Unknown

Dataset Information

0

A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells.


ABSTRACT: The success of cancer chemotherapy is limited by multidrug resistance (MDR), which is mainly caused by P-glycoprotein (P-gp) overexpression. In the present study, we describe a novel microtubule inhibitor, 5-(N-methylmaleimid-3-yl)-chromone (SPC-160002), that can be used to overcome MDR. A synthetic chromone derivative, SPC-160002, showed a broad spectrum of anti-proliferative effects on various human cancer cells without affecting P-gp expression and its drug efflux function. Treatment with SPC-160002 arrested the cell cycle at the M phase, as evidenced using fluorescence-activated cell sorting analysis, and increased the levels of mitotic marker proteins, including cyclin B, pS10-H3, and chromosomal passenger complex. This mitotic arrest by SPC-160002 was mediated by promoting and stabilizing microtubule polymerization, similar to the mechanism observed in case of taxane-based drugs. Furthermore, SPC-160002 suppressed the growth and sphere-forming activity of cancer stem cells. Our data herein strongly suggest that SPC-160002, a novel microtubule inhibitor, can be used to overcome MDR and can serve as an attractive candidate for anticancer drugs.

SUBMITTER: Park M 

PROVIDER: S-EPMC8144389 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC8209271 | biostudies-literature
| S-EPMC2742177 | biostudies-literature
| S-EPMC4366620 | biostudies-literature
| S-EPMC8132113 | biostudies-literature
| S-EPMC6173468 | biostudies-literature
| S-EPMC9265127 | biostudies-literature
| S-EPMC10506422 | biostudies-literature
| S-EPMC5962668 | biostudies-literature
| S-EPMC7925909 | biostudies-literature
| S-EPMC7181169 | biostudies-literature