docosahexaenoic acid and 5-fluorouracil on the mRNA expression of apoptosis-related genes, including the novel gene BCL2L12, in gastric cancer cells. In Vitro Cell Dev Biol Anim 45:69–74PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Simona Serini
    • 1
  • Elena Fasano
    • 1
  • Elisabetta Piccioni
    • 1
  • Achille Renato Maria Cittadini
    • 1
  • Gabriella Calviello
    • 1
  1. 1.Institute of General PathologyUniversità Cattolica del S. CuoreRomeItaly

Personalised recommendations