Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms.

Increasing evidence from animal and in vitro studies indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, present in fatty fish and fish oils inhibit carcinogenesis. The epidemiologic data on the association between fish consumption, as a surrogate marker for n-3 fatty acid intake, and cancer risk are, however, somewhat less consistent. This review highlights current knowledge of the potential mechanisms of the anticarcinogenic actions of n-3 fatty acids. Moreover, a possible explanation of why some epidemiologic studies failed to find an association between n-3 fatty acid intake and cancer risk is provided. Several molecular mechanisms whereby n-3 fatty acids may modify the carcinogenic process have been proposed. These include suppression of arachidonic acid-derived eicosanoid biosynthesis; influences on transcription factor activity, gene expression, and signal transduction pathways; alteration of estrogen metabolism; increased or decreased production of free radicals and reactive oxygen species; and mechanisms involving insulin sensitivity and membrane fluidity. Further studies are needed to evaluate and verify these mechanisms in humans to gain more understanding of the effects of n-3 fatty acid intake on cancer risk.

[1]  J. Mitchell,et al.  Prostaglandins and the regulation of tumor growth. , 2002, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[2]  E. Riboli,et al.  Consumption of Meat, Animal Products, Protein, and Fat and Risk of Breast Cancer: A Prospective Cohort Study in New York , 1994, Epidemiology.

[3]  J. Tímár,et al.  Fatty acid modulation of tumor cell adhesion to microvessel endothelium and experimental metastasis. , 1992, Prostaglandins.

[4]  A. Charlett,et al.  Fat, fish, fish oil and cancer. , 1996, British Journal of Cancer.

[5]  Christopher Y. Lu,et al.  Docosahexaenoic acid, a constituent of fetal and neonatal serum, inhibits nitric oxide production by murine macrophages stimulated by IFNγ plus LPS, or by IFNγ plus Listeria monocytogenes , 1998 .

[6]  C. la Vecchia,et al.  Intake of selected foods and nutrients and breast cancer risk: an age- and menopause-specific analysis. , 1997, Nutrition and cancer.

[7]  L Bohlin,et al.  Cox-2 inhibitory effects of naturally occurring and modified fatty acids. , 2001, Journal of natural products.

[8]  A. Dannenberg,et al.  Chemoprevention of colorectal cancer through inhibition of cyclooxygenase-2. , 1999, Seminars in oncology.

[9]  L. Baur,et al.  Fatty acids, triglycerides and syndromes of insulin resistance. , 1997, Prostaglandins, leukotrienes, and essential fatty acids.

[10]  Y. Nakaya,et al.  Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemi , 2002, British Journal of Nutrition.

[11]  A. Fields,et al.  Elevated protein kinase C betaII is an early promotive event in colon carcinogenesis. , 2001, Cancer research.

[12]  M. Anti,et al.  Effect of omega-3 fatty acids on rectal mucosal cell proliferation in subjects at risk for colon cancer. , 1992, Gastroenterology.

[13]  R. Heine,et al.  Dietary supplementation of omega-3 polyunsaturated fatty acids improves insulin sensitivity in non-insulin-dependent diabetes. , 1987, Diabetes research.

[14]  M. Sugano,et al.  Effect of dietary n−3 polyunsaturated fatty acids on cholesterol synthesis and degradation in rats of different ages , 2006, Lipids.

[15]  A. Grothey,et al.  Cyclooxygenase-2: a novel target for cancer chemotherapy? , 2001, Journal of Cancer Research and Clinical Oncology.

[16]  L. Frøyland,et al.  Chronic administration of eicosapentaenoic acid and docosahexaenoic acid as ethyl esters reduced plasma cholesterol and changed the fatty acid composition in rat blood and organs , 1996, Lipids.

[17]  E. Šeböková,et al.  HMG-CoA reductase activity in the liver of rats with hereditary hypertriglyceridemia: effect of dietary fish oil. , 1994, Endocrine regulations.

[18]  H. Okuyama,et al.  Dietary fatty acids--the N-6/N-3 balance and chronic elderly diseases. Excess linoleic acid and relative N-3 deficiency syndrome seen in Japan. , 1996, Progress in lipid research.

[19]  J. Lupton,et al.  Biochemical and Molecular Roles of Nutrients Fish Oil Blocks Azoxymethane-Induced Rat Colon Tumorigenesis by Increasing Cell Differentiation and Apoptosis Rather Than Decreasing Cell Proliferation , 1998 .

[20]  K. Honn,et al.  Mechanisms controlling cell cycle arrest and induction of apoptosis after 12-lipoxygenase inhibition in prostate cancer cells. , 2002, Cancer research.

[21]  K. Mayer,et al.  Regulatory potential of n-3 fatty acids in immunological and inflammatory processes , 2002, British Journal of Nutrition.

[22]  E. Rimm,et al.  A prospective study of intake of fish and marine fatty acids and prostate cancer. , 2003, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[23]  R. Schild,et al.  The Activity of PPAR in Primary Human Trophoblasts Is Enhanced by Oxidized Lipids , 2002 .

[24]  B. Spiegelman,et al.  PPARgamma : a nuclear regulator of metabolism, differentiation, and cell growth. , 2001, The Journal of biological chemistry.

[25]  A. El-Sohemy,et al.  Regulation of mevalonate synthesis in low density lipoprotein receptor knockout mice fed n-3 or n-6 polyunsaturated fatty acids , 1999, Lipids.

[26]  K. Bogen,et al.  Methods for estimating heterocyclic amine concentrations in cooked meats in the US diet. , 2001, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[27]  A. Tarnawski,et al.  PGE(2) stimulates VEGF expression in endothelial cells via ERK2/JNK1 signaling pathways. , 2001, Biochemical and biophysical research communications.

[28]  J. Cooke,et al.  Nitric oxide and angiogenesis. , 2002, Circulation.

[29]  S. Moncada,et al.  Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects. , 1993, Gastroenterology.

[30]  Michael J Thun,et al.  Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. , 2002, Journal of the National Cancer Institute.

[31]  S. Vermunt,et al.  Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C-alpha-linolenic acid. , 2000, Lipids.

[32]  W. Lands,et al.  Inhibition of prostaglandin biosynthesis by eicosapentaenoic acid. , 1979, Prostaglandins and medicine.

[33]  J. Masferrer,et al.  Cyclooxygenase-2 inhibition by celecoxib reduces proliferation and induces apoptosis in angiogenic endothelial cells in vivo. , 2002, Cancer research.

[34]  B. Evers,et al.  The role of NF-κB/IκB proteins in cancer: implications for novel treatment strategies , 1999 .

[35]  B. Spiegelman,et al.  Terminal differentiation of human breast cancer through PPAR gamma. , 1998, Molecular cell.

[36]  H Kesteloot,et al.  An ecological study of the relationship between dietary fat intake and breast cancer mortality. , 1993, Preventive medicine.

[37]  M. Thornquist,et al.  Types of dietary fat and the incidence of cancer at five sites. , 1990, Preventive medicine.

[38]  M. Carey,et al.  Down-Regulation of prostate-specific antigen expression by ligands for peroxisome proliferator-activated receptor gamma in human prostate cancer. , 2000, Cancer research.

[39]  Ho-Jin Park,et al.  3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Interfere With Angiogenesis by Inhibiting the Geranylgeranylation of RhoA , 2002, Circulation research.

[40]  B. Spiegelman,et al.  Loss-of-function mutations in PPAR gamma associated with human colon cancer. , 1999, Molecular cell.

[41]  H P Koeffler,et al.  Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. , 1998, Cancer research.

[42]  Daniel L. McGee,et al.  Ornithine decarboxylase and polyamines in colorectal neoplasia and mucosa. , 1993, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[43]  B. Spiegelman,et al.  Loss-of-Function Mutations in PPARγ Associated with Human Colon Cancer , 1999 .

[44]  N. Espat,et al.  NF-κB inhibition by ω-3 fatty acids modulates LPS-stimulated macrophage TNF-α transcription , 2003 .

[45]  P. Wong,et al.  Cyclooxygenase-2 Regulates Apoptosis in Rat Epididymis Through Prostaglandin D21 , 2002, Biology of reproduction.

[46]  N. Espat,et al.  NF-kappa B inhibition by omega -3 fatty acids modulates LPS-stimulated macrophage TNF-alpha transcription. , 2003, American journal of physiology. Lung cellular and molecular physiology.

[47]  E. Corey,et al.  Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[48]  Jian-Kang Chen,et al.  Epoxyeicosatrienoic Acids and Their Sulfonimide Derivatives Stimulate Tyrosine Phosphorylation and Induce Mitogenesis in Renal Epithelial Cells* , 1998, The Journal of Biological Chemistry.

[49]  村田 雅弘 Dual action of eicosapentaenoic acid in hepatoma cells : Up-regulation of metabolic action of insulin and inhibition of cell proliferation , 2001 .

[50]  K. Saker,et al.  Polyunsaturated fatty acids and epidermal growth factor receptor/mitogen-activated protein kinase signaling in mammary cancer. , 2001, The Journal of nutrition.

[51]  A. Fields,et al.  Overexpression of Protein Kinase C βII Induces Colonic Hyperproliferation and Increased Sensitivity to Colon Carcinogenesis , 1999, The Journal of cell biology.

[52]  G A Colditz,et al.  Relation of meat, fat, and fiber intake to the risk of colon cancer in a prospective study among women. , 1990, The New England journal of medicine.

[53]  R. Karmali n‐3 fatty acids and cancer , 1989, Journal of internal medicine. Supplement.

[54]  H. Tsuda,et al.  Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung. , 1997, British Journal of Cancer.

[55]  P. Calder,et al.  Fatty acids and lymphocyte functions , 2002, British Journal of Nutrition.

[56]  A. El-Sohemy,et al.  The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands. , 1998, Carcinogenesis.

[57]  G A Colditz,et al.  Association of dietary intake of fat and fatty acids with risk of breast cancer. , 1999, JAMA.

[58]  R. Jackson,et al.  Prostate cancer risk and consumption of fish oils: a dietary biomarker-based case–control study , 1999, British Journal of Cancer.

[59]  N. Boyd,et al.  Fish consumption and breast cancer risk: an ecological study. , 1989, Nutrition and cancer.

[60]  J. Hibbeln,et al.  Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans. , 2001, Journal of lipid research.

[61]  J. Marsh,et al.  Effect of omega-3 fatty acids on growth of a rat mammary tumor. , 1984, Journal of the National Cancer Institute.

[62]  É. Szabó,et al.  Enhanced growth inhibition by combination differentiation therapy with ligands of peroxisome proliferator-activated receptor-gamma and inhibitors of histone deacetylase in adenocarcinoma of the lung. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[63]  K. Rowe,et al.  Effects of interaction of RRR-alpha-tocopheryl acetate and fish oil on low-density-lipoprotein oxidation in postmenopausal women with and without hormone-replacement therapy. , 1996, The American journal of clinical nutrition.

[64]  E. Germain,et al.  Suppression of the promoter effect of polyunsaturated fatty acids by the absence of dietary vitamin E in experimental mammary carcinoma. , 1997, Cancer letters.

[65]  P. Spagnuolo,et al.  Tumor cell-endothelial cell interactions: evidence for roles for lipoxygenase products of arachidonic acid in metastasis. , 1997, Prostaglandins, leukotrienes, and essential fatty acids.

[66]  Rajnish A. Gupta,et al.  15S-Hydroxyeicosatetraenoic acid activates peroxisome proliferator-activated receptor gamma and inhibits proliferation in PC3 prostate carcinoma cells. , 2001, Cancer research.

[67]  A. Minihane,et al.  Effect of altered dietary n-3 fatty acid intake upon plasma lipid fatty acid composition, conversion of [13C]α-linolenic acid to longer-chain fatty acids and partitioning towards β-oxidation in older men , 2003, British Journal of Nutrition.

[68]  H. Bartsch,et al.  High dietary omega-6 polyunsaturated fatty acids drastically increase the formation of etheno-DNA base adducts in white blood cells of female subjects. , 1997, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[69]  B. Stoll n-3 Fatty acids and lipid peroxidation in breast cancer inhibition , 2002, British Journal of Nutrition.

[70]  D. Kroetz,et al.  Cytochrome P450 pathways of arachidonic acid metabolism , 2002, Current opinion in lipidology.

[71]  A. Marcus,et al.  Dietary n-3 fatty acids accelerate catabolism of leukotriene B4 in human granulocytes. , 1993, Biochimica et biophysica acta.

[72]  M. Leppert,et al.  Meat consumption, genetic susceptibility, and colon cancer risk: a United States multicenter case-control study. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[73]  A. Fields,et al.  Protein kinase C (cid:2) II and TGF (cid:2) RII in (cid:3) -3 fatty acid– mediated inhibition of colon carcinogenesis , 2002 .

[74]  Jian-Kang Chen,et al.  Cytochrome P450 Epoxygenase Metabolism of Arachidonic Acid Inhibits Apoptosis , 2001, Molecular and Cellular Biology.

[75]  P. van’t Veer,et al.  Adipose tissue omega-3 and omega-6 fatty acid content and breast cancer in the EURAMIC study. European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer. , 1998, American journal of epidemiology.

[76]  P. Palozza,et al.  Effects of different doses of fish oil on rectal cell proliferation in patients with sporadic colonic adenomas. , 1994, Gastroenterology.

[77]  R. Gibson,et al.  Simple relationships exist between dietary linoleate and the n-6 fatty acids of human neutrophils and plasma. , 1993, The American journal of clinical nutrition.

[78]  M. A. Lindner,et al.  A fish oil diet inhibits colon cancer in mice. , 1991, Nutrition and cancer.

[79]  R. Goldbohm,et al.  Animal products, calcium and protein and prostate cancer risk in the Netherlands Cohort Study , 1999, British Journal of Cancer.

[80]  Keiji Wakabayashi,et al.  Suppression of nitric oxide production in lipopolysaccharide-stimulated macrophage cells by omega 3 polyunsaturated fatty acids. , 1997, Japanese journal of cancer research : Gann.

[81]  W. Harris,et al.  n-3 fatty acids and serum lipoproteins: animal studies. , 1997, The American journal of clinical nutrition.

[82]  E. Diamandis,et al.  Health aspects of partially defatted flaxseed, including effects on serum lipids, oxidative measures, and ex vivo androgen and progestin activity: a controlled crossover trial. , 1999, The American journal of clinical nutrition.

[83]  William A. Pryor,et al.  The kinetics of the autoxidation of polyunsaturated fatty acids , 1987, Lipids.

[84]  H. Bartsch,et al.  Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. , 1999, Carcinogenesis.

[85]  F. Cianchi,et al.  Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. , 2001, Gastroenterology.

[86]  P. Calder,et al.  Polyunsaturated fatty acids, inflammation, and immunity , 2001, Lipids.

[87]  P. Ferrari,et al.  N‐3 and N‐6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case‐control study in Tours, France , 2002, International journal of cancer.

[88]  M. Katan,et al.  Linoleic acid intake and cancer risk: a review and meta-analysis. , 1998, The American journal of clinical nutrition.

[89]  N. Tajima,et al.  Effect of highly purified eicosapentaenoic acid ethyl ester on insulin resistance and hypertension in Dahl salt-sensitive rats. , 1999, Metabolism: clinical and experimental.

[90]  T. Adrian,et al.  12‐lipoxygenase metabolite 12(S)‐HETE stimulates human pancreatic cancer cell proliferation via protein tyrosine phosphorylation and ERK activation , 2001, International journal of cancer.

[91]  J. Berger,et al.  The mechanisms of action of PPARs. , 2002, Annual review of medicine.

[92]  R. Miller,et al.  Transcription of the murine iNOS gene is inhibited by docosahexaenoic acid, a major constituent of fetal and neonatal sera as well as fish oils , 1996, The Journal of experimental medicine.

[93]  M. Willingham,et al.  Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells. , 1999, Carcinogenesis.

[94]  M. Laville,et al.  Eicosapentaenoic acid induces mRNA expression of peroxisome proliferator-activated receptor gamma. , 2002, Obesity research.

[95]  C. la Vecchia,et al.  Diet and ovarian cancer risk: A case‐control study in Italy , 2001, International journal of cancer.

[96]  S. Lippman,et al.  15-LOX-1: a novel molecular target of nonsteroidal anti-inflammatory drug-induced apoptosis in colorectal cancer cells. , 2000, Journal of the National Cancer Institute.

[97]  B. Spiegelman,et al.  PPARγ: a Nuclear Regulator of Metabolism, Differentiation, and Cell Growth* , 2001, The Journal of Biological Chemistry.

[98]  A. Simopoulos,et al.  The Mediterranean diets: What is so special about the diet of Greece? The scientific evidence. , 2001, The Journal of nutrition.

[99]  R. Langenbach,et al.  Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. , 2000, Cancer research.

[100]  D. Jump The Biochemistry of n-3 Polyunsaturated Fatty Acids* 210 , 2002, The Journal of Biological Chemistry.

[101]  M. Garg,et al.  Differential effects of dietary linoleic and α-linolenic acid on lipid metabolism in rat tissues , 1988, Lipids.

[102]  Samuel Singer,et al.  Differentiation and reversal of malignant changes in colon cancer through PPARγ , 1998, Nature Medicine.

[103]  E. Emken,et al.  Dietary linoleic acid influences desaturation and acylation of deuterium-labeled linoleic and linolenic acids in young adult males. , 1994, Biochimica et biophysica acta.

[104]  H. Aburatani,et al.  Fish oil feeding alters liver gene expressions to defend against PPARalpha activation and ROS production. , 2002, American journal of physiology. Gastrointestinal and liver physiology.

[105]  Martin R. Schneider,et al.  Prostacyclin and its analogues: antimetastatic effects and mechanisms of action , 1994, Cancer and Metastasis Reviews.

[106]  J. Higdon,et al.  Supplementation of postmenopausal women with fish oil does not increase overall oxidation of LDL ex vivo compared to dietary oils rich in oleate and linoleate. , 2001, Journal of lipid research.

[107]  James B. Mitchell,et al.  The multifaceted roles of nitric oxide in cancer. , 1998, Carcinogenesis.

[108]  Maurice E. Shils,et al.  Modern Nutrition in Health and Disease , 1965, Diabetes.

[109]  E. Rimm,et al.  Intake of fat, meat, and fiber in relation to risk of colon cancer in men. , 1994, Cancer research.

[110]  Thomas E Rohan,et al.  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. , 2003, The American journal of clinical nutrition.

[111]  M. Mutanen,et al.  Determination of DNA adducts of malonaldehyde in humans: effects of dietary fatty acid composition. , 1996, Carcinogenesis.

[112]  T. Tsuruo,et al.  Inhibitory effects of n-3 polyunsaturated fatty acids on sigmoid colon cancer transformants , 1998, Journal of Gastroenterology.

[113]  P. Grimaldi Fatty acid regulation of gene expression , 2001, Current opinion in clinical nutrition and metabolic care.

[114]  J. Kinsella,et al.  Dietary arachidonate enhances tissue arachidonate levels and eicosanoid production in Syrian hamsters. , 1993, The Journal of nutrition.

[115]  S. Bulun,et al.  Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. , 1997, The Journal of clinical endocrinology and metabolism.

[116]  D. Rose,et al.  Regulation of Tumor Angiogenesis by Dietary Fatty Acids and Eicosanoids , 2000, Nutrition and cancer.

[117]  W. Willett,et al.  N-acetyl transferase 2 genotypes, meat intake and breast cancer risk. , 1999, International journal of cancer.

[118]  V. Chajès,et al.  Influence of n-3 fatty acids on the growth of human breast cancer cellsin vitro: Relationship to peroxides and Vitamin-E , 1995, Breast Cancer Research and Treatment.

[119]  E. Mantzioris,et al.  The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. , 1996, The American journal of clinical nutrition.

[120]  S. Franceschi,et al.  Diet and risk of breast cancer: major findings from an Italian case-control study. , 1998, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[121]  P. Lala,et al.  Role of nitric oxide in tumour progression with special reference to a murine breast cancer model. , 2002, Canadian journal of physiology and pharmacology.

[122]  B. Spiegelman,et al.  Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[123]  S. Clarke,et al.  Omega-3 polyunsaturated fatty acid regulation of gene expression. , 2000, Current opinion in lipidology.

[124]  R. Severson,et al.  A prospective study of demographics, diet, and prostate cancer among men of Japanese ancestry in Hawaii. , 1989, Cancer research.

[125]  J. Lupton,et al.  n-6 and n-3 polyunsaturated fatty acids differentially modulate oncogenic Ras activation in colonocytes. , 2001, American journal of physiology. Cell physiology.

[126]  W. Harris,et al.  n-3 fatty acids and serum lipoproteins: human studies. , 1997, The American journal of clinical nutrition.

[127]  P K Lala,et al.  Role of nitric oxide in carcinogenesis and tumour progression. , 2001, The Lancet. Oncology.

[128]  P. van Bladeren,et al.  The role of cyclooxygenase in n-6 and n-3 polyunsaturated fatty acid mediated effects on cell proliferation, PGE(2) synthesis and cytotoxicity in human colorectal carcinoma cell lines. , 2003, Carcinogenesis.

[129]  A. Bonanome,et al.  n-3 fatty acids do not enhance LDL susceptibility to oxidation in hypertriacylglycerolemic hemodialyzed subjects. , 1996, The American journal of clinical nutrition.

[130]  D. Jeyarajah,et al.  Docosahexaenoic acid, a component of fish oil, inhibits nitric oxide production in vitro. , 1999, The Journal of surgical research.

[131]  M. C. Archer,et al.  Effect of hormonal status on the expression of the cyclooxygenase 1 and 2 genes and prostaglandin synthesis in rat mammary glands. , 1998, Prostaglandins & other lipid mediators.

[132]  M. Lipkin,et al.  Dietary factors in human colorectal cancer. , 1999, Annual review of nutrition.

[133]  R. Schild,et al.  The activity of PPAR gamma in primary human trophoblasts is enhanced by oxidized lipids. , 2002, The Journal of clinical endocrinology and metabolism.

[134]  Bandaru S. Reddy,et al.  Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. , 1997, Cancer research.

[135]  T. Tsuchiya,et al.  Effects of Prostaglandins on Spontaneous Apoptosis in Gastric Mucosal Cells , 2004, Digestive Diseases and Sciences.

[136]  E Riboli,et al.  Fatty‐acid composition in serum phospholipids and risk of breast cancer: An incident case‐control study in Sweden , 1999, International journal of cancer.

[137]  J. Lupton,et al.  Dietary fish oil blocks carcinogen-induced down-regulation of colonic protein kinase C isozymes. , 1997, Carcinogenesis.

[138]  N. Narayanan,et al.  Docosahexaenoic acid regulated genes and transcription factors inducing apoptosis in human colon cancer cells. , 2001, International journal of oncology.

[139]  A. Wolk,et al.  Fatty fish consumption lowers the risk of endometrial cancer: a nationwide case-control study in Sweden. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[140]  A. Hernandez,et al.  The role of NF-kappaB/IkappaB proteins in cancer: implications for novel treatment strategies. , 1999, Surgical oncology.

[141]  L. Marshall,et al.  Modulation of tissue prostaglandin synthesizing capacity by increased ratios of dietary alpha-linolenic acid to linoleic acid , 1982, Lipids.

[142]  E. Schiffrin,et al.  Docosahexaenoic Acid, a Peroxisome Proliferator–Activated Receptor-&agr; Ligand, Induces Apoptosis in Vascular Smooth Muscle Cells by Stimulation of p38 Mitogen-Activated Protein Kinase , 2000, Hypertension.

[143]  A. A. Spector,et al.  Role of Plant-Derived Omega–3 Fatty Acids in Human Nutrition , 2000, Annals of Nutrition and Metabolism.

[144]  Sam W. Lee,et al.  Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: mediation through cyclooxygenase-independent pathways. , 2019, Cancer research.

[145]  B. Halliwell,et al.  Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. , 1996, The Biochemical journal.

[146]  D. Rose,et al.  Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. , 1991, Journal of the National Cancer Institute.

[147]  B. Reddy,et al.  Inhibition by dietary menhaden oil of cyclooxygenase-1 and -2 in N-nitrosomethylurea-induced rat mammary tumors. , 1999, International journal of oncology.

[148]  J. Vamecq,et al.  Medical significance of peroxisome proliferator-activated receptors , 1999, The Lancet.

[149]  D. Rose,et al.  Omega-3 fatty acids as cancer chemopreventive agents. , 1999, Pharmacology & therapeutics.

[150]  J. Gustafsson,et al.  Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[151]  Dhyan Chandra,et al.  Evidence That Arachidonate 15-Lipoxygenase 2 Is a Negative Cell Cycle Regulator in Normal Prostate Epithelial Cells* 210 , 2002, The Journal of Biological Chemistry.

[152]  C. Harris,et al.  Interactive effects of nitric oxide and the p 53 tumor suppressor gene in carcinogenesis and tumor progression , 2004 .

[153]  B. Stoll Review article n -3 Fatty acids and lipid peroxidation in breast cancer inhibition , 2002 .

[154]  L. Vatten,et al.  Frequency of meat and fish intake and risk of breast cancer in a prospective study of 14,500 norwegian women , 1990, International journal of cancer.

[155]  C. la Vecchia,et al.  Influence of food groups and food diversity on breast cancer risk in Italy , 1995, International journal of cancer.

[156]  I. Shureiqi,et al.  Decreased 13-S-hydroxyoctadecadienoic acid levels and 15-lipoxygenase-1 expression in human colon cancers. , 1999, Carcinogenesis.

[157]  V. Hubbard,et al.  Changing dietary patterns. , 1990, The American journal of clinical nutrition.

[158]  J. Auwerx,et al.  PPAR(gamma) and glucose homeostasis. , 2003, Annual review of nutrition.

[159]  P. Bougnoux,et al.  n-3 polyunsaturated fatty acids and cancer. , 1999, Current opinion in clinical nutrition and metabolic care.

[160]  E. Christiansen,et al.  Effect of dietary n-3 and n-6 fatty acids on fatty acid desaturation in rat liver. , 1991, Biochimica et biophysica acta.

[161]  S. Dahlén,et al.  Enhancement of acute allergic inflammation by indomethacin is reversed by prostaglandin E2: apparent correlation with in vivo modulation of mediator release. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[162]  S. Hamilton,et al.  Ornithine decarboxylase and polyamines in familial adenomatous polyposis. , 1997, Cancer research.

[163]  S. Sakuma,et al.  15-Hydroperoxyeicosapentaenoic acid inhibits arachidonic acid metabolism in rabbit platelets more potently than eicosapentaenoic acid. , 1996, Biochimica et biophysica acta.

[164]  B. Reddy,et al.  Dietary fish oil inhibits the expression of farnesyl protein transferase and colon tumor development in rodents. , 1998, Carcinogenesis.

[165]  J. Connolly,et al.  Antiangiogenicity of docosahexaenoic acid and its role in the suppression of breast cancer cell growth in nude mice. , 1999, International journal of oncology.

[166]  R. DuBois,et al.  The role of cyclooxygenases in inflammation, cancer, and development , 1999, Oncogene.

[167]  T. Sugimura,et al.  Nutrition and dietary carcinogens. , 2000, Carcinogenesis.

[168]  K. Houseknecht,et al.  Peroxisome proliferator-activated receptor gamma (PPARγ) and its ligands: A review , 2002 .

[169]  C. Rao,et al.  Modulating effect of amount and types of dietary fat on ornithine decarboxylase, tyrosine protein kinase and prostaglandins production during colon carcinogenesis in male F344 rats. , 1993, Carcinogenesis.

[170]  N. Tajima,et al.  Influence of highly purified eicosapentaenoic acid ethyl ester on insulin resistance in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous non-insulin-dependent diabetes mellitus. , 1997, Metabolism: clinical and experimental.

[171]  A. El-Sohemy,et al.  Regulation of mevalonate synthesis in rat mammary glands by dietary n-3 and n-6 polyunsaturated fatty acids. , 1997, Cancer research.

[172]  A. Wolk,et al.  Fatty fish consumption and risk of prostate cancer , 2001, The Lancet.

[173]  K. Houseknecht,et al.  Peroxisome proliferator-activated receptor gamma (PPARgamma) and its ligands: a review. , 2002, Domestic animal endocrinology.