A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
- Authors
- Park, Mina; Hwang, Jee Won; Cho, Yena; Kim, Saegun; Han, Sang Hoon; Yu, Jinsuh; Ha, Sojung; Kim, Woo-Young; Kim, Su-Nam; Kim, In Su; Kim, Yong Kee
- Issue Date
- May-2021
- Publisher
- NATURE RESEARCH
- Citation
- SCIENTIFIC REPORTS, v.11, no.1, pp 1 - 11
- Pages
- 11
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 11
- Number
- 1
- Start Page
- 1
- End Page
- 11
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/146625
- DOI
- 10.1038/s41598-021-90337-w
- ISSN
- 2045-2322
- 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.
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