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

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 16; no. 9; pp. 1767 - 1774
• Main Authors: CAMPBELL, Kristin L, MCTIERNAN, Anne, SURAWICZ, Christina, AYUB, Kamran, POTTER, John D, LAMPE, Paul D, LI, Shuying S, SORENSEN, Bess E, YASUI, Yutaka, LAMPE, Johanna W, KING, Irena B, ULRICH, Cornelia M, RUDOLPH, Rebecca E, IRWIN, Melinda L
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-09-2007
• Subjects: Adult; Aged; Apoptosis; bcl-2-Associated X Protein - biosynthesis; Biological and medical sciences; Colon - metabolism; Colon - pathology; colon cancer; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colonic Neoplasms - prevention & control; Exercise; Female; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Male; Medical sciences; Middle Aged; physical activity; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Sex Factors; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Time Factors; Tumors; United States; North America; America; Physical exercise; Human; Malignant tumor; Epidemiology; Colonic disease; Colon cancer; Cancerology; Cell death; C-Onc gene; Risk factor; Randomised controlled trial; Digestive diseases; Genetics; Intestinal disease; Public health; Protooncogene; Apoptosis
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-07-0291

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 (VO 2 max) 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)