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

• Published in: Scientific reports Vol. 11; no. 1; p. 10822
• Main 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.05.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/154; 631/67/1059/2326; 631/67/71; 631/80/128/1653; 631/80/641/1656; Antineoplastic drugs; Antitumor agents; Cancer; Cancer therapies; Cell cycle; Chemotherapy; Cyclin B; Drug development; Flow cytometry; Humanities and Social Sciences; multidisciplinary; Multidrug resistance; Multidrug resistant organisms; P-Glycoprotein; Science; Science (multidisciplinary); Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-90337-w

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.