Prostate cancer cell growth characteristics in serum and prostate-conditioned media from moderate-intensity exercise-trained healthy and tumor-bearing rats

Alexander B Opoku-Acheampong; Dryden R Baumfalk; Andrew G Horn; Olivia N Kunkel; Charan K Ganta; Danielle J McCullough; Dietmar W Siemann; Judy Muller-Delp; Bradley J Behnke

Prostate cancer cell growth characteristics in serum and prostate-conditioned media from moderate-intensity exercise-trained healthy and tumor-bearing rats

Am J Cancer Res. 2019 Apr 1;9(4):650-667. eCollection 2019.

Authors

Alexander B Opoku-Acheampong¹, Dryden R Baumfalk¹, Andrew G Horn¹, Olivia N Kunkel¹, Charan K Ganta², Danielle J McCullough³, Dietmar W Siemann⁴, Judy Muller-Delp⁵, Bradley J Behnke¹

Affiliations

¹ Department of Kinesiology, Kansas State University Manhattan, KS 66506, USA.
² Department of Diagnostic Medicine, College of Veterinary Medicine, Kansas State University Manhattan, KS 66506, USA.
³ Department of Anatomy and Physiology, Edward Via College of Osteopathic Medicine-Auburn Campus Auburn, AL 36832, USA.
⁴ Department of Radiation Oncology, University of Florida Gainesville, FL 32610, USA.
⁵ Department of Biomedical Sciences, College of Medicine, Florida State University Tallahassee, FL 32306, USA.

PMID: 31105994
PMCID: PMC6511645

Abstract

Physical activity is associated with diminished risk of several cancers, and preclinical studies suggest exercise training may alter tumor cell growth in certain tissue(s) (e.g., adipose). From moderate-intensity exercise-trained rats versus sedentary controls, we hypothesized 1) there will be a decreased prostate cancer cell viability and migration in vitro and, within the prostate, a reduced 5α-reductase 2 (5αR2) and increased caspase-3 expression, and 2) that exercise training in tumor-bearing (TB) animals will demonstrate a reduced tumor cell viability in prostate-conditioned media. Serum and prostate were harvested from sedentary or exercise-trained (treadmill running, 10-11 weeks) immune-competent (Copenhagen; n = 20) and -deficient (Nude; n = 18) rats. AT-1 and PC-3 prostate cancer cells were grown in one or more of the following: serum-supplemented media (SSM), SSM from TB rats (SSM-TB), prostate-conditioned media (PCM) or PCM from TB rats (PCM-TB) for 24-96 h under normoxic (18.6% O₂) or hypoxic (5% O₂) conditions. Under normoxic condition, there was a decreased AT-1 cell viability in SSM and PCM from the exercise-trained (ET) immune-competent rats, but no difference in PC-3 cell viability in SSM and PCM from ET Nude rats versus the sedentary (SED) group, or in SSM-TB from ET-TB Nude rats versus the SED-TB group. However, there was a decreased PC-3 cell viability in the PCM-TB of the ET-TB group versus SED-TB group. PC-3 cell viability in all conditioned media types was not altered between groups with hypoxia. In the prostate, exercise training did not alter 5αR2 expression levels, but increased caspase-3 expression levels. In conclusion, prior exercise status reduced prostate cancer cell viability in the serum and prostate of trained rats but did not modify several other key prostate tumor cell growth characteristics (e.g., migration, cell cycle except in S phase of PC-3 cells in PCM-TB). Importantly, once the tumor was established, exercise training reduced tumor cell viability in the surrounding prostate, which may help explain the reduced severity of the disease in patients that exercise.

Keywords: 5α-reductase 2; Exercise; caspase-3; growth characteristics; hypoxia; normoxia; prostate cancer.