Exercise training combined with antioxidant supplementation prevents the antiproliferative activity of their single treatment in prostate cancer through inhibition of redox adaptation |
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| Institution: | 1. EA 1274, Laboratoire “Mouvement, Sport, Santé,“ Université de Rennes 2-ENS Rennes, Bruz 35170, France;2. Laboratoire “Lésions des Acides Nucléiques,” Université Joseph Fourier—Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France;1. Digestive Endoscopy Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy;2. Department of Medicine, Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy;3. Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy;4. Istituto di Ricerca Pediatrica—Città della Speranza, Padua, Italy;5. Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, TX, USA;6. Department of Molecular Medicine, University of Padua, Padua, Italy;7. Venetian Institute of Molecular Medicine-VIMM, Padua, Italy;1. Oncology Department, Kaiser Permanente Colorado, Lone Tree, CO;2. Institute for Health Research, Kaiser Permanente Colorado, Denver, CO;3. Division of Research, Kaiser Permanente Northern California, Oakland, CA;4. Pharmacy Department, Kaiser Permanente Colorado, Aurora, CO;5. The Center for Health Research, Kaiser Permanente Northwest, Portland, OR;6. Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA;7. Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA;8. Division of Hematology and Oncology, Department of Internal Medicine, University of California Davis School of Medicine, Sacramento, CA;3. From the Department of Biochemistry and Molecular Biology, Stanley S. Scott Cancer Center, School of Medicine and;4. the Department of Oral Biology, Louisiana State University Health Science Center, New Orleans, Louisiana 70112;1. Division of Bioengineering and LUTD Research, Nihon University School of Engineering, Koriyama City, Fukushima, Japan;2. Department of Pharmacology, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan;3. Department of Urology, Fukushima Medical University School of Medicine, Fukushima City, Fukushima, Japan;1. Department of Pediatrics, Second Affiliated Hospital of Jiaxing University, Jiaxing, ZJ, China;2. Department of Pathology and Molecular Medicine Center, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing University, Jiaxing, ZJ, China |
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| Abstract: | In preclinical models, exercise training (ET) or pomegranate juice (PJ) prevents prostate cancer progression. Here, we hypothesized 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, and PJ+ET. Rats from the PJ group consumed 750 µl of PJ daily, rats from the ET group ran on a treadmill 5 days per week, and PJ+ET rats received the combined treatment. Each week, tumor growth was evaluated. After 4 weeks of treatment, the rats were euthanized and blood, muscles, and tumors were collected. Tumor Ki67, extracellular signal-regulated kinase (ERK) activation, Bcl-2 expression, and enzymatic and nonenzymatic 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 combination of treatments did not 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 nonenzymatic 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 did not increase antioxidant defenses and no reduction in oxidative stress markers was induced. Loading cancer cells with antioxidants blunts the positive effects of ET and interferes with important reactive oxygen species-mediated physiological processes such as antioxidant adaptations. |
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| Keywords: | Prostate cancer Pomegranate juice Physical exercise Oxidative stress Antioxidant adaptation Free radicals |
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