Exercise training combined with antioxidant supplementation prevents the antiproliferative activity of single treatment in prostate cancer through inhibition of redox adaptation.
Abstract
In preclinical models, exercise training ET or pomegranate juice PJ individually prevents prostate cancer progression. Here, we hypothesize that physical exercise combined with antioxidants could induce synergistic effects through oxidative stress modulation. Forty male Copenhagen rats with prostate tumors were divided into four groups: Control, PJ, ET, PJ+ET. Rats from PJ group consumed daily 750µl of PJ, rats from ET group run on a treadmill 5 days per week and PJ+ET rats received the combined treatments. Each week, tumor growth was evaluated. After four weeks of treatment, rats were euthanized and blood, muscles and tumors were collected. Tumor Ki67, Extracellular signal-Regulated Kinase ERK activation, Bcl2 expression, enzymatic and non-enzymatic antioxidant defenses as well as oxidative stress markers (oxidized base, lipid peroxidation, protein carbonylation) were measured. PJ or ET significantly decreased prostate tumor proliferation (Ki67 staining, p<0.05) through the modulation of ERK phosphorylation whereas the association of treatments didn't limit cancer progression. PJ significantly reduced Bcl-2 expression in tumors (p<0.05) and the combination of PJ and ET prevented this effect. PJ or ET increased enzymatic antioxidant defenses in muscle, PJ increased non-enzymatic antioxidant defenses in plasma and whole blood. In addition, PJ reduced TBARS and 8-oxodGuo levels in tumors as well as ET (p<0.05) whereas protein carbonyl levels were not affected by these two strategies. Paradoxically, association of PJ+ET didn't increase antioxidant defenses and no reduction of oxidative stress markers was induced. Loading cancer cells with antioxidants blunts the positive effects of ET and interferes with important ROS-mediated physiological processes such as antioxidant adaptations.