title: Exercise training combined with antioxidant supplementation prevents the antiproliferative activity of their single treatment in prostate cancer through inhibition of redox adaptation.
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.
authors.affiliation: EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France.
authors.forename: Jordan
authors.initials: J
authors.lastname: Gueritat
authors.affiliation: EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France.
authors.forename: Luz
authors.initials: L
authors.lastname: Lefeuvre-Orfila
authors.affiliation: EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Vincent
authors.affiliation: EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France.
authors.forename: Armel
authors.initials: A
authors.lastname: Cretual
authors.affiliation: Laboratoire "Lésions des Acides Nucléiques," Université Joseph Fourier-Grenoble 1/CEA/Institut Nanoscience et Cryogénie/SCIB, UMR-E3, Grenoble, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Ravanat
authors.affiliation: EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France.
authors.forename: Arlette
authors.initials: A
authors.lastname: Gratas-Delamarche
authors.affiliation: EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Rannou-Bekono
authors.affiliation: EA 1274, Laboratoire "Mouvement, Sport, Santé," Université de Rennes 2-ENS Rennes, Bruz 35170, France. Electronic address: amelie.rebillard@univ-rennes2.fr.
authors.forename: Amélie
authors.initials: A
authors.lastname: Rebillard
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005638:Fruit / Q000737:chemistry; D029561:Lythraceae / Q000737:chemistry; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009368:Neoplasm Transplantation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D010936:Plant Extracts / Q000008:administration & dosage*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D013482:Superoxide Dismutase; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Antioxidant adaptation; Free radicals; Oxidative stress; Physical exercise; Pomegranate juice; Prostate cancer