Title

Proteomics-Metabolomics Combined Approach Identifies Peroxidasin as a Protector Against Metabolic and Oxidative Stress in Prostate Cancer.

Funding Source

National Institutes of Health, National Cancer Institute

Grant Number

G12MD007590,P20MD002285-01, P30CA036727

Department

Department of Chemistry

Document Type

Article

Publication Date

6-2-2019

Abstract

Peroxidasin (PXDN), a human homolog of Drosophila PXDN, belongs to the family of heme peroxidases and has been found to promote oxidative stress in cardiovascular tissue, however, its role in prostate cancer has not been previously elucidated. We hypothesized that PXDN promotes prostate cancer progression via regulation of metabolic and oxidative stress pathways. We analyzed PXDN expression in prostate tissue by immunohistochemistry and found increased PXDN expression with prostate cancer progression as compared to normal tissue or cells. PXDN knockdown followed by proteomic analysis revealed an increase in oxidative stress, mitochondrial dysfunction and gluconeogenesis pathways. Additionally, Liquid Chromatography with tandem mass spectrometry (LC-MS/MS)-based metabolomics confirmed that PXDN knockdown induced global reprogramming associated with increased oxidative stress and decreased nucleotide biosynthesis. We further demonstrated that PXDN knockdown led to an increase in reactive oxygen species (ROS) associated with decreased cell viability and increased apoptosis. Finally, PXDN knockdown decreased colony formation on soft agar. Overall, the data suggest that PXDN promotes progression of prostate cancer by regulating the metabolome, more specifically, by inhibiting oxidative stress leading to decreased apoptosis. Therefore, PXDN may be a biomarker associated with prostate cancer and a potential therapeutic target.

Comments

DOI: 10.3390/ijms20123046

PubMed ID: 31234468

Funding text

Funding: This work was supported by NIH grants P20MD002285-01 (VOM), G12MD007590, and the Fred & Pamela Buffett Cancer Center Support Grant (P30CA036727, NCI) for the metabolomics resources at UNMC.

Share

COinS