Nexrutine, a Viable Exercise Mimetic for Prostate Cancer Prevention

Abstract

Epidemiological data suggests that physical activity (PA) has the potential to decrease the risk of high-grade prostate cancer (PCa). However, for various reasons, cancer patients fail to meet minimum standards for physical activity. For this reason, efforts need to be made to discover biologics that confer the physiological benefits of exercise, serving as an “exercise mimetic.” Previous work by our group has discovered that the natural product Nexrutine® (Nx), a bark extract of the phellodendrun amurense, can inhibit tumor development in prostate, pancreatic and skin cancers. PURPOSE: To compare the effectiveness of Nx and exercise in modulating carcinogenesis of the prostate using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. METHODS: 10-week old, male TRAMP mice were randomized to exercise, Nx or control groups (n=15 each). Mice randomized to the exercise group were given access to a running wheel and Nx treated mice were fed 600 mg/kg pelleted into their chow. Mice were scarified at weeks 4, 8, 12 and 20 weeks. Mice were monitored weekly for tumor development, activity and food consumption. Efficacy of exercise and Nexrutine was determined by histopathological evaluation of the prostate and tissue expression of pAkt and p65, key signaling proteins for carcinogenesis. One-way analysis of variance was performed with significance set at p<0.05. RESULTS: No significant pathological changes were observed as a function of time, therefore, data were pooled for analysis. Animals on exercise intervention group ran an average of 4.4 km/day. Both exercise and Nx groups presented with palpable tumors 4 weeks later than the control group. While 100% of animals developed tumors (varying stages), Nx treated and exercising TRAMP mice had fewer poorly differentiated tumors compared to controls (p<0.05). Only Nexrutine expressed lower pAkt in tumors. No differences were seen in p65 expression. CONCLUSIONS: Our data provides preliminary evidence that Nx can act as an exercise mimetic in protecting against tumor development in prostate cancer. Though both Nx and exercise decreased advanced stage tumors, only Nx has lower pAkt expression. Therefore, continued efforts need to be made to decipher the mechanisms by which exercise reduces tumors development.