Evidence map›Paper›PMID 28893612›Full record

ArticleCancer letters2017

Tyrphostin RG14620 selectively reverses ABCG2-mediated multidrug resistance in cancer cell lines.

Chung-Pu Wu, Sung-Han Hsiao, Megumi Murakami, Ming-Jie Lu, Yan-Qing Li, Chia-Hung Hsieh, Suresh V Ambudkar, Yu-Shan Wu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.4field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 21 citations in OpenAlex.

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  12. ILC2s: New Actors in Tumor Immunity.Frontiers in immunology · 2019
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

Chung-Pu WuGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Molecular Medicine Research Center, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan. Electronic address: wuchung@mail.cgu.edu.tw.
Sung-Han HsiaoGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Megumi MurakamiLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, United States.
Ming-Jie LuGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Yan-Qing LiGraduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan; Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Chia-Hung HsiehGraduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Biomedical Informatics, Asia University, Taichung, Taiwan.
Suresh V AmbudkarLaboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, United States.
Yu-Shan WuDepartment of Chemistry, Tunghai University, Taichung, Taiwan. Electronic address: yushanwu@thu.edu.tw.
Chang Gung University · TWNational Cancer Institute · USAsia University · TWTunghai University · TW

Funding

Biochemical Analysis of Multidrug Resistance-linked Transport ProteinsZIABC010030 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI AMBUDKAR, SURESH · 2009 to 2025
$21.6M
Intramural NIH HHS ZIA BC010030
6 · The paper itself

Abstract

The multidrug resistance (MDR) phenotype associated with the overexpression of ATP-binding cassette (ABC) drug transporters ABCB1, ABCC1 and ABCG2 is a major obstacle in cancer chemotherapy. Numerous epidermal growth factor receptor (EGFR) inhibitors have previously been shown capable of reversing MDR in ABCG2-overexpressing cancer cells. However, most of them are not transporter-specific due to the substantial overlapping substrate specificity among the transporters. In this study, we investigated the interaction between ABCG2 and tyrphostin RG14620, an EGFR inhibitor of the tyrphostin family, in multidrug-resistant cancer cell lines. We found that at nontoxic concentrations, tyrphostin RG14620 enhances drug-induced apoptosis and restores chemosensitivity to ABCG2-overexpressing multidrug-resistant cancer cells. More importantly, tyrphostin RG14620 is selective to ABCG2 relative to ABCB1 and ABCC1. Our findings were further supported by biochemical assays demonstrating that tyrphostin RG14620 stimulates ATP hydrolysis and inhibits photoaffinity labeling of ABCG2 with IAAP, and by a docking analysis of tyrphostin RG14620 in the drug-binding pocket of this transporter. Taken together, our findings indicate that tyrphostin RG14620 is a potent and selective modulator of ABCG2 that may be useful to overcome chemoresistance in patients with drug-resistant tumors.

Indexed as

ATP Binding Cassette Transporter, Subfamily G, Member 2Cell Line, TumorDrug Resistance, MultipleDrug Resistance, NeoplasmDrug Screening Assays, AntitumorErbB ReceptorsHEK293 CellsHumansNeoplasm ProteinsNeoplasmsProtein Kinase InhibitorsTyrphostinsABCG2 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 2EGFR protein, humanErbB ReceptorsNeoplasm ProteinsProtein Kinase InhibitorsRG 14620TyrphostinsABCG2ABC transporterEGFR inhibitorMultidrug resistanceTyrphostin RG14620

Identifiers

PMID28893612
PMCPMC5634936
OpenAlexW2753365194

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.