This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Campbell, K. L. Articles by Lampe, P. D. Search for Related Content PubMed PubMed Citation Articles by Campbell, K. L. Articles by Lampe, P. D.

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

¹ Cancer Prevention Program, Division of Public Health Sciences, The Fred Hutchinson Cancer Research Center; Departments of ² Epidemiology, ³ Medicine, and ⁴ Pathobiology, University of Washington; ⁵ Health Services Research and Development Program, Veterans Affairs Puget Sound Health Care System; ⁶ Virginia Mason Medical Center, Seattle, Washington; ⁷ Department of Public Health Sciences, University of Alberta, Edmonton, Alberta, Canada; and ⁸ Department 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

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)