Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/105792
DC Field | Value | Language |
---|---|---|
dc.contributor | Department of Applied Biology and Chemical Technology | - |
dc.contributor | Department of Health Technology and Informatics | - |
dc.creator | Sun, W | - |
dc.creator | Wong, ILK | - |
dc.creator | Law, HKW | - |
dc.creator | Su, X | - |
dc.creator | Chan, TCF | - |
dc.creator | Sun, G | - |
dc.creator | Yang, X | - |
dc.creator | Wang, X | - |
dc.creator | Chan, TH | - |
dc.creator | Wan, S | - |
dc.creator | Chow, LMC | - |
dc.date.accessioned | 2024-04-23T04:31:19Z | - |
dc.date.available | 2024-04-23T04:31:19Z | - |
dc.identifier.issn | 1661-6596 | - |
dc.identifier.uri | http://hdl.handle.net/10397/105792 | - |
dc.language.iso | en | en_US |
dc.publisher | MDPI AG | en_US |
dc.rights | Copyright: © 2023 by the authors. 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/). | en_US |
dc.rights | The following publication Sun W, Wong ILK, Law HK-W, Su X, Chan TCF, Sun G, Yang X, Wang X, Chan TH, Wan S, et al. In Vivo Reversal of P-Glycoprotein-Mediated Drug Resistance in a Breast Cancer Xenograft and in Leukemia Models Using a Novel, Potent, and Nontoxic Epicatechin EC31. International Journal of Molecular Sciences. 2023; 24(5):4377 is available at https://doi.org/10.3390/ijms24054377. | en_US |
dc.subject | EC | en_US |
dc.subject | Epicatechin | en_US |
dc.subject | MDR | en_US |
dc.subject | Modulator | en_US |
dc.subject | Multidrug resistance | en_US |
dc.subject | P-glycoprotein | en_US |
dc.subject | P-gp | en_US |
dc.title | In vivo reversal of P-glycoprotein-mediated drug resistance in a breast cancer xenograft and in leukemia models using a novel, potent, and nontoxic epicatechin EC31 | en_US |
dc.type | Journal/Magazine Article | en_US |
dc.identifier.volume | 24 | - |
dc.identifier.issue | 5 | - |
dc.identifier.doi | 10.3390/ijms24054377 | - |
dcterms.abstract | The modulation of P-glycoprotein (P-gp, ABCB1) can reverse multidrug resistance (MDR) and potentiate the efficacy of anticancer drugs. Tea polyphenols, such as epigallocatechin gallate (EGCG), have low P-gp-modulating activity, with an EC50 over 10 μM. In this study, we optimized a series of tea polyphenol derivatives and demonstrated that epicatechin EC31 was a potent and nontoxic P-gp inhibitor. Its EC50 for reversing paclitaxel, doxorubicin, and vincristine resistance in three P-gp-overexpressing cell lines ranged from 37 to 249 nM. Mechanistic studies revealed that EC31 restored intracellular drug accumulation by inhibiting P-gp-mediated drug efflux. It did not downregulate the plasma membrane P-gp level nor inhibit P-gp ATPase. It was not a transport substrate of P-gp. A pharmacokinetic study revealed that the intraperitoneal administration of 30 mg/kg of EC31 could achieve a plasma concentration above its in vitro EC50 (94 nM) for more than 18 h. It did not affect the pharmacokinetic profile of coadministered paclitaxel. In the xenograft model of the P-gp-overexpressing LCC6MDR cell line, EC31 reversed P-gp-mediated paclitaxel resistance and inhibited tumor growth by 27.4 to 36.1% (p < 0.001). Moreover, it also increased the intratumor paclitaxel level in the LCC6MDR xenograft by 6 fold (p < 0.001). In both murine leukemia P388ADR and human leukemia K562/P-gp mice models, the cotreatment of EC31 and doxorubicin significantly prolonged the survival of the mice (p < 0.001 and p < 0.01) as compared to the doxorubicin alone group, respectively. Our results suggested that EC31 was a promising candidate for further investigation on combination therapy for treating P-gp-overexpressing cancers. | - |
dcterms.accessRights | open access | en_US |
dcterms.bibliographicCitation | International journal of molecular sciences, Mar. 2023, v. 24, no. 5, 4377 | - |
dcterms.isPartOf | International journal of molecular sciences | - |
dcterms.issued | 2023-03 | - |
dc.identifier.scopus | 2-s2.0-85149834666 | - |
dc.identifier.pmid | 36901808 | - |
dc.identifier.eissn | 1422-0067 | - |
dc.identifier.artn | 4377 | - |
dc.description.validate | 202404 bcch | - |
dc.description.oa | Version of Record | en_US |
dc.identifier.FolderNumber | OA_Scopus/WOS | en_US |
dc.description.fundingSource | RGC | en_US |
dc.description.fundingSource | Others | en_US |
dc.description.fundingText | NSFC/RGC Joint Research Scheme; Project of Strategic Importance of the Hong Kong Polytechnic University; State Key Laboratory of Chemical Biology and Drug Discovery | en_US |
dc.description.pubStatus | Published | en_US |
dc.description.oaCategory | CC | en_US |
Appears in Collections: | Journal/Magazine Article |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
ijms-24-04377-v3.pdf | 10.48 MB | Adobe PDF | View/Open |
Page views
14
Citations as of Jun 30, 2024
Downloads
3
Citations as of Jun 30, 2024
SCOPUSTM
Citations
5
Citations as of Jul 4, 2024
WEB OF SCIENCETM
Citations
4
Citations as of Jul 4, 2024
![](/image/google_scholar.jpg)
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.