Hussein Mohamed A F, Lismont Celien, Costa Cláudio F, Li Hongli, Claessens Frank, Fransen Marc
Laboratory of Peroxisome Biology and Intracellular Communication, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
Department of Biochemistry, Faculty of Pharmacy, Assiut University, Asyut 71515, Egypt.
Antioxidants (Basel). 2024 Nov 1;13(11):1340. 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 HO 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 HO-producing peroxisomal β-oxidation enzymes acyl-coenzyme A oxidase 1 and 3, reduced CAT expression and activity, and elevated peroxisomal HO 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 HO levels that trigger adaptive stress responses to promote cell survival, growth, and proliferation.
前列腺癌（PCa）与细胞氧化还原平衡的破坏有关。鉴于过氧化物酶体在氧化还原代谢中所起的复杂作用，我们进行了全面的蛋白质组学分析，以比较良性（RWPE-1）和恶性（22Rv1、LNCaP和PC3）前列腺细胞系之间的过氧化物酶体和氧化还原蛋白谱。我们的分析表明，在雄激素受体（AR）阳性细胞系中显著上调的蛋白质中，“过氧化物酶体”途径显著富集。此外，与RWPE-1相比，这些恶性细胞系中的过氧化氢酶（CAT）活性始终较高，这与之前的研究结果相反，之前的研究报告称，与相邻正常组织相比，PCa组织中的CAT水平较低，HO水平升高。为了模拟这种临床情况，我们使用RNA干扰来敲低CAT的表达。我们的结果表明，CAT水平降低会增强22Rv1和LNCaP细胞的增殖。R1881诱导的AR激活是PCa的关键驱动因素，它增加了产生HO的过氧化物酶体β-氧化酶酰基辅酶A氧化酶1和3的表达，降低了CAT的表达和活性，并提高了过氧化物酶体HO水平。考虑到这些变化以及其他抗氧化酶谱的改变，我们提出PCa中增强的AR活性会降低CAT功能，导致过氧化物酶体HO水平升高，从而引发适应性应激反应，以促进细胞存活、生长和增殖。
