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Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance
The overexpression of ATP-binding cassette (ABC) transporters is the main cause of cancer multidrug resistance (MDR), which leads to chemotherapy failure. Uncaria alkaloids are the major active components isolated from uncaria, which is a common Chinese herbal medicine. In this study, the MDR-revers...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467778/ https://www.ncbi.nlm.nih.gov/pubmed/28534954 http://dx.doi.org/10.3892/ijo.2017.4005 |
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author | Huang, Bao-Yuan Zeng, Yu Li, Ying-Jie Huang, Xiao-Jun Hu, Nan Yao, Nan Chen, Min-Feng Yang, Zai-Gang Chen, Zhe-Sheng Zhang, Dong-Mei Zeng, Chang-Qing |
author_facet | Huang, Bao-Yuan Zeng, Yu Li, Ying-Jie Huang, Xiao-Jun Hu, Nan Yao, Nan Chen, Min-Feng Yang, Zai-Gang Chen, Zhe-Sheng Zhang, Dong-Mei Zeng, Chang-Qing |
author_sort | Huang, Bao-Yuan |
collection | PubMed |
description | The overexpression of ATP-binding cassette (ABC) transporters is the main cause of cancer multidrug resistance (MDR), which leads to chemotherapy failure. Uncaria alkaloids are the major active components isolated from uncaria, which is a common Chinese herbal medicine. In this study, the MDR-reversal activities of uncaria alkaloids, including rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine (Icory), hirsutine and hirsuteine, were screened; they all exhibited potent reversal efficacy when combined with doxorubicin. Among them, Icory significantly sensitized ABCB1-overexpressing HepG2/ADM and MCF-7/ADR cells to vincristine, doxorubicin and paclitaxel, but not to the non-ABCB1 substrate cisplatin. Noteworthy, Icory selectively reversed ABCB1-overexpressing MDR cancer cells but not ABCC1- or ABCG2-mediated MDR. Further mechanistic study revealed that Icory increased the intracellular accumulation of doxorubicin in ABCB1-overexpressing cells by blocking the efflux function of ABCB1. Instead of inhibiting ABCB1 expression and localization, Icory acts as a substrate of the ABCB1 transporter by competitively binding to substrate binding sites. Collectively, these results indicated that Icory reversed ABCB1-mediated MDR by suppressing its efflux function, and it would be beneficial to increase the efficacy of these types of uncaria alkaloids and develop them to be selective ABCB1-mediated MDR-reversal agents. |
format | Online Article Text |
id | pubmed-5467778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-54677782017-06-16 Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance Huang, Bao-Yuan Zeng, Yu Li, Ying-Jie Huang, Xiao-Jun Hu, Nan Yao, Nan Chen, Min-Feng Yang, Zai-Gang Chen, Zhe-Sheng Zhang, Dong-Mei Zeng, Chang-Qing Int J Oncol Articles The overexpression of ATP-binding cassette (ABC) transporters is the main cause of cancer multidrug resistance (MDR), which leads to chemotherapy failure. Uncaria alkaloids are the major active components isolated from uncaria, which is a common Chinese herbal medicine. In this study, the MDR-reversal activities of uncaria alkaloids, including rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine (Icory), hirsutine and hirsuteine, were screened; they all exhibited potent reversal efficacy when combined with doxorubicin. Among them, Icory significantly sensitized ABCB1-overexpressing HepG2/ADM and MCF-7/ADR cells to vincristine, doxorubicin and paclitaxel, but not to the non-ABCB1 substrate cisplatin. Noteworthy, Icory selectively reversed ABCB1-overexpressing MDR cancer cells but not ABCC1- or ABCG2-mediated MDR. Further mechanistic study revealed that Icory increased the intracellular accumulation of doxorubicin in ABCB1-overexpressing cells by blocking the efflux function of ABCB1. Instead of inhibiting ABCB1 expression and localization, Icory acts as a substrate of the ABCB1 transporter by competitively binding to substrate binding sites. Collectively, these results indicated that Icory reversed ABCB1-mediated MDR by suppressing its efflux function, and it would be beneficial to increase the efficacy of these types of uncaria alkaloids and develop them to be selective ABCB1-mediated MDR-reversal agents. D.A. Spandidos 2017-05-17 /pmc/articles/PMC5467778/ /pubmed/28534954 http://dx.doi.org/10.3892/ijo.2017.4005 Text en Copyright © 2017, Spandidos Publications |
spellingShingle | Articles Huang, Bao-Yuan Zeng, Yu Li, Ying-Jie Huang, Xiao-Jun Hu, Nan Yao, Nan Chen, Min-Feng Yang, Zai-Gang Chen, Zhe-Sheng Zhang, Dong-Mei Zeng, Chang-Qing Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance |
title | Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance |
title_full | Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance |
title_fullStr | Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance |
title_full_unstemmed | Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance |
title_short | Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance |
title_sort | uncaria alkaloids reverse abcb1-mediated cancer multidrug resistance |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5467778/ https://www.ncbi.nlm.nih.gov/pubmed/28534954 http://dx.doi.org/10.3892/ijo.2017.4005 |
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