Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines
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)...
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MDPI AG
2024-11-01
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| Series: | Antioxidants |
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| author | Mohamed A. F. Hussein Celien Lismont Cláudio F. Costa Hongli Li Frank Claessens Marc Fransen |
| author_facet | Mohamed A. F. Hussein Celien Lismont Cláudio F. Costa Hongli Li Frank Claessens Marc Fransen |
| author_sort | Mohamed A. F. Hussein |
| collection | DOAJ |
| description | 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<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub>-producing peroxisomal β-oxidation enzymes acyl-coenzyme A oxidase 1 and 3, reduced CAT expression and activity, and elevated peroxisomal H<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> levels that trigger adaptive stress responses to promote cell survival, growth, and proliferation. |
| format | Article |
| id | doaj-art-729430ecba074906a6d69bc853b8b83c |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-729430ecba074906a6d69bc853b8b83c2025-08-20T02:26:45ZengMDPI AGAntioxidants2076-39212024-11-011311134010.3390/antiox13111340Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell LinesMohamed A. F. Hussein0Celien Lismont1Cláudio F. Costa2Hongli Li3Frank Claessens4Marc Fransen5Laboratory of Peroxisome Biology and Intracellular Communication, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, BelgiumLaboratory of Peroxisome Biology and Intracellular Communication, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, BelgiumLaboratory of Peroxisome Biology and Intracellular Communication, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, BelgiumLaboratory of Peroxisome Biology and Intracellular Communication, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, BelgiumLaboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, BelgiumLaboratory of Peroxisome Biology and Intracellular Communication, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, BelgiumProstate 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<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub>-producing peroxisomal β-oxidation enzymes acyl-coenzyme A oxidase 1 and 3, reduced CAT expression and activity, and elevated peroxisomal H<sub>2</sub>O<sub>2</sub> 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<sub>2</sub>O<sub>2</sub> levels that trigger adaptive stress responses to promote cell survival, growth, and proliferation.https://www.mdpi.com/2076-3921/13/11/1340peroxisomesprostate cancercatalasehydrogen peroxideandrogen receptorR1881 |
| spellingShingle | Mohamed A. F. Hussein Celien Lismont Cláudio F. Costa Hongli Li Frank Claessens Marc Fransen Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines Antioxidants peroxisomes prostate cancer catalase hydrogen peroxide androgen receptor R1881 |
| title | Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines |
| title_full | Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines |
| title_fullStr | Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines |
| title_full_unstemmed | Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines |
| title_short | Characterization of the Peroxisomal Proteome and Redox Balance in Human Prostate Cancer Cell Lines |
| title_sort | characterization of the peroxisomal proteome and redox balance in human prostate cancer cell lines |
| topic | peroxisomes prostate cancer catalase hydrogen peroxide androgen receptor R1881 |
| url | https://www.mdpi.com/2076-3921/13/11/1340 |
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