Brewers’ rice induces apoptosis in azoxymethane-induced colon carcinogenesis in rats via suppression of cell proliferation and the Wnt signaling pathway

BMC Complementary and Alternative Medicine

Roselina Karim²  Hazilawati Hamzah¹  Heshu Sulaiman Rahman¹  Norhaizan Mohd Esa³  Bee Ling Tan⁴ 

[1] Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia;Department of Food Technology, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia;Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia;Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia

关键词: Apoptosis;    Ki-67;    Beta-catenin;    Colon cancer;    Brewers’ rice;   

Others  :  1086947
DOI  :  10.1186/1472-6882-14-304

 received in 2014-05-21, accepted in 2014-08-13,  发布年份 2014

【 摘 要 】

Background

Brewers’ rice is locally known as temukut, is a byproduct of the rice milling process, and consists of broken rice, rice bran, and rice germ. Unlike rice bran, the health benefit of brewers’ rice has yet to be fully studied. Our present study aimed to identify the chemopreventive potential of brewers’ rice with colonic tumor formation and to examine further the mechanistic action of brewers’ rice during colon carcinogenesis.

Methods

Male Sprague–Dawley rats were randomly divided into five groups: (G1) normal; (G2) azoxymethane (AOM) alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers’ rice, respectively. Rats in group 2 to 5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. Colon tumor incidence and multiplicity was assessed by hematoxylin and eosin (H&E) staining. The expression of β-catenin, cyclooxygenase-2 (COX-2), and Ki-67 was evaluated by immunohistochemical staining. The apoptosis-inducing activity was analyzed using a TUNEL assay. The data were analyzed using a one-way analysis of variance (ANOVA) with P-value<0.05 was considered significant.

Results

Overall analyses revealed that brewers’ rice reduced colon tumor incidence and multiplicity. The results from immunohistochemistry analysis also showed that brewers’ rice decreased the expression of β-catenin, COX-2, and Ki-67 in a dose-dependent manner. Furthermore, TUNEL analysis demonstrated that administration of brewers’ rice in AOM-induced rat colorectal cancer resulted in a dose-dependent increase in cell apoptosis.

Conclusions

Taken together, our data suggested that brewers’ rice can inhibit cell proliferation, induce apoptosis, and suppress COX-2 and β-catenin expression via the Wnt signaling pathway and holds great promise in the field of chemoprevention as a dietary agent.

【 授权许可】

   
2014 Tan et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Cancer J Clin 2005, 55:74-108.
• [2]National Cancer Registry Malaysia: Malaysian cancer statistics-data and figure Peninsular Malaysia 2006. 2006. http://www.moh.gov.my/images/gallery/Report/Cancer/MalaysiaCancerStatistics_2006.pdf webcite
• [3]Suh Y, Afaq F, Johnson J, Mukhtar H: A plant flavonoid fisetin induces apoptosis in colon cancer cells by inhibition of COX2 and Wnt/EGFR/NF-kB-signaling pathways. Carcinogenesis 2009, 30:300-307.
• [4]Smith WL, Garavito RM, DeWitt DL: Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 1996, 271:33157-33160.
• [5]Turini ME, DuBois RN: Cyclooxygenase-2: A therapeutic target. Annu Rev Med 2002, 53:35-57.
• [6]Möbius C, Stein HJ, Spiess C, Becker I, Feith M, Theisen J, Gais P, Jütting U, Siewert JR: COX-2 expression, angiogenesis, proliferation and survival in Barrett’s cancer. Eur J Surg Oncol 2005, 31:755-759.
• [7]Kikuchi Y, Dinjens WN, Bosman FT: Proliferation and apoptosis in proliferative lesions of the colon and rectum. Virchows Arch 1997, 431:111-117.
• [8]Slavin J, Jacobs D, Marquart L: Whole-grain consumption and chronic disease: protective mechanisms. Nutr Cancer 1997, 27:14-21.
• [9]Wilson TA, Idreis HM, Taylor CM, Nicolosi RJ: Whole fat rice bran reduces the development of early aortic atherosclerosis in hypercholesterolemic hamsters compared with wheat bran. Nutr Res 2002, 22:1319-1332.
• [10]Hudson EA, Dinh PA, Kokubun T, Simmonds MS, Gescher A: Characterization of potentially chemopreventive phenols in extracts of brown rice that inhibit the growth of human breast and colon cancer cells. Cancer Epidemiol Biomarkers Prev 2000, 9:1163-1170.
• [11]Verschoyle RD, Greaves P, Cai H, Edwards RE, Steward WP, Gescher AJ: Evaluation of the cancer chemopreventive efficacy of rice bran in genetic mouse models of breast, prostate and intestinal carcinogenesis. Br J Cancer 2007, 96:248-254.
• [12]Norhaizan ME, Tan BL, Loh SP: By-products of rice processing: An overview of health benefits and applications. J Rice Res 2013, 1:107.
• [13]Tan BL, Norhaizan ME, Suhaniza HJ, Lai CC, Norazalina S, Roselina K: Antioxidant properties and antiproliferative effect of brewers’ rice extract (temukut) on selected cancer cell lines. Int Food Res J 2013, 20:2117-2124.
• [14]Bird RP: Aberrant crypt foci system to study cancer preventive agents in the colon. In Tumor Marker Protocol. Edited by Hanausek M, Walaszek Z. New Jersey, USA: Human Press Inc; 1998:465-474.
• [15]Bird CL, Witte JS, Swendseid ME, Shikany JM, Hunt IF, Frankl HD, Lee ER, Longnecker MP, Haile RW: Plasma ferritin, iron intake, and the risk of colorectal polyps. Am J Epidemiol 1996, 144:34-41.
• [16]Rao PS, Liu X, Das DK, Weinstein GS, Tyras DH: Protection of ischemic heart from reperfusion injury by myo-inositol hexaphosphate a natural antioxidant. Ann Thorac Surg 1991, 52:908-912.
• [17]Kohno H, Suzuki R, Sugie S, Tanaka T: Suppression of colitis-related mouse colon carcinogenesis by a COX-2 inhibitor and PPAR ligands. BioMed Central Cancer 2005, 5:46-58.
• [18]Boateng J, Verghese M, Panala V, Walker LT, Shackelford L: Protective effects of rice bran on chemically induced colon tumorigenesis may be due to synergistic/additive properties of bioactive components. Int J Cancer Res 2009, 5:153-166.
• [19]Giles RH, van Es JH, Clevers H: Caught up in a Wnt storm: Wnt signaling in cancer. Biochim Biophys Acta 2003, 1653:1-24.
• [20]Spychalski M, Dziki L, Dziki A: Chemoprevention of colorectal cancer - a new target needed? Colorectal Dis 2007, 9:397-401.
• [21]Verheyen EM, Gottardi CJ: Regulation of Wnt/β-catenin signaling by protein kinases. Dev Dyn 2010, 239:34-44.
• [22]Paul S, DeCastro AJ, Lee HJ, Smolarek AK, So JY, Simi B, Wang CX, Zhou R, Rimando AM, Suh N: Dietary intake of pterostilbene, a constituent of blueberries, inhibits the β-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats. Carcinogenesis 2010, 31:1272-1278.
• [23]Bertagnolli MM: Chemoprevention of colorectal cancer with cyclooxygenase-2 inhibitors: two steps forward, one step back. Lancet Oncol 2007, 8:439-443.
• [24]Shao J, Sheng H, Aramandla R, Pereira MA, Lubert RA, Hawk E, Grogan L, Kirsch IR, Washington MK, Beauchamp RD, Dubois RN: Coordinate regulation of cyclooxygenase-2 and TGF-β 1 in replication error-positive colon cancer and azoxymethane-induced rat colonic tumors. Carcinogenesis 1999, 20:185-191.
• [25]Rao CV, Kawamori T, Hamid R, Reddy BS: Chemoprevention of colonic aberrant crypt foci by an inducible nitric oxide synthase-selective inhibitor. Carcinogenesis 1999, 20:641-644.
• [26]Tanaka T, Shimizu M, Kohno H, Yoshitani S, Tsukio Y, Murakami A, Safitri R, Takahashi D, Yamamoto K, Koshimizu K, Ohigashi H, Mori H: Chemoprevention of azoxymethane-induced rat aberrant crypt foci by dietary zerumbone isolated from Zingiberzerumbet. Life Sci 2001, 69:1935-1945.
• [27]Suzuki R, Miyamoto S, Yasui Y, Sugie S, Tanaka T: Global gene expression analysis of the mouse colonic mucosa treated with azoxymethane and dextran sodium sulfate. BMC Cancer 2007, 7:84.
• [28]Araki Y, Okamura S, Hussain P, Nagashima M, He P, Shiseki M, Miura K, Harris CC: Regulation of cyclooxygenase-2 expression by the Wnt and Ras pathways. Cancer Res 2003, 63:728-734.
• [29]Roschek BJ, Fink RC, Li D, McMichael M, Tower CM, Smith RD, Alberte RS: Pro-inflammatory enzymes, cyclooxygenase 1, cyclooxygenase 2, and 5-lipooxygenase, inhibited by stabilized rice bran extracts. J Med Food 2009, 12:615-623.
• [30]Norazalina S, Norhaizan ME, Hairuszah I: Suppression of β-catenin and cyclooxygenase-2 expression and cell proliferation in azoxymethane-induced colonic cancer in rats by rice bran phytic acid (PA). Asian Pacific J Cancer Prev 2013, 14:3093-3099.
• [31]Phutthaphadoong S, Yamada Y, Hirata A, Tomita H, Taguchi A, Hara A, Limtrakul PN, Iwasaki T, Kobayashi H, Mori H: Chemopreventive effects of fermented brown rice and rice bran against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in female A/J mice. Oncol Rep 2009, 21:321-327.
• [32]Li SC, Chou TC, Shih CK: Effects of brown rice, rice bran and polished rice on colon carcinogenesis in rats. Food Res Int 2011, 44:209-216.
• [33]Latifah SY, Armania N, Tze TH, Azhar Y, Nordiana AH, Norazalina S, Hairuszah I, Saidi M, Maznah I: Germinated brown rice (GBR) reduces the incidence of aberrant crypt foci with the involvement of β-catenin and COX-2 in azoxymethane-induced colon cancer in rats. Nutr J 2010, 9:16.
• [34]Liang Q, Steven JS, Basil R: Sulindacsulfide inhibits the proliferation of colon cancer cells: diminished expression of the proliferation markers PCNA and Ki-67. Cancer Lett 1997, 115:229-234.
• [35]Biasco G, Paganelli GM, Santucci R, Brandi C, Barbara L: Methodological problems in the use of rectal cell proliferation as a biomarker of colorectal cancer risk. J Cell Biochem 1994, 19:55-60.
• [36]Patel KR, Brown VA, Jones DJL, Britton RG, Hemingway D, Miller AS, West KP, Booth TD, Perloff M, Crowell JA, Brenner DE, Steward W, Gescher AJ, Brown K: Clinical pharmacology of Resveratrol and its metabolites in colorectal cancer patients. Cancer Res 2010, 70:7392-7399.
• [37]Barnes LD, Garrison PN, Siprashvili Z, Guranowski A, Robinson AK, Ingram SW, Croce CM, Ohta M, Huebner K: Fhit, a putative tumor suppressor in humans, is a dinucleoside 5’, 5”‘-P1, P3-triphosphate hydrolase. Biochemistry 1996, 35:11529-11535.
• [38]Khan N, Afaq F, Mukhtar H: Apoptosis by dietary factors: the suicide solution for delaying cancer growth. Carcinogenesis 2007, 28:233-239.
• [39]Wedge DE, Meepagala KM, Magee JB, Smith SH, Huang G, Larcom LL: Anticarcinogenic activity of strawberry, blueberry, and raspberry extracts to breast and cervical cancer cells. J Med Food 2001, 4:49-51.
• [40]Liu RH: Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemical. Am J Clin Nutr 2003, 3:517-520.
• [41]Tsuda H, Ohshima Y, Nomoto H, Fujita K, Matsuda E, Iigo M, Takasuka N, Moore MA: Cancer prevention by natural compounds. Drug Metab Pharmacokinet 2004, 19:245-263.
• [42]Ricciardiello L, Bazzoli F, Fogliano V: Phytochemicals and colorectal cancer prevention–myth or reality? Nature Reviews. Gastroenterol and Hepatol 2011, 8:592-596.
• [43]Shukla Y, George J: Combinatorial strategies employing nutraceuticals for cancer development. Ann New York Acad Sci 2011, 1229:162-175.
• [44]Cai H, Al-Fayez M, Tunstall RG, Platton S, Greaves P, Steward WP, Gescher AJ: The rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMinmice. Mol Cancer Ther 2005, 4:1287-1292.
• [45]Janicke B, Onning G, Oredsson SM: Differential effects of ferulic acid and p-Coumaric acid on S phase distribution and length of S phase in the human colonic cell line Caco-2. J Agric Food Chem 2005, 53:6658-6665.