Exercise and Phellodendron amurense extract differentially impinge on oxidative stress response pathways in a mouse model of prostate cancer.

Abstract

Prostate cancer is the most common non-cutaneous cancer in men in the United States. Oxidative stress, induced by chronic prostatic inflammation, impairs normal protective mechanisms in the prostate and increases the risk for cancer progression. We reported that Phellodendron amurense extract (Nexrutine) had similar effects as exercise in reducing highly aggressive tumors in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Here, we examined changes in the transcriptome to understand how these two interventions affect prostate cancer. Twenty-four, 8-10 weeks old male TRAMP mice, were randomized to control, exercise, and Phellodendron amurense extract intervention. At the end of the study, prostate tumors were excised, weighed, and processed for immunohistochemistry and transcriptome analysis. Changes in gene expression (&#x2265;&#x2009;1.5-fold change, adjusted p&#x2009;<&#x2009;0.05), gene ontology and pathway analyses were carried out. No significant difference was observed in body or genitourinary weight between groups. There was differential response to interventions with greater percentage of high-grade tumors in the control group. Triglyceride, metabolic processes and localization, transport processes were affected by exercise and Phellodendron amurense extract, respectively. At the transcriptome level, our results suggest that both interventions differentially affect pathways that allow them to overcome high oxidative stress threshold and protect against high-grade tumors.