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

Autor: Cimona V. Hinton, Gabrielle Edwards, Nathan J. Bowen, Ohuod Hawsawi, Alira Danaher, Guangdi Wang, Qiang Zhang, Liza J. Burton, Kia J. Jones, Valerie Odero-Marah, Jodi Dougan, Peri Nagappan, Jin Zou
Rok vydání: 2019
Předmět:
Male
Proteomics
0301 basic medicine
medicine.disease_cause
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Prostate
Cell Line
Tumor
medicine
Metabolome
Humans
Metabolomics
oxidative stress
Viability assay
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Peroxidase
chemistry.chemical_classification
Extracellular Matrix Proteins
Reactive oxygen species
Gene knockdown
Chemistry
Organic Chemistry
Gluconeogenesis
apoptosis
Prostatic Neoplasms
General Medicine
PXDN
prostate cancer
medicine.disease
3. Good health
Computer Science Applications
030104 developmental biology
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
Apoptosis
030220 oncology & carcinogenesis
Cancer research
metabolome
Oxidative stress
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 12
International Journal of Molecular Sciences, Vol 20, Iss 12, p 3046 (2019)
ISSN: 1422-0067
DOI: 10.3390/ijms20123046
Popis: 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.
Databáze: OpenAIRE
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