Açaí Berries Inhibit Colon Tumorigenesis in Azoxymethane/Dextran Sulfate Sodium-Treated Mice
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Background/Aims: The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/ dextran sulfate sodium (DSS)-induced colorectal cancer development. Methods: The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. Results: Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. Conclusions: Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer.
Abstract
Background/Aims: The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/ dextran sulfate sodium (DSS)-induced colorectal cancer development. Methods: The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. Results: Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. Conclusions: Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer.
참고문헌 (39)
- Ferlay J, "Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008", Int J Cancer, 127, pp.2893~2917 (2010)
- Kuper H, "Infections as a major preventable cause of human cancer", J Intern Med, 248, pp.171~183 (2000)
- Mantovani A, "Cancer-related inflammation", Nature, 454, pp.436~444 (2008)
- Feagins LA, "Carcinogenesis in IBD: potential targets for the prevention of colorectal cancer", Nat Rev Gastroenterol Hepatol, 6, pp.297~305 (2009)
- Lakatos PL, "Once daily 5-aminosalicylic acid for the treatment of ulcerative colitis: are we there yet", Pharmacol Res, 58, pp.190~195 (2008)
- Meira LB, "DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice", J Clin Invest, 118, pp.2516~2525 (2008)
- Grivennikov SI, "Inflammation and colorectal cancer: colitis-associated neoplasia", Semin Immunopathol, 35, pp.229~244 (2013)
- Becker C, "TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 transsignaling", Immunity, 21, pp.491~501 (2004)
- Popivanova BK, "Blocking TNF-alpha in mice reduces colorectal carcinogenesis associated with chronic colitis", J Clin Invest, 118, pp.560~570 (2008)
- Bollrath J, "gp130-mediated Stat3activation in enterocytes regulates cell survival and cell-cycle progression during colitis-associated tumorigenesis", Cancer Cell, 15, pp.91~102 (2009)
- Grivennikov S, "IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitisassociated cancer", Cancer Cell, 15, pp.103~113 (2009)
- Half E, "Colon cancer: preventive agents and the present status of chemoprevention", Expert Opin Pharmacother, 10, pp.211~219 (2009)
- Das D, "Chemoprevention of colorectal cancer", Digestion, 76, pp.51~67 (2007)
- Poulose SM, "Anthocyanin-rich açai (Euterpe oleracea Mart.) fruit pulp fractions attenuate inflammatory stress signaling in mouse brain BV-2 microglial cells", J Agric Food Chem, 60, pp.1084~1093 (2012)
- Xie C, "Açaí juice attenuates atherosclerosis in ApoE deficient mice through antioxidant and anti-inflammatory activities", Atherosclerosis, 216, pp.327~333 (2011)
- Moura RS, "Effects of Euterpe oleracea Mart. (AÇAÍ) extract in acute lung inflammation induced by cigarette smoke in the mouse", Phytomedicine, 19, pp.262~269 (2012)
- Del Pozo-Insfran D, "Açai (Euterpe oleracea Mart.) polyphenolics in their glycoside and aglycone forms induce apoptosis of HL-60 leukemia cells", J Agric Food Chem, 54, pp.1222~1229 (2006)
- Dias MM, "Pro-apoptotic activities of polyphenolics from açai (Euterpe oleracea Martius) in human SW-480 colon cancer cells", Nutr Cancer, 66, pp.1394~1405 (2014)
- Fragoso MF, "Açai (Euterpe oleracea Mart.) feeding attenuates dimethylhydrazine-induced rat colon carcinogenesis", Food Chem Toxicol, 58, pp.68~76 (2013)
- Stoner GD, "Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats", Pharm Res, 27, pp.1138~1145 (2010)
- National Research Council (US) Subcommittee on Laboratory Animal Nutrition, "Nutrient requirements of laboratory animals" (1995), National Academy Press
- Yum HW, "Oligonol inhibits dextran sulfate sodium-induced colitis and colonic adenoma formation in mice", Antioxid Redox Signal, 19, pp.102~114 (2013)
- Hamilton SR, "World Health Organization classification of tumors: pathology and genetics of tumours of the digestive system" (2000), IARC Press
- Surh YJ, "Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals:down-regulation of COX-2 and iNOS through suppression of NF-kappa B activatio", Mutat Res, 480-481, pp.243~268 (2001)
- Kubben FJ, "Proliferating cell nuclear antigen (PCNA): a new marker to study human colonic cell proliferation", Gut, 35, pp.530~535 (1994)
- Mertens-Talcott SU, "Pharmacokinetics of anthocyanins and antioxidant effects after the consumption of anthocyanin-rich acai juice and pulp (Euterpe oleracea Mart.) in human healthy volunteers", J Agric Food Chem, 56, pp.7796~7802 (2008)
- Tessner TG, "Prostaglandin E2 reduces radiation-induced epithelial apoptosis through a mechanism involving AKT activation and bax translocation", J Clin Invest, 114, pp.1676~1685 (2004)
- Pozzi A, "Colon carcinoma cell growth is associated with prostaglandin E2", EP4 receptor-evoked ERK activation, 2004, pp.279, 29797~29804
- Federico A, "Chronic inflammation and oxidative stress in human carcinogenesis", Int J Cancer, 121, pp.2381~2386 (2007)
- Lee IA, "Dextran sulfate sodium and 2,4,6-trinitrobenzene sulfonic acid induce lipid peroxidation by the proliferation of intestinal gram-negative bacteria in mice", J Inflamm (Lond), 7, pp.7~ (2010)
- Schumacker PT, "Reactive oxygen species in cancer cells: live by the sword, die by the sword", Cancer Cell, 10, pp.175~176 (2006)
- Petros JA, "mtDNA mutations increase tumorigenicity in prostate cancer", Proc Natl Acad Sci U S A, 102, pp.719~724 (2005)
- Gupta SC, "Upsides and downsides of reactive oxygen species for cancer: the roles of reactive oxygen species in tumorigenesis, prevention, and therapy", Antioxid Redox Signal, 16, pp.1295~1322 (2012)
- Watson AJ, "Apoptosis and colorectal cancer", Gut, 53, pp.1701~1709 (2004)
- Kim WK, "Quercetin decreases the expression", J Nutr Biochem, 16, pp.155~162 (2005)
- Athar M, "Multiple molecular targets of resveratrol: anti-carcinogenic mechanisms", Arch Biochem Biophys, 486, pp.95~102 (2009)
- Ramos S, "Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways", Mol Nutr Food Res, 52, pp.507~526 (2008)
- Noratto GD, "The drug resistance suppression induced by curcuminoids in colon cancer SW-480 cells is mediated by reactive oxygen species-induced disruption of the microRNA-27a-ZBTB10-Sp axis", Mol Nutr Food Res, 57, pp.1638~1648 (2013)
- Jensen GS, "In vitro and in vivo antioxidant and anti-inflammatory capacities of an antioxidantrich fruit and berry juice blend: results of a pilot and randomized, double-blinded, placebo-controlled, crossover study", J Agric Food Chem, 56, pp.8326~8333 (2008)
