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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-90337-w |
| _version_ | 1819040258096889856 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T09:06:14Z |
| format | Article |
| id | doaj.art-4f6767626ab44f6081ed33688afadd49 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-21T09:06:14Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-4f6767626ab44f6081ed33688afadd492022-12-21T19:09:21ZengNature PortfolioScientific Reports2045-23222021-05-0111111110.1038/s41598-021-90337-wA novel synthetic microtubule inhibitor exerts antiproliferative effects in multidrug resistant cancer cells and cancer stem cellsMina Park0Jee Won Hwang1Yena Cho2Saegun Kim3Sang Hoon Han4Jinsuh Yu5Sojung Ha6Woo-Young Kim7Su-Nam Kim8In Su Kim9Yong Kee Kim10Research Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversityResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversityResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversitySchool of Pharmacy, Sungkyunkwan UniversitySchool of Pharmacy, Sungkyunkwan UniversityResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversityResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversityResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversityNatural Product Research Institute, Korea Institute of Science and TechnologySchool of Pharmacy, Sungkyunkwan UniversityResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Sookmyung Women’s UniversityAbstract 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.https://doi.org/10.1038/s41598-021-90337-w |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-90337-w |
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