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 (300mg/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 40days, and the survival rate and tumor mass were assessed. In experiment 2, 25 rats were given CR or PL for 15days 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.