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Non-digestible fraction of beans (Phaseolus vulgaris L.) modulates signalling pathway genes at an early stage of colon cancer in Sprague–Dawley rats

  • Vergara-Castañeda Haydé (a1), Guevara-González Ramón (a2), Guevara-Olvera Lorenzo (a3), Oomah B. Dave (a4), Reynoso-Camacho Rosalía (a1), Wiersma Paul (a4) and Loarca-Piña Guadalupe (a1)...

Colorectal cancer is one of the most common causes of morbidity and mortality in Western countries, the second cause of cancer mortality in the USA and a major public health problem in Mexico. A diet rich in legumes is directly related to the prevention of colon cancer, showing an inverse relationship with the development of colorectal adenomas in human subjects. The present study shows the results of molecular changes involved in the Tp53 pathway at an early stage in the distal colon tissue of azoxymethane (AOM)-induced colon cancer in rats evaluated by PCR array after exposure to diets containing the non-digestible fraction (NDF) of cooked bean (cultivar Bayo Madero). Significant differences were detected in seventy-two genes of the Tp53-mediated signalling pathway involved in apoptosis, cell-cycle regulation and arrest, inhibition of proliferation and inflammation, and DNA repair. Tp53, Gadd45a, Cdkn1a and Bax were highly expressed (9·3-, 18·3-, 5·5- and 3·5-fold, respectively) in the NDF+AOM group, whereas Cdc25c, Ccne2, E2f1 and Bcl2 were significantly suppressed ( − 9·2-, − 2·6-, − 18·4- and − 3·5-fold, respectively), among other genes, compared with the AOM group, suggesting that chemoprevention of aberrant crypt foci results from a combination of cell-cycle arrest in G1/S and G2/M phases and cell death by apoptotic induction. We demonstrate that the NDF from common bean modulates gene expression profiles in the colon tissue of AOM-induced rats, contributing to the chemoprotective effect of common bean on early-stage colon cancer.

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      Non-digestible fraction of beans (Phaseolus vulgaris L.) modulates signalling pathway genes at an early stage of colon cancer in Sprague–Dawley rats
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      Non-digestible fraction of beans (Phaseolus vulgaris L.) modulates signalling pathway genes at an early stage of colon cancer in Sprague–Dawley rats
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      Non-digestible fraction of beans (Phaseolus vulgaris L.) modulates signalling pathway genes at an early stage of colon cancer in Sprague–Dawley rats
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Corresponding author
*Corresponding author: L.-P. Guadalupe, fax +52 442 192 1307, email
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1Jemal A, Siegel R, Ward E, et al. (2006) Cancer statistics, 2006. CA Cancer J Clin 56, 106130.
2Jemal A, Siegel R, Xu J, et al. (2010) Cancer statistics, 2010. CA Cancer J Clin 60, 277300.
3Instituto Nacional de Estadísticas, Geografía e Informática (2008), Mexico. Información sobre Tumores Malignos (National Institute of Statistics, Geography and Informatics, Mexico. Information on Malignant Tumors): INEGI.
4Michels KB (2005) The role of nutrition in cancer development and prevention. Int J Cancer 114, 163165.
5Millen AE, Subar AF, Grawbard BI, et al. (2007) Fruit and vegetable intake and prevalence of colorectal adenoma in a cancer screening trial. Am J Clin Nutr 86, 17541764.
6Lanza E, Hartman TJ, Albert PS, et al. (2006) High dry bean intake and reduced risk of advanced colorectal adenoma recurrence among participants in the Polyp Prevention Trial. J Nutr 136, 18961903.
7Vergara-Castañeda HA, Guevara-Gonzalez RG, Ramos-Gómez M, et al. (2010) Non-digestible fraction of cooked bean (Phaseolus vulgaris L.) cultivar Bayo Madero suppresses colonic aberrant crypt foci in azoxymethane-induced rats. Food Funct 1, 294300.
8Torruco-Uco J, Chel-Guerrero L, Martínez-Ayala A, et al. (2009) Angiotensin-I converting enzyme inhibitory and antioxidant activities of protein hydrolysates from Phaseolus lunatus and Phaseolus vulgaris seeds. Food Sci Technol 42, 15971604.
9Campos-Vega R, Reynoso-Camacho R, Pedraza-Aboytes G, et al. (2009) Chemical composition and in vitro polysaccharide fermentation of different beans (Phaseolus vulgaris L.). J Food Sci 74, 5965.
10Chen J, Ghazawi FM, Bakkar W, et al. (2006) Valproic acid and butyrate induce apoptosis in human cancer cells through inhibition of gene expression of Akt/protein kinase B. Mol Cancer 5, 71.
11Veeriah S, Hofmann T, Glei M, et al. (2007) Apple polyphenols and products formed in the gut differently inhibit survival of human cell lines derived from colon adenoma (LT97) and carcinoma (HT29). J Agric Food Chem 55, 28922900.
12Kuntz S, Kunz C & Rudloff S (2009) Oligosaccharides from human milk induce growth arrest via G2/M by influencing growth-related cell cycle genes in intestinal epithelial cells. Br J Nutr 101, 13061315.
13Feregrino-Pérez AA, Berumen LC, García-Alcocer G, et al. (2008) Composition and chemopreventive effect of polysaccharides from common beans (Phaseolus vulgaris L.) on azoxymethane-induced colon cancer. J Agric Food Chem 56, 87378744.
14Campos-Vega R, Guevara-Gonzalez RG, Guevara-Olvera BL, et al. (2010) Bean (Phaseolus vulgaris L.) polysaccharides modulate gene expression in human colon cancer cells (HT-29). Food Res Int 43, 10571064.
15Aparicio-Fernández XO, Manzo-Bonilla L & Loarca-Piña GF (2005) Comparison of antimutagenic activity of phenolic compounds in newly harvested and stored common beans Phaseolus vulgaris against aflatoxin B1. J Food Sci 70, S73S78.
16Kurtzman RH & Halbrook WU (1970) Polysaccharide from dry navy beans, Phaseolus vulgaris: its isolation and stimulation of clostridium perfringens. Appl Microbiol 20, 715719.
17Del Razo LM, Garcia-Vargas GG, Garcia-Salcedo J, et al. (2002) Arsenic levels in cooked food and assessment of adult dietary intake of arsenic in the Region Lagunera, Mexico. Food Chem Toxicol 40, 14231431.
18Ho J & Benchimol S (2003) Transcriptional repression mediated by the p53 tumour suppressor. Cell Death Differ 10, 404408.
19Rahman-Roblick R, Roblick UJ, Hellman U, et al. (2007) p53 targets identified by protein expression profiling. PNAS 104, 54015406.
20Li L, Rao JN, Guo X, et al. (2001) Polyamine depletion stabilizes p53 resulting in inhibition of normal intestinal epithelial cell proliferation. Am J Physiol Cell Physiol 281, 941953.
21Mahyar-Roemer M & Roemer K (2001) p21 Waf1/Cip1 can protect human colon carcinoma cells against p53-dependent and p53-independent apoptosis induced by natural chemopreventive and therapeutic agents. Oncogene 20, 33873398.
22Damia G & Broggini M (2004) Cell cycle checkpoint proteins and cellular response to treatment by anticancer agents. Cell Cycle 3, 4650.
23Maeda T, Chong MT, Espino RA, et al. (2002) Role of p21Waf-1 in regulating the G1 and G2/M checkpoints in ultraviolet-irradiated keratinocytes. J Invest Dermatol 119, 513521.
24Foijer F & Te Riele H (2006) Restriction beyond the restriction point: mitogen requirement for G2 passage. Cell Div 1, 15.
25Robertson KD, Ait-Si-Ali S, Yokochi T, et al. (2000) DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters. Nat Genet 25, 338342.
26Robert MF, Morin S, Beaulieu N, et al. (2003) DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet 33, 6165.
27Harford TJ, Shaltouki A & Weyman CM (2010) Increased expression of the pro-apoptotic Bcl2 family member PUMA and apoptosis by the muscle regulatory transcription factor MyoD in response to a variety of stimuli. Apoptosis 15, 7182.
28Kawakami K, Ruszkiewicz A, Bennett G, et al. (2006) DNA hypermethylation in the normal colonic mucosa of patients with colorectal cancer. Br J Cancer 94, 593598.
29Hiranuma C, Kawakami K, Oyama K, et al. (2004) Hypermethylation of the MYOD1 gene is a novel prognostic factor in patients with colorectal cancer. Int J Mol Med 13, 413417.
30Imbriano C, Gurtner A, Cocchiarella F, et al. (2005) Direct p53 transcriptional repression: in vivo analysis of CCAAT-containing G2/M promoters. Mol Cell Biol 25, 37373751.
31Hildesheim J & Fornace AJ (2002) Gadd45a: an elusive yet attractive candidate gene in pancreatic cancer. Clin Cancer Res 8, 24752479.
32Jung HJ, Kim EH, Mun JY, et al. (2007) Base excision DNA repair defect in Gadd45a-deficient cells. Oncogene 26, 75177525.
33Li M, Liu L, Wang Z, et al. (2008) Overexpression of hMSH2 and hMLH1 protein in certain gastric cancers and their surrounding mucosae. Oncol Rep 19, 401406.
34Sengupta S & Roychoudhury S (2005) DNA double strand break and repair: mechanisms and involvement in human cancer. Int J Hum Genet 5, 110.
35Hermeking H, Lengauer C, Polyak K, et al. (1997) 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell 1, 311.
36Laronga C, Yang HY, Neal C, et al. (2000) Association of the cyclin-dependent kinases and 14-3-3 sigma negatively regulates cell cycle progression. J Biol Chem 275, 2310623112.
37Luk SCW, Siu SWF, Lai CK, et al. (2005) Cell cycle arrest by a natural product via G2/M checkpoint. Int J Med Sci 2, 6469.
38Lam EWF, Francis RE & Petkovic M (2006) FOXO transcription factors: key regulators of cell fate. Biochem Soc Trans 34, 722726.
39Greer EL & Brunet A (2005) FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24, 74107425.
40You H, Yamamoto K & Mak TW (2006) Regulation of transactivation-independent proapoptotic activity of p53 by FOXO3a. PNAS 103, 90519056.
41Frame S & Balmain A (2000) Integration of positive and negative growth signals during Ras pathway activation in vivo. Curr Opin Genet Dev 10, 06113.
42O'Brate A & Giannakakou P (2003) The importance of p53 location: nuclear or cytoplasmic zip code? Bax-induced apoptotic cell death. Drug Resist Updat 6, 313322.
43Pawlowski J & Kraft AS (2000) Bax-induced apoptotic cell death. PNAS 97, 529531.
44Bai J & Meng Z (2005) Expression of apoptosis-related genes in livers from rats exposed to sulfur dioxide. Toxicology 216, 253260.
45Ray R, Chen G, Velde CV, et al. (2000) BNIP3 heterodimerizes with Bcl-2/Bcl-XL and induces cell death independent of a Bcl-2 homology 3 (BH3) domain at both mitochondrial and nonmitochondrial sites. J Biol Chem 275, 14391448.
46Chen L, Willis SN, Wei A, et al. (2005) Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell 17, 393403.
47Marsden VS, Ekert PG, Van Delft M, et al. (2004) Bcl-2-regulated apoptosis and cytochrome c release can occur independently of both caspase-2 and caspase-9. J Cell Biol 165, 775780.
48Shrivastava A, Tiwari M, Sinha RA, et al. (2006) Molecular iodine induces caspase-independent apoptosis in human breast carcinoma cells involving the mitochondria-mediated pathway. J Biol Chem 281, 1976219771.
49Ravagnan L, Roumier T & Kroemer G (2002) Mitochondria, the killer organelles and their weapons. J Cell Physiol 192, 131137.
50Yu Z, Li W & Liu F (2004) Inhibition of proliferation and induction of apoptosis by genistein in colon cancer HT-29 cells. Cancer Lett 215, 159166.
51Agrawal S, Agarwal ML, Chatterjee-Kishore M, et al. (2002) Stat1-dependent, p53-independent expression of p21waf1 modulates oxysterol-induced apoptosis. Mol Cell Biol 22, 19811992.
52Lin YL, Sengupta S, Gurdziel K, et al. (2009) p63 and p73 transcriptionally regulate genes involved in DNA repair. PLoS Genet 5, 113.
53Flores ER, Tsai KY, Crowley D, et al. (2002) p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416, 560564.
54Haier J & Nicolson GL (2002) PTEN regulates tumor cell adhesion of colon carcinoma cells under dynamic conditions of fluid flow. Oncogene 21, 14501460.
55Campbell KJ, Rocha S & Perkins ND (2004) Active repression of antiapoptotic gene expression by RelA (p65) NF-κB. Mol Cell 13, 853865.
56Fujioka S, Schmidt C, Sclabas GM, et al. (2004) Stabilization of p53 is a novel mechanism for proapoptotic function of NF-κB. J Biol Chem 279, 2754927559.
57Wu ZH & Miyamoto S (2008) Induction of a pro-apoptotic ATM-NF-κB pathway and its repression by ATR in response to replication stress. EMBO J 27, 19631973.
58Maeda S & Karin M (2003) Oncogene at last c-Jun promotes liver cancer in mice. Cancer Cell 3, 102104.
59Cahill CM & Rogers JT (2008) Interleukin (IL) 1β induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/Iβ kinase α pathway targeting activator protein-1. J Biol Chem 283, 2590025912.
60Ahn KS & Aggarwal BB (2005) Transcription factor NF-κB. A sensor for smoke and stress signals. Ann NY Acad Sci 1056, 218233.
61Clemo NK, Collard TJ, Southern SL, et al. (2008) BAG-1 is up-regulated in colorectal tumour progression and promotes colorectal tumour cell survival through increased NF-κB activity. Carcinogenesis 29, 849857.
62Chen WC, Liu Q, Fu XJ, et al. (2004) Expression of survivin and its significance in colorectal cancer. World J Gastroenterol 10, 28862889.
63Ohki R, Nemoto J, Murasawa H, et al. (2004) Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2 phase. J Biol Chem 275, 2262722630.
64Nair VD, Yuen T, Olanow CW, et al. (2004) Early single cell bifurcation of pro- and antiapoptotic states during oxidative stress. J Biol Chem 279, 2749427501.
65Iacomino G, Tecce MF, Grimaldi C, et al. (2001) Transcriptional response of a human colon adenocarcinoma cell line to sodium butyrate. Biochem Biophys Res Commun 285, 12801289.
66Kosinski C, Li VSW, Chan ASY, et al. (2007) Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. PNAS 104, 1541815423.
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