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Muñoz-Ayala A, García-González V G, Pulido-Capiz A, Chimal-Vega B, García-Villarreal R, Vique-sanchez J L. Potential Otubain1 Inhibitor, an Approach for a Treatment against Breast Cancer. Int J Mol Cell Med 2024;
URL: http://ijmcmed.org/article-1-2397-en.html
Potential Otubain1 Inhibitor, an Approach for a Treatment against Breast Cancer
Andrea Muñoz-Ayala1 , Victor G. García-González1 , Angel Pulido-Capiz1 , Brenda Chimal-Vega1 , Ruth García-Villarreal1 , Jose luis Vique-sanchez 2
1- School of Medicine Campus Mexicali, Autonomous University of Baja California, Mexicali, 21000, BC, México.
2- School of Medicine Campus Mexicali, Autonomous University of Baja California, Mexicali, 21000, BC, México. , jvique@uabc.edu.mx
Abstract:   (42 Views)
The develop of new anticancer drug continues worldwide and one of the new therapeutic targets to reach it is Otubain 1 (OTUB1), since OTUB1 has functions related to prognosis in a variety of tumors and is strongly related to tumor proliferation, migration, and apoptosis by their functions on deubiquitinating. This study uses OTUB1´s active site to develop a specific pharmacological treatment to regulate the OTUB1 functions. The aim of this research was to evaluate the effects of ten compounds (OT1 - OT10), that previously were selected by molecular docking to develop a new anticancer drug to decrease the OTUB1 functions in the cancer processes. We evaluated the cytotoxic effect of OT1 – OT10 compounds on MCF-7, BT474 and MDA-MB 231 cells by MTT assay, and we determined characteristics of apoptosis by western blot analysis. Then, the best compound (OT5) was analyzed by molecular docking, molecular dynamics and theoretical toxicity for describing the interactions of OT5 compound with the OTUB1´s active site. We proposed that the OT5 compound has a high probability to be selective against OTUB1, with an apoptosis (regulating caspase-8) and cytotoxic effect on some cancer lines; IC50 for MCF-7: 97 µM and MDA-MB 231:147 µM, as well as we described that this compound could have specific interactions in the catalytic domain of OTUB1, modifying this protein’s activity, decreasing the OTUB1 functions, and probably safe for humans. These results show the high potential of this compound for promoting the development of this compound as a new drug against cancer.
Keywords: Apoptosis, caspase-8, MCF-7, MDA-MB 231, drug
Full-Text [PDF 578 kb]   (19 Downloads)    
Type of Study: Original Article | Subject: Cancer
Received: 2024/07/29 | Accepted: 2024/09/8 | Published: 2024/11/13
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