A novel M phase blocker, DCZ3301 enhances the sensitivity of bortezomib in resistant multiple myeloma through DNA damage and mitotic catastrophe.

ABSTRACT:

Background

DCZ3301, a novel aryl-guanidino compound previously reported by our group, exerts cytotoxic effects against multiple myeloma (MM), diffused large B cell lymphoma (DLBCL), and T-cell leukemia/lymphoma. However, the underlying mechanism of its action remains unknown.

Methods

We generated bortezomib (BTZ)-resistant cell lines, treated them with various concentrations of DCZ3301 over varying periods, and studied its effect on colony formation, cell proliferation, apoptosis, cell cycle, DNA synthesis, and DNA damage response. We validated our results using in vitro and in vivo experimental models.

Results

DCZ3301 overcame bortezomib (BTZ) resistance through regulation of the G₂/M checkpoint in multiple myeloma (MM) in vitro and in vivo. Furthermore, t

SUBMITTER: Hu L 

PROVIDER: S-EPMC7285565 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature