Nexrutine and exercise similarly prevent high grade prostate tumors in transgenic mouse model

Abstract

The purpose of this investigation was to compare the antitumorigenic effects of the natural product Nexrutine to voluntary wheel running (VWR) in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Forty-five, 10-week old TRAMP mice were randomized to either receive free access to the running wheel, Nexrutine pelleted into chow at 600 mg/kg or no treatment control. Mice were serially sacrificed at weeks 4, 8,12 and 20 weeks. Palpable tumors, body weight, food consumption and running wheel activity were monitored weekly. At necropsy, tumors and serum were harvested and stored for analysis. Serum was used to quantify circulating cytokines in 4 and 20 week time points. Nexrutine supplementation led to a 66% protection against high grade tumors. Exercise resulted in a 60% protection against high grade tumors. Both interventions reduced concentrations of IL-1α. Exercise also significantly lowered concentrations of eotaxin, IL-5, IL-12(p40) and VEGF. While there were no significant differences at baseline, exercise mice had significantly lower IL-5 and VEGF compared to control at the 20 week time point. Nexrutine also significantly reduced circulating IL-9 concentrations. No significant differences were observed when compared to the control group. Immunohistochemistry of tumor sections showed significantly lower expression of pAkt in Nexrutine fed mice with no visible differences for NFκB. In conclusion, both Nexrutine and exercise suppressed tumor growth. Though similar outcomes were seen in this comparative effectiveness study, the mechanisms by which exercise and Nexrutine exert this benefit may focus on different pathways.

Pilot Study on the Impact of a Home-Based Exercise Program on Inflammatory Cytokines and Quality of Life in Men with Prostate Cancer Under Active Surveillance

“…Despite challenges of COVID-19 restrictions, 9 participants in the intervention group and 6 participants in the control group completed the study. Although not statistically significant, a decrease across all biomarkers followed the same trend previously seen in the murine exercise study in our laboratory, 34 lending support for the translational nature of our intervention to the clinical population. Our results are similar to findings of a home-based exercise intervention by Hvid et al 24 who observed a non-statistically significant decrease in mean IL-6 after 24 months; however, this study found an increase TNF-α within the same time parameters.…”

“…2,10,11 Work within our laboratory has demonstrated shifts in circulating cytokines in response to exercise in preclinical studies. (34) 12 Specifically, our group noted that up to 20 weeks of voluntary wheel running significantly reduced the progression to high-risk tumors in transgenic prostate tumor challenged mouse models. This reduction in tumor progression was associated with significant decreases in pro-inflammatory cytokines, such as eotaxin, interleukin (IL)-1a, IL-5, IL-12 (p40) and VEGF.…”

Therapeutic yoga reduces pro-tumorigenic cytokines in cancer survivors

“…IFN-γ has been found in different studies to have protective effects on tumor growth and suggestive of a strong immune response [ 41 ]. Specifically, low serum IFN-γ levels have been inversely associated with tumor stage [ 42 ] and tumor size [ 43 ] though the specific mechanism attributed to this benefit is still unknown.…”

Voluntary Wheel Running Does Not Enhance Radiotherapy Efficiency in a Preclinical Model of Prostate Cancer: The Importance of Physical Activity Modalities?

“…Nevertheless, there are large disparities between studies, with some reporting no effect or even increased tumor growth in response to physical activity. In PCa more specifically, some studies reported slower tumor growth with physical activity [ 10 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ], while others found no effect [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. McCullough et al even reported that while TR had no effect on tumor weight in immunocompetent Copenhagen rats, it significantly increased tumor weight in nude rats [ 28 ].…”