Lipids in Health and Disease | |
Anti-inflammatory effects of fish oil in ovaries of laying hens target prostaglandin pathways | |
Dale Buchanan Hales1  Nawneet K Kurrey1  Stacey R McGee1  Carolynn C Small1  Erfan Eilati1  | |
[1] Department of Physiology, Southern Illinois University Carbondale, School of Medicine, Life Science II, Room 250 (M/C 6512), 1125 Lincoln Drive, Carbondale, IL 62901, USA | |
关键词: Prostaglandin E2; Cyclooxygenase; Inflammation; Omega-3 fatty acids; Laying hen; Fish oil; | |
Others : 829502 DOI : 10.1186/1476-511X-12-152 |
|
received in 2013-09-03, accepted in 2013-10-18, 发布年份 2013 | |
【 摘 要 】
Background
An effective way to control cancer is by prevention. Ovarian cancer is the most lethal gynecological malignancy. Progress in the treatment and prevention of ovarian cancer has been hampered due to the lack of an appropriate animal model and absence of effective chemo-prevention strategies. The domestic hens spontaneously develop ovarian adenocarcinomas that share similar histological appearance and symptoms such as ascites and metastasis with humans. There is a link between chronic inflammation and cancer. Prostaglandin E2 (PGE2) is the most pro-inflammatory ecoisanoid and one of the downstream products of two isoforms of cyclooxygenase (COX) enzymes: COX-1 and COX-2. PGE2 exerts its effects on target cells by coupling to four subtypes of receptors which have been classified as EP1-4. Fish oil is a source of omega-3 fatty acids (OM-3FAs) which may be effective in prevention of ovarian cancer. Our objective was to assess the potential impact of fish oil on expression of COX enzymes, PGE2 concentration, apoptosis and proliferation in ovaries of laying hens.
Methods
48 white Leghorn hens were fed 50, 100, 175, 375 and 700 mg/kg fish oil for 21 days. The OM3-FAs and omega-6 fatty acids contents of egg yolks were determined by Gas Chromatography. Proliferation, apoptosis, COX-1, COX-2 and prostaglandin receptor subtype 4 (EP4) protein and mRNA expression and PGE2 concentration in ovaries were measured by PCNA, TUNEL, Western blot, quantitative real-time qPCR and ELISA, respectively.
Results
Consumption of fish oil increased the incorporation of OM-3FAs into yolks and decreased both COX-1 and COX-2 protein and mRNA expression. In correlation with COXs down-regulation, fish oil significantly reduced the concentrations of PGE2 in ovaries. EP4 protein and mRNA expression in ovaries of hens was not affected by fish oil treatment. A lower dose of fish oil increased the egg laying frequency. 175 and 700 mg/kg fish oil reduced proliferation and 700 mg/kg increased apoptosis in hen ovaries.
Conclusions
Our findings suggest that the lower doses of fish oil reduce inflammatory PG and may be an effective approach in preventing ovarian carcinogenesis. These findings may provide the basis for clinical trials utilizing fish oil as a dietary intervention targeting prostaglandin biosynthesis for the prevention and treatment of ovarian cancer.
【 授权许可】
2013 Eilati et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140714071333746.pdf | 2356KB | download | |
Figure 5. | 90KB | Image | download |
Figure 4. | 47KB | Image | download |
Figure 3. | 52KB | Image | download |
Figure 2. | 59KB | Image | download |
Figure 1. | 85KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
【 参考文献 】
- [1]Williams CS, Mann M, DuBois RN: The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 1999, 18(55):7908-7916.
- [2]Gupta RA, Tejada LV, Tong BJ, Das SK, Morrow JD, Dey SK, DuBois RN: Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer. Cancer Res 2003, 63(5):906-911.
- [3]Daikoku T, Wang D, Tranguch S, Morrow JD, Orsulic S, DuBois RN, Dey SK: Cyclooxygenase-1 Is a Potential Target for Prevention and Treatment of Ovarian Epithelial Cancer. Cancer Res 2005, 65(9):3735-3744.
- [4]Smith WL: Cyclooxygenases, peroxide tone and the allure of fish oil. Curr Opin Cell Biol 2005, 17(2):174-182.
- [5]Denkert C, Kobel M, Pest S, Koch I, Berger S, Schwabe M, Siegert A, Reles A, Klosterhalfen B, Hauptmann S: Expression of cyclooxygenase 2 is an independent prognostic factor in human ovarian carcinoma. Am J Pathol 2002, 160(3):893-903.
- [6]Urick ME, Johnson PA: Cyclooxygenase 1 and 2 mRNA and protein expression in the Gallus domesticus model of ovarian cancer. Gynecol Oncol 2006, 103(2):673-678.
- [7]Hales DB, Zhuge Y, Lagman JA, Ansenberger K, Mahon C, Barua A, Luborsky JL, Bahr JM: Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus domesticus). Endocrine 2008, 33(3):235-244.
- [8]Reese J, Zhao X, Ma WG, Brown N, Maziasz TJ, Dey SK: Comparative analysis of pharmacologic and/or genetic disruption of cyclooxygenase-1 and cyclooxygenase-2 function in female reproduction in mice. Endocrinology 2001, 142(7):3198-3206.
- [9]Greene ER, Huang S, Serhan CN, Panigrahy D: Regulation of inflammation in cancer by eicosanoids. Prostaglandins Other Lipid Mediat 2011, 96(1–4):27-36.
- [10]Gupta RA, Dubois RN: Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer 2001, 1(1):11-21.
- [11]Terada N, Shimizu Y, Kamba T, Inoue T, Maeno A, Kobayashi T, Nakamura E, Kamoto T, Kanaji T, Maruyama T, et al.: Identification of EP4 as a potential target for the treatment of castration-resistant prostate cancer using a novel xenograft model. Cancer Res 2010, 70(4):1606-1615.
- [12]Chell SD, Witherden IR, Dobson RR, Moorghen M, Herman AA, Qualtrough D, Williams AC, Paraskeva C: Increased EP4 receptor expression in colorectal cancer progression promotes cell growth and anchorage independence. Cancer Res 2006, 66(6):3106-3113.
- [13]Ma X, Kundu N, Rifat S, Walser T, Fulton AM: Prostaglandin E receptor EP4 antagonism inhibits breast cancer metastasis. Cancer Res 2006, 66(6):2923-2927.
- [14]Ansenberger K, Zhuge Y, Richards C, Barua A, Luborsky JL, Bahr JM, Hales DB: Decreased severity of ovarian cancer and increased survival in hens fed a flaxseed enriched diet for one year. Gynecol Oncol 2010, 117:341-347.
- [15]Glade MJ: Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition 1999, 15(6):523-526.
- [16]Sharma A, Belna J, Espat J, Rodriguez G, Cannon VT, Hurteau JA: Effects of omega-3 fatty acids on components of the transforming growth factor beta-1 pathway: implication for dietary modification and prevention in ovarian cancer. Am J Obstet Gynecol 2009, 200(5):e511-516.
- [17]Simopoulos AP: Omega-3 fatty acids in health and disease and in growth and development. Am J Clin Nutr 1991, 54(3):438-463.
- [18]Calviello G, Serini S, Piccioni E: n-3 polyunsaturated fatty acids and the prevention of colorectal cancer: molecular mechanisms involved. Curr Med Chem 2007, 14(29):3059-3069.
- [19]Ansenberger K, Zhuge Y, Lagman JA, Richards C, Barua A, Bahr JM, Hales DB: E-cadherin expression in ovarian cancer in the laying hen, Gallus domesticus, compared to human ovarian cancer. Gynecol Oncol 2009, 113(3):362-369.
- [20]Hales DB, Zhuge Y, Lagman JAJ, Ansenberger K, Mahon C, Narua A, Luborsky J, Bahr JM: Cyclooxygenases expression and distribution in the normal ovary and their role in ovarian cancer in the domestic hen (Gallus Domesticus). Endocrine 2008. in press
- [21]Zhuge Y, Lagman JA, Ansenberger K, Mahon CJ, Daikoku T, Dey SK, Bahr JM, Hales DB: CYP1B1 expression in ovarian cancer in the laying hen Gallusdomesticus. Gynecologic oncology 2009, 112(1):171-178.
- [22]Rodriguez-Burford C, Barnes MN, Berry W, Partridge EE, Grizzle WE: Immunohistochemical expression of molecular markers in an avian model: a potential model for preclinical evaluation of agents for ovarian cancer chemoprevention. Gynecol Oncol 2001, 81(3):373-379.
- [23]Barua A, Bitterman P, Abramowicz JS, Dirks AL, Bahr JM, Hales DB, Bradaric MJ, Edassery SL, Rotmensch J, Luborsky JL: Histopathology of ovarian tumors in laying hens: a preclinical model of human ovarian cancer. Int J Gynecol Cancer 2009, 19(4):531-539.
- [24]Eilati E, Pan L, Bahr JM, Hales DB: Age dependent increase in prostaglandin pathway coincides with onset of ovarian cancer in laying hens. Prostaglandins Leukot Essent Fatty Acids 2012, 87(6):177-184.
- [25]Eilati E, Bahr JM, Hales DB: Long term consumption of flaxseed enriched diet decreased ovarian cancer incidence and prostaglandin E in hens. Gynecol Oncol 2013. DOI:10.1016/j.ygyno.2013.05.018
- [26]Trebunova A, Vasko L, Svedova M, Kastel R, Tuckova M, Mach P: The influence of omega-3 polyunsaturated fatty acids feeding on composition of fatty acids in fatty tissues and eggs of laying hens. Dtsch Tierarztl Wochenschr 2007, 114(7):275-279.
- [27]Bautista-Ortega J, Goeger DE, Cherian G: Egg yolk omega-6 and omega-3 fatty acids modify tissue lipid components, antioxidant status, and ex vivo eicosanoid production in chick cardiac tissue. Poult Sci 2009, 88(6):1167-1175.
- [28]Jump DB: The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 2002, 277(11):8755-8758.
- [29]Schreiner M, Hulan HW, Razzazi-Fazeli E, Bohm J, Iben C: Feeding laying hens seal blubber oil: effects on egg yolk incorporation, stereospecific distribution of omega-3 fatty acids, and sensory aspects. Poult Sci 2004, 83(3):462-473.
- [30]Broughton KS, Bayes J, Culver B: High alpha-linolenic acid and fish oil ingestion promotes ovulation to the same extent in rats. Nutr Res 2010, 30(10):731-738.
- [31]Ebeid T, Eid Y, Saleh A, Abd El-Hamid H: Ovarian follicular development, lipid peroxidation, antioxidative status and immune response in laying hens fed fish oil-supplemented diets to produce n-3-enriched eggs. Animal 2008, 2(1):84-91.
- [32]Meluzzi A, Sirri F, Manfreda G, Tallarico N, Franchini A: Effects of dietary vitamin E on the quality of table eggs enriched with n-3 long-chain fatty acids. Poult Sci 2000, 79(4):539-545.
- [33]Simopoulos AP: Human requirement for N-3 polyunsaturated fatty acids. Poult Sci 2000, 79(7):961-970.
- [34]Smith WL: Nutritionally essential fatty acids and biologically indispensable cyclooxygenases. Trends Biochem Sci 2008, 33(1):27-37.
- [35]Corey EJ, Shih C, Cashman JR: Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis. Proc Natl Acad Sci USA 1983, 80(12):3581-3584.
- [36]Kino Y, Kojima F, Kiguchi K, Igarashi R, Ishizuka B, Kawai S: Prostaglandin E2 production in ovarian cancer cell lines is regulated by cyclooxygenase-1, not cyclooxygenase-2. Prostaglandins Leukot Essent Fatty Acids 2005, 73(2):103-111.
- [37]Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A: The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer 2009, 45(12):2077-2086.
- [38]Singh J, Hamid R, Reddy BS: Dietary fat and colon cancer: modulation of cyclooxygenase-2 by types and amount of dietary fat during the postinitiation stage of colon carcinogenesis. Cancer Res 1997, 57(16):3465-3470.
- [39]Aronson WJ, Glaspy JA, Reddy ST, Reese D, Heber D, Bagga D: Modulation of omega-3/omega-6 polyunsaturated ratios with dietary fish oils in men with prostate cancer. Urology 2001, 58(2):283-288.
- [40]Massaro M, Habib A, Lubrano L, Del Turco S, Lazzerini G, Bourcier T, Weksler BB, De Caterina R: The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKC epsilon inhibition. Proc Natl Acad Sci USA 2006, 103(41):15184-15189.
- [41]Ghosh S, Karin M: Missing pieces in the NF-kappaB puzzle. Cell 2002, 109(Suppl):S81-96.
- [42]Xi S, Cohen D, Chen LH: Effects of fish oil on cytokines and immune functions of mice with murine AIDS. J Lipid Res 1998, 39(8):1677-1687.
- [43]Wang TM, Chen CJ, Lee TS, Chao HY, Wu WH, Hsieh SC, Sheu HH, Chiang AN: Docosahexaenoic acid attenuates VCAM-1 expression and NF-kappaB activation in TNF-alpha-treated human aortic endothelial cells. J Nutr Biochem 2011, 22(2):187-194.
- [44]Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JW, Cannon JG, Rogers TS, Klempner MS, Weber PC, et al.: The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989, 320(5):265-271.
- [45]Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ: 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. Am J Clin Nutr 1996, 63(1):116-122.
- [46]Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, Dinarello CA, Gorbach SL: Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 1991, 121(4):547-555.
- [47]Swails WS, Kenler AS, Driscoll DF, DeMichele SJ, Babineau TJ, Utsunamiya T, Chavali S, Forse RA, Bistrian BR: Effect of a fish oil structured lipid-based diet on prostaglandin release from mononuclear cells in cancer patients after surgery. JPEN J Parenter Enteral Nutr 1997, 21(5):266-274.
- [48]Moonen HJ, Dommels YE, van Zwam M, van Herwijnen MH, Kleinjans JC, Alink GM, de Kok TM: Effects of polyunsaturated fatty acids on prostaglandin synthesis and cyclooxygenase-mediated DNA adduct formation by heterocyclic aromatic amines in human adenocarcinoma colon cells. Molecular carcinogenesis 2004, 40(3):180-188.
- [49]Kobel M, Reuss A, Bois A, Kommoss S, Kommoss F, Gao D, Kalloger SE, Huntsman DG, Gilks CB: The biological and clinical value of p53 expression in pelvic high-grade serous carcinomas. J Pathol 2010, 222(2):191-198.
- [50]Wada M, DeLong CJ, Hong YH, Rieke CJ, Song I, Sidhu RS, Yuan C, Warnock M, Schmaier AH, Yokoyama C, et al.: Enzymes and receptors of prostaglandin pathways with arachidonic acid-derived versus eicosapentaenoic acid-derived substrates and products. J Biol Chem 2007, 282(31):22254-22266.
- [51]Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST: Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion. Proc Natl Acad Sci USA 2003, 100(4):1751-1756.
- [52]Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM: n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 2006, 83(6 Suppl):1526S-1535S.
- [53]Rodriguez-Leyva D, Dupasquier CM, McCullough R, Pierce GN: The cardiovascular effects of flaxseed and its omega-3 fatty acid, alpha-linolenic acid. Can J Cardiol 2010, 26(9):489-496.
- [54]Munkarah AR, Morris R, Baumann P, Deppe G, Malone J, Diamond MP, Saed GM: Effects of prostaglandin E(2) on proliferation and apoptosis of epithelial ovarian cancer cells. J Soc Gynecol Investig 2002, 9(3):168-173.
- [55]Kushlinskii NE, Podistov Iu I, Laktionov KP, Karseladze AI, Babkina IV, Kerimova GI: Prostaglandins E in the primary tumor, metastases, and ascitic fluid of patients with ovarian cancer. Biull Eksp Biol Med 1997, 123(1):83-86.
- [56]Eilati E, Hales K, Zhuge Y, Ansenberger Fricano K, Yu R, van Breemen RB, Hales DB: Flaxseed enriched diet-mediated reduction in ovarian cancer severity is correlated to the reduction of prostaglandin E2 in laying hen ovaries. Prostaglandins Leukot Essent Fatty Acids 2013, 89(4):179-187.
- [57]Spinella F, Rosano L, Di Castro V, Natali PG, Bagnato A: Endothelin-1-induced prostaglandin E2-EP2, EP4 signaling regulates vascular endothelial growth factor production and ovarian carcinoma cell invasion. J Biol Chem 2004, 279(45):46700-46705.
- [58]Duffy DM, McGinnis LK, Vandevoort CA, Christenson LK: Mammalian oocytes are targets for prostaglandin E2 (PGE2) action. Reprod Biol Endocrinol 2010, 8:131. BioMed Central Full Text
- [59]Manna S, Chakraborty T, Ghosh B, Chatterjee M, Panda A, Srivastava S, Rana A: Dietary fish oil associated with increased apoptosis and modulated expression of Bax and Bcl-2 during 7,12-dimethylbenz(alpha)anthracene-induced mammary carcinogenesis in rats. Prostaglandins Leukot Essent Fatty Acids 2008, 79(1–2):5-14.
- [60]Manna S, Chakraborty T, Damodaran S, Samanta K, Rana B, Chatterjee M: Protective role of fish oil (Maxepa) on early events of rat mammary carcinogenesis by modulation of DNA-protein crosslinks, cell proliferation and p53 expression. Cancer Cell Int 2007, 7:6. BioMed Central Full Text
- [61]Hong MY, Bancroft LK, Turner ND, Davidson LA, Murphy ME, Carroll RJ, Chapkin RS, Lupton JR: Fish oil decreases oxidative DNA damage by enhancing apoptosis in rat colon. Nutr Cancer 2005, 52(2):166-175.
- [62]Hong MY, Chapkin RS, Davidson LA, Turner ND, Morris JS, Carroll RJ, Lupton JR: Fish oil enhances targeted apoptosis during colon tumor initiation in part by downregulating Bcl-2. Nutr Cancer 2003, 46(1):44-51.
- [63]Wang YW, Field CJ, Sim JS: Dietary polyunsaturated fatty acids alter lymphocyte subset proportion and proliferation, serum immunoglobulin G concentration, and immune tissue development in chicks. Poult Sci 2000, 79(12):1741-1748.
- [64]Fritsche KL, Cassity NA, Huang SC: Effect of dietary fat source on antibody production and lymphocyte proliferation in chickens. Poult Sci 1991, 70(3):611-617.
- [65]Wang D, Dubois RN: Prostaglandins and cancer. Gut 2006, 55(1):115-122.