Involvement of oxidative stress in prostate cancer progression: a preventive effect of physical activity and/or pomegranate juice?
Résumé
Introduction: Prostate cancer (PC) is the most common form of cancer affecting men in the Western world. Various studies suggest a decrease of PC evolution with exercise or antioxidants but the association of these two strategies has never been investigated. We hypothesize that oxidative stress is a key regulator factor of PC. In this context, we suppose that the potential decrease of oxidative stress (OS) induced by pomegranate juice (PJ) consumption alone, running training alone or the associated strategies could delay the development of PC. The objectives of this project are (1) to identify the effect of PJ and/or physical activity on PC progression in a rodent model; (2) to determine the molecular mechanisms involved in this prevention. Methods: Forty male Copenhagen rats with subcutaneous prostate tumor are divided into four groups: (1) control, (2) daily consumption of pomegranate juice PJ, (3) daily running on a treadmill (training), (4) PJ + training. Each week, tumor growth is evaluated using a sliding caliper. Four weeks after the various treatments, the rodents are sacrificed. The tumors are resected and frozen. Muscles (EDL, soleus, gastrocnemus and tibialis) are removed as well as blood and urine. The levels of antioxidant vitamins, antioxidant enzyme activities, lipid peroxidation, carbonylated proteins and DNA oxidation are investigated and the signaling pathways are identified. Data are compared by analysis of variance (ANOVA) and the degree of significance is set at p<0.05. Results: PJ consumption alone or training alone decreases prostate tumor growth in the Copenhagen rat (p<0.05) but the association of the two strategies is not also effective. Indeed, tumor volume doubling time is respectively of about six days for control and PJ+ training, whereas it is of eight days for PJ alone or training alone. We observe a significant difference of reduced GSH and vitamin A between PJ and control groups (p<0.05). Moreover, training increases significantly GPx activity vs control and PJ groups (p<0.05). The combination of PJ and training inhibits antioxidant adaptations induced by each treatment. Discussion: Although none study has demonstrated the benefits of both PJ and training, urologists recommend consumption of food antioxidants associated with physical exercise as chemoprevention for active monitoring PC patients. However our innovative study shows for the first time that combined effects of PJ and training may inhibit antioxidant adaptations and could prevent the modulation of redox-dependent signaling pathways involved in the prostate tumorigenesis.