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Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells

[Image: see text] In this study, we established a simple and rapid in vitro method for screening multidrug resistance (MDR) reversal agents in traditional Chinese medicines (TCMs), which could better correspond to the MDR reversing effect in vivo. Here, D-luciferin, a substrate for the enzyme firefl...

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Autores principales: Zhao, Yue, Tang, Chaoyuan, Huang, Jingyi, Zhang, Hongyan, Shi, Jingbin, Xu, Shujun, Ma, Lisha, Peng, Chun, Liu, Qi, Xiong, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909823/
https://www.ncbi.nlm.nih.gov/pubmed/36777569
http://dx.doi.org/10.1021/acsomega.2c07096
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author Zhao, Yue
Tang, Chaoyuan
Huang, Jingyi
Zhang, Hongyan
Shi, Jingbin
Xu, Shujun
Ma, Lisha
Peng, Chun
Liu, Qi
Xiong, Yang
author_facet Zhao, Yue
Tang, Chaoyuan
Huang, Jingyi
Zhang, Hongyan
Shi, Jingbin
Xu, Shujun
Ma, Lisha
Peng, Chun
Liu, Qi
Xiong, Yang
author_sort Zhao, Yue
collection PubMed
description [Image: see text] In this study, we established a simple and rapid in vitro method for screening multidrug resistance (MDR) reversal agents in traditional Chinese medicines (TCMs), which could better correspond to the MDR reversing effect in vivo. Here, D-luciferin, a substrate for the enzyme firefly luciferase and also a substrate for ATP-binding cassette transporters (ABC transporters), was used as the probe to detect its efflux kinetics caused by ABC transporters. First, we established a stable doxorubicin (DOX)-resistant cell line (MCF-7/DOX(Fluc)) that overexpressed luciferase. Then, some kinds of TCMs were chosen for the MDR reversal agents to measure its effect on inhibiting the D-luciferin outflow from MCF-7/DOX(Fluc), and the ideal reversal agent with the least D-luciferin efflux from MCF-7/DOX(Fluc) was selected to further investigate its effect combined with DOX on MCF-7/DOX(Fluc) tumor-bearing mice. The results indicated that quercetin (Qu) could remarkably increase the retention of D-luciferin in MCF-7/DOX(Fluc)in vitro and in vivo. Also, the combination of Qu and DOX could exceedingly inhibit the tumor growth, which proved the feasibility of this in vitro screening method. The study proposed a feasible method for mass screening of MDR agents from TCMs in vitro.
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spelling pubmed-99098232023-02-10 Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells Zhao, Yue Tang, Chaoyuan Huang, Jingyi Zhang, Hongyan Shi, Jingbin Xu, Shujun Ma, Lisha Peng, Chun Liu, Qi Xiong, Yang ACS Omega [Image: see text] In this study, we established a simple and rapid in vitro method for screening multidrug resistance (MDR) reversal agents in traditional Chinese medicines (TCMs), which could better correspond to the MDR reversing effect in vivo. Here, D-luciferin, a substrate for the enzyme firefly luciferase and also a substrate for ATP-binding cassette transporters (ABC transporters), was used as the probe to detect its efflux kinetics caused by ABC transporters. First, we established a stable doxorubicin (DOX)-resistant cell line (MCF-7/DOX(Fluc)) that overexpressed luciferase. Then, some kinds of TCMs were chosen for the MDR reversal agents to measure its effect on inhibiting the D-luciferin outflow from MCF-7/DOX(Fluc), and the ideal reversal agent with the least D-luciferin efflux from MCF-7/DOX(Fluc) was selected to further investigate its effect combined with DOX on MCF-7/DOX(Fluc) tumor-bearing mice. The results indicated that quercetin (Qu) could remarkably increase the retention of D-luciferin in MCF-7/DOX(Fluc)in vitro and in vivo. Also, the combination of Qu and DOX could exceedingly inhibit the tumor growth, which proved the feasibility of this in vitro screening method. The study proposed a feasible method for mass screening of MDR agents from TCMs in vitro. American Chemical Society 2023-01-23 /pmc/articles/PMC9909823/ /pubmed/36777569 http://dx.doi.org/10.1021/acsomega.2c07096 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Zhao, Yue
Tang, Chaoyuan
Huang, Jingyi
Zhang, Hongyan
Shi, Jingbin
Xu, Shujun
Ma, Lisha
Peng, Chun
Liu, Qi
Xiong, Yang
Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells
title Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells
title_full Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells
title_fullStr Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells
title_full_unstemmed Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells
title_short Screening Multidrug Resistance Reversal Agents in Traditional Chinese Medicines by Efflux Kinetics of D-Luciferin in MCF-7/DOX(Fluc) Cells
title_sort screening multidrug resistance reversal agents in traditional chinese medicines by efflux kinetics of d-luciferin in mcf-7/dox(fluc) cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909823/
https://www.ncbi.nlm.nih.gov/pubmed/36777569
http://dx.doi.org/10.1021/acsomega.2c07096
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