title: Exploratory studies of the potential anti-cancer effects of creatine.
abstract: Two experiments were performed, in which male Wistar Walker 256 tumor-bearing rats were inoculated with 4 × 10(7) tumor cells subcutaneously and received either creatine (300 mg/kg body weight/day; CR) or placebo (water; PL) supplementation via intragastric gavage. In experiment 1, 50 rats were given PL (n = 22) or CR (n = 22) and a non-supplemented, non-inoculated group served as control CT (n = 6), for 40 days, and the survival rate and tumor mass were assessed. In experiment 2, 25 rats were given CR or PL for 15 days and sacrificed for biochemical analysis. Again, a non-supplemented, non-inoculated group served as control (CT; n = 6). Tumor and muscle creatine kinase (CK) activity and total creatine content, acidosis, inflammatory cytokines, and antioxidant capacity were assessed. Tumor growth was significantly reduced by approximately 30 % in CR when compared with PL (p = 0.03), although the survival rate was not significantly different between CR and PL (p = 0.65). Tumor creatine content tended to be higher in CR than PL (p = 0.096). Tumor CK activity in the cytosolic fraction was higher in CR than PL (p < 0.0001). Blood pCO2 was higher in CT and CR than PL (p = 0.0007 and p = 0.004, respectively). HCO3 was augmented in CT compared to PL (p = 0.03) and CR (p = 0.001). Plasma IL-6 was lower and IL-10 level was higher in CR than PL (p = 0.03 and p = 0.0007, respectively) and TNF-alpha featured a tendency of decrease in CR compared to PL (p = 0.08). Additionally, total antioxidant capacity tended to be lower in CT than PL (p = 0.07). Creatine supplementation was able to slow tumor growth without affecting the overall survival rate, probably due to the re-establishment of the CK-creatine system in cancer cells, leading to attenuation in acidosis, inflammation, and oxidative stress. These findings support the role of creatine as a putative anti-cancer agent as well as help in expanding our knowledge on its potential mechanisms of action in malignancies.
authors.affiliation: School of Physical Education and Sport, Department of Biodynamics, University of São Paulo, São Paulo, SP, Brazil. plcampos@usp.br.|Faculty of Applied Sciences, State University of Campinas, Limeira, SP, Brazil. plcampos@usp.br.
authors.forename: P L
authors.initials: PL
authors.lastname: Campos-Ferraz
authors.affiliation: School of Physical Education and Sport, Department of Biodynamics, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: B
authors.initials: B
authors.lastname: Gualano
authors.affiliation: School of Physical Education and Sport, Department of Biodynamics, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: W
authors.initials: W
authors.lastname: das Neves
authors.affiliation: School of Physical Education and Sport, Department of Biodynamics, University of São Paulo, São Paulo, SP, Brazil.|Faculty of Applied Sciences, State University of Campinas, Limeira, SP, Brazil.
authors.forename: I T
authors.initials: IT
authors.lastname: Andrade
authors.affiliation: School of Physical Education and Sport, Department of Biodynamics, University of São Paulo, São Paulo, SP, Brazil.|Faculty of Public Health, University of Sao Paulo, São Paulo, SP, Brazil.
authors.forename: I
authors.initials: I
authors.lastname: Hangai
authors.affiliation: School of Physical Education and Sport, Department of Biodynamics, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: R T S
authors.initials: RT
authors.lastname: Pereira
authors.affiliation: Faculty of Applied Sciences, State University of Campinas, Limeira, SP, Brazil.
authors.forename: R N
authors.initials: RN
authors.lastname: Bezerra
authors.affiliation: Department of Physical Education, State University of Londrina, Londrina, PR, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Deminice
authors.affiliation: Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, SP, Brazil.|Faculty of Medicine, University of Sao Paulo, São Paulo, SP, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Seelaender
authors.affiliation: School of Physical Education and Sport, Department of Biodynamics, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: A H
authors.initials: AH
authors.lastname: Lancha
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D003401:Creatine / Q000493:pharmacokinetics / Q000494:pharmacology*; D052283:Creatine Kinase, MM Form / Q000378:metabolism*; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D052283:Creatine Kinase, MM Form; D003401:Creatine
keywords: Diet; Malignancy; Supplementation; Tumor