Targeting Prostate Cancer Cells by an Isopeptidase Inhibitor NSC632839.

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.