Effect of a 12-Month Exercise Intervention on the Apoptotic Regulating Proteins Bax and Bcl-2 in Colon Crypts: A Randomized Controlled Trial
- Kristin L. Campbell1,
- Anne McTiernan1,2,3,
- Shuying S. Li1,
- Bess E. Sorensen1,
- Yutaka Yasui7,
- Johanna W. Lampe1,2,
- Irena B. King1,
- Cornelia M. Ulrich1,
- Rebecca E. Rudolph1,3,5,
- Melinda L. Irwin8,
- Christina Surawicz3,
- Kamran Ayub6,
- John D. Potter1,2 and
- Paul D. Lampe1,4
- 1Cancer Prevention Program, Division of Public Health Sciences, The Fred Hutchinson Cancer Research Center; Departments of 2Epidemiology, 3Medicine, and 4Pathobiology, University of Washington; 5Health Services Research and Development Program, Veterans Affairs Puget Sound Health Care System; 6Virginia Mason Medical Center, Seattle, Washington; 7Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada; and 8Department of Public Health, Yale University School of Medicine, New Haven, Connecticut
- Requests for reprints:
Anne McTiernan, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024. Phone: 206-667-7979; Fax: 206-667-7850. E-mail: amctiern{at}fhcrc.org
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)
Footnotes
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↵9 Available at http://rsb.info.nih.gov/nih-image/.
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Grant support: National Cancer Institute grant RO1 CA 77572-01. K.L. Campbell is supported by a Canadian Institutes of Health Research Fellowship.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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Disclaimer: The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs.
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- Accepted July 2, 2007.
- Received April 3, 2007.
- Revision received May 31, 2007.
