Potential Otubain 1 (OTUB1) Ligand, Advances for a Treatment Against Prostate Cancer

Advances in developing new anticancer drugs continue, and one of the new therapeutic targets to reach is Otubain 1 (OTUB1) because OTUB1 has functions related to prognosis in a variety of tumors, and this protein is strongly related to tumor proliferation, migration, and apoptosis by its deubiquitinating function. This study evaluated a potential OTUB1 ligand, the OT3 compound, which our research group previously proposed as a compound directed to interact with OTUB1´s active site to develop a drug to regulate OTUB1´s functions. The aim of this research is to evaluate the effects of the OT3 compound on OTUB1´s functions in prostate cancer (PC3) by in vitro cultures. We determined the cytotoxic effect of the OT3 compound on PC3 cells by MTT assays and examined the regulation of p-FAK and Caspase-3, which are involved in decreasing the viability of the cultures and regulating apoptosis, as determined by western blot analysis. Then, the OT3 compound was analyzed using molecular dynamics to describe the interactions of the OT3 compound with OTUB1´s active site. We propose that the OT3 compound has a high probability of being selective against OTUB1, with apoptosis (regulating caspase-3) and cytotoxic effect on prostate cancer lines; IC50 140 µM, as well as we describe that this compound could have specific interactions in the OTUB1´s active site, decreasing the OTUB1 functions, and is probably safe for humans. These results show the high potential of this compound as a new drug against prostate cancer.