A mechanism to explain how regular exercise might reduce the risk for clinical prostate cancer.
Epidemiological studies report that regular physical activity can reduce the risk for prostate cancer. This study was conducted to investigate possible mechanisms to explain the epidemiological data. Serum from sedentary controls or men with regular (5 days/week) aerobic exercise was used to stimulate lymph node cancer of the prostate (LNCaP) tumor cells in vitro. Growth and apoptosis were assessed and cell lysate p53, p21 and Bcl-2 proteins measured. Tryphostin was used to block the insulin-like growth factor-I receptor. Exercise serum-stimulated growth was reduced at 2 and 4 days while apoptosis was increased. Tryphostin reduced growth in the control but not in the exercise serum-stimulated samples. Total cell lysate p53 protein was higher in the exercise serum-stimulated cells at both 2 and 4 days. The levels of p21 protein, a downstream effector of p53, were elevated at 2 days but were normal at 4 days. Bcl-2, an antiapoptotic protein, was significantly reduced at 2 days in the exercise serum-stimulated lysates. These results indicate that exercise training alters serum insulin-like growth factor axis factors in vivo that increase LNCaP cellular p53 protein content in vitro leading to reduced growth via p21 and induced apoptosis via the mitochondrial pathway.
Barnard
R James
RJ
Department of Physiological Science, University of California, Los Angeles, Los Angeles, California 90095-1606, USA. jbarnard@physci.ucla.edu
Leung
Pak Shan
PS
Aronson
William J
WJ
Cohen
Pinchas
P
Golding
Lawrence A
LA
D017209:Apoptosis; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D015444:Exercise; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D012306:Risk; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018970:Insulin-Like Growth Factor Binding Protein 1; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I