title: Obesity promotes aerobic glycolysis in prostate cancer cells.
abstract: Obesity is the leading preventable comorbidity associated with increased prostate cancer-related recurrence and mortality. Epidemiological and clinical studies indicate that a body mass index >30 is associated with increased oxidative DNA damage within the prostate gland and increased prostate cancer-related mortality. Here we provide evidence that obesity promotes worse clinical outcome through induction of metabolic abnormalities known to promote genotoxic stress. We have previously reported that blood serum derived from obese mice may enhance the proliferative and invasive potential of human prostate cancer cell lines ex vivo. Here we show that a 1-h exposure of LNCaP or PacMetUT1 prostate cancer cell lines and nonmalignant RWPE-1 prostate epithelial cells to 2% serum from obese mice induces markers of aerobic glycolysis relative to those exposed to serum from nonobese mice. This metabolic change was correlated with accumulation of reactive oxygen species (ROS) and increased frequency of DNA double-strand breaks. Interestingly, N-tert-Butylhydroxylamine, an antioxidant, significantly suppressed markers of aerobic glycolysis in the cells exposed to the blood serum of obese mice, suggesting that ROS contributes to a metabolic shift toward aerobic glycolysis. Here we describe obesity-induced changes in key metabolic markers that impact prostate cancer cell progression and explore the role of antioxidants in ameliorating these effects.
authors.affiliation: a Department of Nutritional Sciences , University of Texas at Austin , Austin , Texas , USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Cavazos
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: deGraffenried
authors.forename: Shruti A
authors.initials: SA
authors.lastname: Apte
authors.forename: Laura W
authors.initials: LW
authors.lastname: Bowers
authors.forename: Kaitlin A
authors.initials: KA
authors.lastname: Whelan
authors.forename: Linda A
authors.initials: LA
authors.lastname: deGraffenried
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D018450:Disease Progression; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D011770:Pyruvate Kinase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000975:Antioxidants; D006898:Hydroxylamines; D017382:Reactive Oxygen Species; C072771:N-tert-butylhydroxylamine; D011770:Pyruvate Kinase