Potential Otubain1 Inhibitor, an Approach for a Treatment againstBreast Cancer

Document Type : Original Article

Authors
Andrea Muñoz-Ayala
Victor G. García-González
Angel Pulido-Capiz
Brenda Chimal-Vega
Ruth A. García-Villarreal
José L. Vique-Sánchez
School of Medicine Campus Mexicali, Autonomous University of Baja California, Mexicali, 21000, BC, México.
10.22088/IJMCM.BUMS.13.4.350
Abstract
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