Fish Oil Supplementation Inhibits NNK-Induced Lung Carcinogenesis in the A/J Mouse

High intake of fish oil with a low omega-6 (n-6)/omega-3 (n-3) polyunsaturated fatty acid (PUFA) ratio has been suggested to protect against many chronic diseases. However, the effect of different ratios of dietary n-6 and n-3 PUFA on lung tumorigenesis has not been investigated. In this study, we examined the effect of a 4 mo dietary supplementation with corn oil (with a high n-6/n-3 ratio) and fish oil (with a low n-6/n-3 ratio) as compared with soybean oil (isocaloric control with the same n-6/n-3 ratio as the base diet) on tumor incidence and tumor prevalence in the A/J mouse model of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis. We found that dietary supplementation had no effect on overall lung tumor incidence, but fish oil supplementation was able to decrease lung tumor prevalence by 78% and 80% compared to groups receiving soybean oil and corn oil supplementation, respectively. The inhibitory effect of fish oil on lung tumor prevalence was associated with increased expressions of cell cycle inhibitor p21Cip1 and lipoxygenase isoform 15-LOX in the lungs. These data suggest that fish oil with a low ratio of n-6/n-3 PUFA could be beneficial in the prevention of lung carcinogenesis.

[1]  J. Lupton,et al.  Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet. , 2008, Carcinogenesis.

[2]  W. Willett,et al.  A 22-year Prospective Study of Fish, n-3 Fatty Acid Intake, and Colorectal Cancer Risk in Men , 2008, Cancer Epidemiology Biomarkers & Prevention.

[3]  Y. Piao,et al.  Platelet-type 12-lipoxygenase accelerates tumor promotion of mouse epidermal cells through enhancement of cloning efficiency. , 2008, Carcinogenesis.

[4]  P. van’t Veer,et al.  Fish consumption, n-3 fatty acids, and colorectal cancer: a meta-analysis of prospective cohort studies. , 2007, American journal of epidemiology.

[5]  H. Friess,et al.  15-lipoxygenase-1 production is lost in pancreatic cancer and overexpression of the gene inhibits tumor cell growth. , 2007, Neoplasia.

[6]  R. Russell,et al.  Apo-10'-lycopenoic acid inhibits lung cancer cell growth in vitro, and suppresses lung tumorigenesis in the A/J mouse model in vivo. , 2007, Carcinogenesis.

[7]  B. Lai,et al.  Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate , 2007, BMC Cancer.

[8]  R. Russell,et al.  Inhibition of lung carcinogenesis by 1α,25‐dihydroxyvitamin D3 and 9‐cis retinoic acid in the A/J mouse model: Evidence of retinoid mitigation of vitamin D toxicity , 2007, International journal of cancer.

[9]  A. Zhu,et al.  9-cis-Retinoic acid inhibition of lung carcinogenesis in the A/J mouse model is accompanied by increased expression of RAR-beta but no change in cyclooxygenase-2. , 2006, Cancer letters.

[10]  A. Habenicht,et al.  What are cyclooxygenases and lipoxygenases doing in the driver's seat of carcinogenesis? , 2006, International journal of cancer.

[11]  Chengwei He,et al.  Melanoma growth is reduced in fat-1 transgenic mice: Impact of omega-6/omega-3 essential fatty acids , 2006, Proceedings of the National Academy of Sciences.

[12]  R. Burger,et al.  Use of a dummy (pacifier) during sleep and risk of sudden infant death syndrome (SIDS): population based case-control study , 2005, BMJ : British Medical Journal.

[13]  Jeffrey S. Morris,et al.  The critical role of 15-lipoxygenase-1 in colorectal epithelial cell terminal differentiation and tumorigenesis. , 2005, Cancer research.

[14]  S. Baek,et al.  Overexpression of 15-Lipoxygenase-1 Induces Growth Arrest through Phosphorylation of p53 in Human Colorectal Cancer Cells , 2005, Molecular Cancer Research.

[15]  J. Kang,et al.  Decreased n-6/n-3 fatty acid ratio reduces the invasive potential of human lung cancer cells by downregulation of cell adhesion/invasion-related genes. , 2005, Carcinogenesis.

[16]  Maurice Bennink,et al.  Docosahexaenoic acid attenuates mycotoxin-induced immunoglobulin a nephropathy, interleukin-6 transcription, and mitogen-activated protein kinase phosphorylation in mice. , 2004, The Journal of nutrition.

[17]  Magnus Ingelman-Sundberg,et al.  Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. , 2004, The American journal of clinical nutrition.

[18]  P. Astorg.  Dietary n – 6 and n – 3 Polyunsaturated Fatty Acids and Prostate Cancer Risk: A Review of Epidemiological and Experimental Evidence , 2004, Cancer Causes & Control.

[19]  Claude Pichard,et al.  n-3 polyunsaturated fatty acids and colon cancer prevention. , 2004, Clinical nutrition.

[20]  G. Burdge.  Alpha-linolenic acid metabolism in men and women: nutritional and biological implications. , 2004, Current opinion in clinical nutrition and metabolic care.

[21]  D. Hwang,et al.  Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids. , 2003, Journal of lipid research.

[22]  M. Inoue,et al.  Diet and Lung Cancer Risk From a 14-Year Population-Based Prospective Study in Japan: With Special Reference to Fish Consumption , 2003, Nutrition and cancer.

[23]  B. Wong,et al.  15-Lipoxygenase-1 mediates cyclooxygenase-2 inhibitor-induced apoptosis in gastric cancer. , 2003, Carcinogenesis.

[24]  H. Wada,et al.  Clinical significance of p21 expression in non-small-cell lung cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

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

[26]  D. Jump,et al.  Dietary polyunsaturated fatty acids and regulation of gene transcription , 2002, Current opinion in lipidology.

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

[28]  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.

[29]  M. Ando,et al.  Dietary Habits and Risk of Lung Cancer Death in a Large‐scale Cohort Study (JACC Study) in Japan by Sex and Smoking Habit , 2001, Japanese journal of cancer research : Gann.

[30]  B. Wong,et al.  12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells. , 2001, Carcinogenesis.

[31]  S. Lippman,et al.  15-Lipoxygenase-1 mediates nonsteroidal anti-inflammatory drug-induced apoptosis independently of cyclooxygenase-2 in colon cancer cells. , 2000, Cancer research.

[32]  H. Kesteloot,et al.  Fish consumption is inversely associated with male lung cancer mortality in countries with high levels of cigarette smoking or animal fat consumption. , 2000, International journal of epidemiology.

[33]  I. Cameron,et al.  Dietary fish oil sensitizes A549 lung xenografts to doxorubicin chemotherapy. , 2000, Cancer letters.

[34]  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.

[35]  P. Laake,et al.  Dietary fat intake and risk of lung cancer: a prospective study of 51,452 Norwegian men and women. , 1997, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[36]  W. Willett,et al.  Specific fatty acids and risks of breast and prostate cancer: dietary intake. , 1997, The American journal of clinical nutrition.

[37]  M. Shinitzky,et al.  Dietary fish oil suppresses tumor growth and metastasis of Lewis lung carcinoma in mice , 1997 .

[38]  S. Wilczynski,et al.  Increased 12-lipoxygenase expression in breast cancer tissues and cells. Regulation by epidermal growth factor. , 1997, The Journal of clinical endocrinology and metabolism.

[39]  A. Castonguay,et al.  Inhibition of lung tumourigenesis by sulindac: comparison of two experimental protocols. , 1997, Carcinogenesis.

[40]  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.

[41]  D. Grignon,et al.  Elevated 12-lipoxygenase mRNA expression correlates with advanced stage and poor differentiation of human prostate cancer. , 1995, Urology.

[42]  E. Wynder,et al.  A study of tobacco carcinogenesis: effect of the fat content of the diet on the carcinogenic activity of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in F344 rats. , 1993, Cancer research.

[43]  C. Quintans,et al.  Effects of an eicosapentaenoic and docosahexaenoic acid concentrate on a human lung carcinoma grown in nude mice , 1991, Lipids.

[44]  A. Simopoulos.  Omega-3 fatty acids in health and disease and in growth and development. , 1991, The American journal of clinical nutrition.

[45]  S. Amin,et al.  Rapid single-dose model for lung tumor induction in A/J mice by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and the effect of diet. , 1989, Carcinogenesis.

[46]  J. Gart,et al.  Dietary habits and lung cancer risk , 1983, International journal of cancer.

[47]  C. Ruxton,et al.  The health benefits of omega-3 polyunsaturated fatty acids: a review of the evidence. , 2007, Journal of human nutrition and dietetics : the official journal of the British Dietetic Association.

[48]  M. Sopori,et al.  Early manifestations of NNK-induced lung cancer: role of lung immunity in tumor susceptibility. , 2007, American journal of respiratory cell and molecular biology.

[49]  P. Champéroux,et al.  Dietary long-chain omega-3 fatty acids of marine origin: a comparison of their protective effects on coronary heart disease and breast cancers. , 2006, Progress in biophysics and molecular biology.

[50]  V. Chajès,et al.  Omega-6/omega-3 polyunsaturated fatty acids ratio and breast cancer. , 2005, World review of nutrition and dietetics.

[51]  T. Eling,et al.  15-Lipoxygenase-1 has anti-tumorigenic effects in colorectal cancer. , 2004, Prostaglandins, leukotrienes, and essential fatty acids.

[52]  M. Shinitzky,et al.  Suppression of tumor growth and metastasis by dietary fish oil combined with vitamins E and C and cisplatin , 2001, Cancer Chemotherapy and Pharmacology.

[53]  H. Kung,et al.  Inhibition of 12-lipoxygenase induced apoptosis in human gastric cancer cells , 2000 .

[54]  R. Grimble.  Nutritional influences on inflammation. , 1999, Nestle Nutrition workshop series. Clinical & performance programme.

[55]  E. Wynder,et al.  Increased expression of cyclooxygenase-2 in rat lung tumors induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanone: the impact of a high-fat diet. , 1999, Cancer research.

[56]  R. Grimble,et al.  Modulation of pro-inflammatory cytokine biology by unsaturated fatty acids. , 1998, Zeitschrift fur Ernahrungswissenschaft.

[57]  L. Watson,et al.  Dietary and alcohol intake, smoking pattern, occupational risk, and family history in lung cancer patients: results of a case-control study in males. , 1989, Nutrition and cancer.

[58]  L. Koo.  Dietary habits and lung cancer risk among Chinese females in Hong Kong who never smoked. , 1988, Nutrition and cancer.

[59]  G. Stoner,et al.  Lung tumors in mice: application to carcinogenesis bioassay. , 1975, Advances in cancer research.