Characterization of a recently synthesized microtubule-targeting compound that disrupts mitotic spindle poles in human cells.

ABSTRACT: We reveal the effects of a new microtubule-destabilizing compound in human cells. C75 has a core thienoisoquinoline scaffold with several functional groups amenable to modification. Previously we found that sub micromolar concentrations of C75 caused cytotoxicity. We also found that C75 inhibited microtubule polymerization and competed with colchicine for tubulin-binding in vitro. However, here we found that the two compounds synergized suggesting differences in their mechanism of action. Indeed, live imaging revealed that C75 causes different spindle phenotypes compared to colchicine. Spindles remained bipolar and collapsed after colchicine treatment, while C75 caused bipolar spindles to become multipolar. Importantly, microtubules rapidly disappeared after C75-treatment, but then grew ba

SUBMITTER: Jaunky DB 

PROVIDER: S-EPMC8655040 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature