Demir Ummuhan, Erdogdu Rabia
Department of Molecular Biology and Genetics, Istanbul Medeniyet University Faculty of Engineering and Natural Sciences, Istanbul, Türkiye.
Science and Advanced Technologies Research Center (BILTAM), Istanbul Medeniyet University, Istanbul, Türkiye.
Urol Res Pract. 2025 May 21;51(1):33-37. doi: 10.5152/tud.2025.24115.
Objective: Posttranslational protein modifications are crucial for fine-tuning protein function. NSC632839 is a dual deubiquitination and desumoylation inhibitor. The desumoylation enzyme SENP2 is one of the targets of NSC632839. This study aimed to evaluate NSC632839 as an antiproliferative agent in prostate cancer (PCa). Methods: The IC50 values for NSC632839 were determined in PCa cell lines PC3 and LNCaP and normal fibroblast cells CCD-1072Sk by crystal violet staining. The colony- formation ability of PC3 and LNCaP cells upon NSC632839 treatment was evaluated by a 2D colony-formation assay. The expression level of SENP2 and its correlation with androgen receptor (AR) were investigated in PCa tissue samples using publicly avail- able datasets. Results: The IC50 values of NSC632839 were 3.1, 1.9, and 17.7 for LNCaP, PC3, and CCD- 1072Sk, respectively. In this IC50 concentration, NSC632839 completely abolished the colony-formation ability of PC3 cells. The expression level of SENP2 was elevated in metastatic PCa tissue samples and was correlated with the AR. Conclusion: NSC632839 was an antiproliferative agent in PCa cells at low doses. Therefore, NSC632839 is a strong drug candidate requiring further studies.
蛋白质翻译后修饰对于精确调节蛋白质功能至关重要。NSC632839是一种双去泛素化和去SUMO化抑制剂。去SUMO化酶SENP2是NSC632839的靶点之一。本研究旨在评估NSC632839作为前列腺癌（PCa）抗增殖剂的作用。方法：通过结晶紫染色法测定NSC632839在PCa细胞系PC3和LNCaP以及正常成纤维细胞CCD - 1072Sk中的IC50值。通过二维集落形成试验评估NSC632839处理后PC3和LNCaP细胞的集落形成能力。利用公开可用数据集在PCa组织样本中研究SENP2的表达水平及其与雄激素受体（AR）的相关性。结果：NSC632839对LNCaP、PC3和CCD - 1072Sk的IC50值分别为3.1、1.9和17.7。在该IC50浓度下，NSC632839完全消除了PC3细胞的集落形成能力。转移性PCa组织样本中SENP2的表达水平升高，且与AR相关。结论：低剂量时NSC632839是PCa细胞中的抗增殖剂。因此，NSC632839是一个值得进一步研究的强有力的候选药物。
