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

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...

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Autores principales: Mina Park, Jee Won Hwang, Yena Cho, Saegun Kim, Sang Hoon Han, Jinsuh Yu, Sojung Ha, Woo-Young Kim, Su-Nam Kim, In Su Kim, Yong Kee Kim
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Science
Q
Acceso en línea:https://doaj.org/article/4f6767626ab44f6081ed33688afadd49
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spelling oai:doaj.org-article:4f6767626ab44f6081ed33688afadd492021-12-02T14:42:20ZA novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells10.1038/s41598-021-90337-w2045-2322https://doaj.org/article/4f6767626ab44f6081ed33688afadd492021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90337-whttps://doaj.org/toc/2045-2322Abstract 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.Mina ParkJee Won HwangYena ChoSaegun KimSang Hoon HanJinsuh YuSojung HaWoo-Young KimSu-Nam KimIn Su KimYong Kee KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mina Park
Jee Won Hwang
Yena Cho
Saegun Kim
Sang Hoon Han
Jinsuh Yu
Sojung Ha
Woo-Young Kim
Su-Nam Kim
In Su Kim
Yong Kee Kim
A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
description 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.
format article
author Mina Park
Jee Won Hwang
Yena Cho
Saegun Kim
Sang Hoon Han
Jinsuh Yu
Sojung Ha
Woo-Young Kim
Su-Nam Kim
In Su Kim
Yong Kee Kim
author_facet Mina Park
Jee Won Hwang
Yena Cho
Saegun Kim
Sang Hoon Han
Jinsuh Yu
Sojung Ha
Woo-Young Kim
Su-Nam Kim
In Su Kim
Yong Kee Kim
author_sort Mina Park
title A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
title_short A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
title_full A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
title_fullStr A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
title_full_unstemmed A novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
title_sort novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cells
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/4f6767626ab44f6081ed33688afadd49
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