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Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance
Multidrug resistance (MDR) of tumor cells to chemotherapeutic agents is the main reason for the failure of cancer chemotherapy. Overexpression of ABCB1 transporter that actively pumps various drugs out of the cells has been considered a major contributing factor for MDR. Over the past decade, many a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438908/ https://www.ncbi.nlm.nih.gov/pubmed/32903706 http://dx.doi.org/10.3389/fphar.2020.01208 |
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author | Luo, Xiaofang Teng, Qiu-Xu Dong, Jin-Yun Yang, Dong-Hua Wang, Meifeng Dessie, Wubliker Qin, Jiang-Jiang Lei, Zi-Ning Wang, Jing-Quan Qin, Zuodong Chen, Zhe-Sheng |
author_facet | Luo, Xiaofang Teng, Qiu-Xu Dong, Jin-Yun Yang, Dong-Hua Wang, Meifeng Dessie, Wubliker Qin, Jiang-Jiang Lei, Zi-Ning Wang, Jing-Quan Qin, Zuodong Chen, Zhe-Sheng |
author_sort | Luo, Xiaofang |
collection | PubMed |
description | Multidrug resistance (MDR) of tumor cells to chemotherapeutic agents is the main reason for the failure of cancer chemotherapy. Overexpression of ABCB1 transporter that actively pumps various drugs out of the cells has been considered a major contributing factor for MDR. Over the past decade, many antimicrobial peptides with antitumor activity have been identified or synthesized, and some antitumor peptides have entered the clinical practice. In this study, we report that peptide HX-12C has the effect of reversing ABCB1-mediated chemotherapy resistance. In ABCB1-overexpressing cells, nontoxic dose of peptide HX-12C inhibited drug resistance and increased the effective intracellular concentration of paclitaxel and other ABCB1 substrate drugs. The mechanism study showed that peptide HX-12C stimulated ABCB1 ATPase activity without changing the expression level and localization patterns of ABCB1. Molecular docking predicted the binding modes between peptide HX-12C and ABCB1. Overall, we found that peptide HX-12C reverses ABCB1-mediated MDR through interacting with ABCB1 and blocking its function without affecting the transporter’s expression and cellular localization. Our findings suggest that this antimicrobial peptide may be used as a novel prospective cancer therapeutic strategy in combination with conventional anticancer agents. |
format | Online Article Text |
id | pubmed-7438908 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74389082020-09-03 Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance Luo, Xiaofang Teng, Qiu-Xu Dong, Jin-Yun Yang, Dong-Hua Wang, Meifeng Dessie, Wubliker Qin, Jiang-Jiang Lei, Zi-Ning Wang, Jing-Quan Qin, Zuodong Chen, Zhe-Sheng Front Pharmacol Pharmacology Multidrug resistance (MDR) of tumor cells to chemotherapeutic agents is the main reason for the failure of cancer chemotherapy. Overexpression of ABCB1 transporter that actively pumps various drugs out of the cells has been considered a major contributing factor for MDR. Over the past decade, many antimicrobial peptides with antitumor activity have been identified or synthesized, and some antitumor peptides have entered the clinical practice. In this study, we report that peptide HX-12C has the effect of reversing ABCB1-mediated chemotherapy resistance. In ABCB1-overexpressing cells, nontoxic dose of peptide HX-12C inhibited drug resistance and increased the effective intracellular concentration of paclitaxel and other ABCB1 substrate drugs. The mechanism study showed that peptide HX-12C stimulated ABCB1 ATPase activity without changing the expression level and localization patterns of ABCB1. Molecular docking predicted the binding modes between peptide HX-12C and ABCB1. Overall, we found that peptide HX-12C reverses ABCB1-mediated MDR through interacting with ABCB1 and blocking its function without affecting the transporter’s expression and cellular localization. Our findings suggest that this antimicrobial peptide may be used as a novel prospective cancer therapeutic strategy in combination with conventional anticancer agents. Frontiers Media S.A. 2020-08-07 /pmc/articles/PMC7438908/ /pubmed/32903706 http://dx.doi.org/10.3389/fphar.2020.01208 Text en Copyright © 2020 Luo, Teng, Dong, Yang, Wang, Dessie, Qin, Lei, Wang, Qin and Chen http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Luo, Xiaofang Teng, Qiu-Xu Dong, Jin-Yun Yang, Dong-Hua Wang, Meifeng Dessie, Wubliker Qin, Jiang-Jiang Lei, Zi-Ning Wang, Jing-Quan Qin, Zuodong Chen, Zhe-Sheng Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance |
title | Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance |
title_full | Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance |
title_fullStr | Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance |
title_full_unstemmed | Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance |
title_short | Antimicrobial Peptide Reverses ABCB1-Mediated Chemotherapeutic Drug Resistance |
title_sort | antimicrobial peptide reverses abcb1-mediated chemotherapeutic drug resistance |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438908/ https://www.ncbi.nlm.nih.gov/pubmed/32903706 http://dx.doi.org/10.3389/fphar.2020.01208 |
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