Effect of a 12-Month Exercise Intervention on the Apoptotic Regulating Proteins Bax and Bcl-2 in Colon Crypts: A Randomized Controlled Trial

Cancer Epidemiology Biomarkers and Prevention - Tập 16 Số 9 - Trang 1767-1774 - 2007
Kristin L. Campbell1,2, Anne McTiernan2,3,4,1, Shuying S. Li1,2, Bess Sorensen1,2, Yutaka Yasui5, Johanna W. Lampe1,2,3, Irena B. King1,2, Cornelia M. Ulrich2, Robert H. Rudolph2,4,6,1, Melinda L. Irwin7, Christina M. Surawicz1,4, Kamran Ayub8, John D. Potter1,2,3, Paul D. Lampe2,9
1University of Washington
21Cancer Prevention Program, Division of Public Health Sciences, The Fred Hutchinson Cancer Research Center; Departments of
32Epidemiology,
43Medicine, and
57Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada; and
65Health Services Research and Development Program, Veterans Affairs Puget Sound Health Care System;
78Department of Public Health, Yale University School of Medicine, New Haven, Connecticut
86Virginia Mason Medical Center, Seattle, Washington;
94Pathobiology, University of Washington;

Tóm tắt

Abstract Background: Cellular proliferation and apoptosis (cell death) are highly regulated in the colon as insufficient apoptosis may lead to polyps and cancer. Physical activity decreases risk of colon cancer in observational studies, but the biological basis is not well defined. The objective of this study is to examine the effects of a 12-month aerobic exercise program on expression of proteins that promote (Bax) or inhibit (Bcl-2) apoptosis in colon crypts. Methods: Two hundred two sedentary participants, 40 to 75 years, were randomly assigned to moderate-to-vigorous intensity exercise for 60 min per day, 6 days per week for 12 months, or usual lifestyle. Colon crypt samples were obtained at baseline and 12 months. Bcl-2 and Bax expression was measured by immunohistochemistry. Results: Bax density at the bottom of crypts increased in male exercisers versus controls (+0.87 versus −0.18; P = 0.05), whereas the ratio of Bcl-2 to Bax at the bottom and middle of crypts decreased as aerobic fitness (VO2max) increased (P trend = 0.02 and 0.05, respectively). In female exercisers, Bax density in the middle of crypts decreased (−0.36 versus +0.69; P = 0.03) and Bcl-2 to Bax ratio at the top of crypts increased versus controls (+0.46 versus −0.85; P = 0.03). Bax density in the middle of crypts also decreased as minutes per week of exercise increased (P trend = 0.03). Conclusions: A 12-month exercise intervention resulted in greater expression of proteins that promote apoptosis at the bottom of colon crypts in men and decreased expression of proteins that promote apoptosis at the middle and top of colon crypts in women. The difference in effect by gender and location of observed changes warrants further study. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1767–74)

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Tài liệu tham khảo

Friedenreich CM, Orenstein MR. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr 2002;132:3456–64S.

Slattery ML, Edwards SL, Ma KN, Friedman GD, Potter JD. Physical activity and colon cancer: a public health perspective. Ann Epidemiol 1997;7:137–45.

Samad AK, Taylor RS, Marshall T, Chapman MA. A meta-analysis of the association of physical activity with reduced risk of colorectal cancer. Colorectal Dis 2005;7:204–13.

Kushi LH, Byers T, Doyle C, et al. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin 2006;56:254–81; quiz 313–4.

Shanmugathasan M, Jothy S. Apoptosis, anoikis and their relevance to the pathobiology of colon cancer. Pathol Int 2000;50:273–9.

Srivastava S, Verma M, Henson DE. Biomarkers for early detection of colon cancer. Clin Cancer Res 2001;7:1118–26.

Hockenbery DM, Zutter M, Hickey W, Nahm M, Korsmeyer SJ. BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death. Proc Natl Acad Sci U S A 1991;88:6961–5.

Hockenbery DM. bcl-2 in cancer, development and apoptosis. J Cell Sci Suppl 1994;18:51–5.

Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ, Levin B. bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res 1995;55:237–41.

Merritt AJ, Potten CS, Watson AJ, et al. Differential expression of bcl-2 in intestinal epithelia. Correlation with attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Sci 1995;108:2261–71.

Bosari S, Moneghini L, Graziani D, et al. bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. Hum Pathol 1995;26:534–40.

Bronner MP, Culin C, Reed JC, Furth EE. The bcl-2 proto-oncogene and the gastrointestinal epithelial tumor progression model. Am J Pathol 1995;146:20–6.

Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang HG, Reed JC. Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol 1994;145:1323–36.

McTiernan A, Yasui Y, Sorensen BE, et al. Effect of a 12-month exercise intervention on patterns of cellular proliferation in colonic crypts: a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 2006;15:1–10.

McTiernan A, Sorensen B, Irwin ML, et al. Exercise effect on weight and body fat in men and women. Obesity 2007;15:1496–512.

Shvartz E, Reibold RC. Aerobic fitness norms for males and females aged 6 to 75 years: a review. Aviat Space Envir Med 1990;61:3–11.

Schauer JE, Hanson P. Usefulness of a branching treadmill protocol for evaluation of cardiac functional capacity. Am J Cardiol 1987;60:1373–7.

Franklin BA, editor. ACSM's guidelines for exercise testing and prescription. Baltimore: Lippincott Williams & Wilkins; 2000.

Bird RP, McLellan EA, Bruce WR. Aberrant crypts, putative precancerous lesions, in the study of the role of diet in the aetiology of colon cancer. Cancer Surv 1989;8:189–200.

Cheng J, Ogawa K, Kuriki K, et al. Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors. Cancer Lett 2003;193:17–24.

Ladas SD, Kitsanta P, Triantafyllou K, Tzathas C, Spiliadi C, Raptis SA. Cell turnover of serrated adenomas. J Pathol 2005;206:62–7.

Dirks P, Freeman HJ. Effects of differing purified cellulose, pectin and hemicellulose fiber diets on mucosal morphology in the rat small and large intestine. Clin Invest Med 1987;10:32–8.

Heitman DW, Ord VA, Hunter KE, Cameron IL. Effect of dietary cellulose on cell proliferation and progression of 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. Cancer Res 1989;49:5581–5.

Andrianopoulos G, Nelson RL, Bombeck CT, Souza G. The influence of physical activity in 1,2 dimethylhydrazine induced colon carcinogenesis in the rat. Anticancer Res 1987;7:849–52.

Reddy BS, Sugie S, Lowenfels A. Effect of voluntary exercise on azoxymethane-induced colon carcinogenesis in male F344 rats. Cancer Res 1988;48:7079–81.

Demarzo MM, Garcia SB. Exhaustive physical exercise increases the number of colonic preneoplastic lesions in untrained rats treated with a chemical carcinogen. Cancer Lett 2004;216:31–4.

Colbert LH, Davis JM, Essig DA, Ghaffar A, Mayer EP. Exercise and tumor development in a mouse predisposed to multiple intestinal adenomas. Med Sci Sports Exerc 2000;32:1704–8.

Colbert LH, Mai V, Perkins SN, et al. Exercise and intestinal polyp development in APCMin mice. Med Sci Sports Exerc 2003;35:1662–9.

Calton BA, Lacey JV, Jr., Schatzkin A, et al. Physical activity and the risk of colon cancer among women: a prospective cohort study (United States). Int J Cancer 2006;119:385–91.

Slattery ML. Physical activity and colorectal cancer. Sports Med 2004;34:239–52.

Slattery ML, Ballard-Barbash R, Edwards S, Caan BJ, Potter JD. Body mass index and colon cancer: an evaluation of the modifying effects of estrogen (United States). Cancer Causes Control 2003;14:75–84.

McTiernan A, Tworoger SS, Ulrich CM, et al. Effect of exercise on serum estrogens in postmenopausal women: a 12-month randomized clinical trial. Cancer Res 2004;64:2923–8.

McTiernan A, Ulrich C, Slate S, Potter J. Physical activity and cancer etiology: associations and mechanisms. Cancer Causes Control 1998;9:487–509.

McMichael AJ, Potter JD. Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis. J Natl Cancer Inst 1980;65:1201–7.

Potter JD, McMichael AJ. Large bowel cancer in women in relation to reproductive and hormonal factors: a case-control study. J Natl Cancer Inst 1983;71:703–9.

Chlebowski RT, Wactawski-Wende J, Ritenbaugh C, et al. Estrogen plus progestin and colorectal cancer in postmenopausal women. N Engl J Med 2004;350:991–1004.

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Cancer Epidemiology Biomarkers and Prevention

Tập 16 Số 9

1767-1774

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