Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines

• Published in: Antioxidants 2024-11, Vol.13 (11), p.1340
• Main Authors: Hussein, Mohamed A F, Lismont, Celien, Costa, Cláudio F, Li, Hongli, Claessens, Frank, Fransen, Marc
• Format: Article
• Language: English
• Subjects: androgen receptor; Androgen receptors; Androgens; Biosynthesis; catalase; Cell activation; Cell proliferation; Cell survival; Cellular stress response; Coenzyme A; Development and progression; Enzymes; Fatty acids; Health aspects; Homeostasis; Hydrogen peroxide; Kinases; Ligands; Metabolism; Metastasis; Oxidation; Oxidation-reduction reaction; Peptides; Peroxisomes; Physiological aspects; Physiology; Prostate cancer; Protein turnover; Proteins; Proteomes; Proteomics; R1881; RNA-mediated interference; Tumor cell lines
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox13111340

Prostate cancer (PCa) is associated with disruptions in cellular redox balance. Given the intricate role of peroxisomes in redox metabolism, we conducted comprehensive proteomics analyses to compare peroxisomal and redox protein profiles between benign (RWPE-1) and malignant (22Rv1, LNCaP, and PC3) prostate cell lines. Our analyses revealed significant enrichment of the "peroxisome" pathway among proteins notably upregulated in androgen receptor (AR)-positive cell lines. In addition, catalase (CAT) activity was consistently higher in these malignant cell lines compared to RWPE-1, which contrasts with previous studies reporting lower CAT levels and increased H O levels in PCa tissues compared to adjacent normal tissues. To mimic this clinical scenario, we used RNA interference to knock down CAT expression. Our results show that reduced CAT levels enhanced 22Rv1 and LNCaP cell proliferation. R1881-induced activation of AR, a key driver of PCa, increased expression of the H O -producing peroxisomal β-oxidation enzymes acyl-coenzyme A oxidase 1 and 3, reduced CAT expression and activity, and elevated peroxisomal H O levels. Considering these changes and other antioxidant enzyme profile alterations, we propose that enhanced AR activity in PCa reduces CAT function, leading to increased peroxisomal H O levels that trigger adaptive stress responses to promote cell survival, growth, and proliferation.