loading page

5-(N-methylmaleimid-3-yl)-chromone, a novel microtubule inhibitor, exerts anti-proliferative effects in MDR cancer cells and cancer stem cells
  • +7
  • Mina Park,
  • Jee Won Hwang,
  • Yena Cho,
  • Saegun Kim,
  • Sang Hoon Han,
  • Jinsuh Yu,
  • Woo-Young Kim,
  • Su-Nam Kim,
  • In Su Kim,
  • Yong Kee Kim
Mina Park
Sookmyung Women's University
Author Profile
Jee Won Hwang
Sookmyung Women's University
Author Profile
Yena Cho
Sookmyung Women's University
Author Profile
Saegun Kim
Sungkyunkwan University
Author Profile
Sang Hoon Han
Sungkyunkwan University
Author Profile
Jinsuh Yu
Sookmyung Women's University
Author Profile
Woo-Young Kim
Sookmyung Women's University
Author Profile
Su-Nam Kim
Korea Institute of Science and Technology
Author Profile
In Su Kim
Sungkyunkwan University
Author Profile
Yong Kee Kim
Sookmyung Women's University
Author Profile

Abstract

Background and Purpose: 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. Experimental Approach: Key Results: 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. Conclusion and Implications: 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.