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Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase
Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying me...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963356/ https://www.ncbi.nlm.nih.gov/pubmed/37259354 http://dx.doi.org/10.3390/ph16020205 |
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author | Wu, I-Ting Kuo, Chan-Yen Su, Ching-Hui Lan, Yu-Hsuan Hung, Chin-Chuan |
author_facet | Wu, I-Ting Kuo, Chan-Yen Su, Ching-Hui Lan, Yu-Hsuan Hung, Chin-Chuan |
author_sort | Wu, I-Ting |
collection | PubMed |
description | Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate efflux assays, multidrug resistance 1 (MDR1) shift assays, P-gp ATPase activity assays, Western blotting, and docking simulation were performed. The potential of the test compounds for MDR reversal and the associated molecular mechanisms were investigated through cell viability assay, cell cycle analysis, apoptosis assay, and further determining the combination index. Results demonstrated that pinostrobin and tectochrysin were not the substrates of P-gp, nor did they affect the expression of this transporter. Both compounds noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp. Furthermore, they resensitized MDR cancer cells to chemotherapeutic drugs, such as vincristine, paclitaxel, and docetaxel; thus, they exhibited strong MDR reversal effects. Our findings indicate that pinostrobin and tectochrysin are effective P-gp inhibitors and promising candidates for resensitizing MDR cancer cells. |
format | Online Article Text |
id | pubmed-9963356 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99633562023-02-26 Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase Wu, I-Ting Kuo, Chan-Yen Su, Ching-Hui Lan, Yu-Hsuan Hung, Chin-Chuan Pharmaceuticals (Basel) Article Enhanced drug efflux through ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), is a key mechanism underlying multidrug resistance (MDR). In the present study, we investigated the inhibitory effects of pinostrobin and tectochrysin on P-gp in MDR cancer cells and the underlying mechanisms. Fluorescence substrate efflux assays, multidrug resistance 1 (MDR1) shift assays, P-gp ATPase activity assays, Western blotting, and docking simulation were performed. The potential of the test compounds for MDR reversal and the associated molecular mechanisms were investigated through cell viability assay, cell cycle analysis, apoptosis assay, and further determining the combination index. Results demonstrated that pinostrobin and tectochrysin were not the substrates of P-gp, nor did they affect the expression of this transporter. Both compounds noncompetitively inhibited the efflux of rhodamine 123 and doxorubicin through P-gp. Furthermore, they resensitized MDR cancer cells to chemotherapeutic drugs, such as vincristine, paclitaxel, and docetaxel; thus, they exhibited strong MDR reversal effects. Our findings indicate that pinostrobin and tectochrysin are effective P-gp inhibitors and promising candidates for resensitizing MDR cancer cells. MDPI 2023-01-29 /pmc/articles/PMC9963356/ /pubmed/37259354 http://dx.doi.org/10.3390/ph16020205 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wu, I-Ting Kuo, Chan-Yen Su, Ching-Hui Lan, Yu-Hsuan Hung, Chin-Chuan Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase |
title | Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase |
title_full | Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase |
title_fullStr | Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase |
title_full_unstemmed | Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase |
title_short | Pinostrobin and Tectochrysin Conquer Multidrug-Resistant Cancer Cells via Inhibiting P-Glycoprotein ATPase |
title_sort | pinostrobin and tectochrysin conquer multidrug-resistant cancer cells via inhibiting p-glycoprotein atpase |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9963356/ https://www.ncbi.nlm.nih.gov/pubmed/37259354 http://dx.doi.org/10.3390/ph16020205 |
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