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

Authors
Park, MinaHwang, Jee WonCho, YenaKim, SaegunHan, Sang HoonYu, JinsuhHa, SojungKim, Woo-YoungKim, Su-NamKim, In SuKim, Yong Kee
Issue Date
2021-05
Publisher
Nature Publishing Group
Citation
Scientific Reports, v.11, no.1
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.
Keywords
CHROMOSOMAL PASSENGER COMPLEX; P-GLYCOPROTEIN; AURORA-B; MECHANISMS; TUBULIN; CHROMONES; DISCOVERY; SCAFFOLD; CPC
ISSN
2045-2322
URI
https://pubs.kist.re.kr/handle/201004/117037
DOI
10.1038/s41598-021-90337-w
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KIST Article > 2021
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