Collateral sensitivity of drug-resistant ABCB5-and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expression

Publication type:
Journal article
Metadata:
Autoren
  • Mohamed EM Saeed
  • Muhammad Rahama
  • Victor Kuete
  • Mona Dawooda
  • Mohamed Elbadawi
  • Yoshikazu Sugimoto
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000473048600022&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2019.152890
eISSN
1618-095X
Externe Identifier
  • Clarivate Analytics Document Solution ID: IF4JW
  • PubMed Identifier: 30921566
ISSN
0944-7113
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Cancer
  • Drug resistance
  • Sirtuins
  • Microarray
  • Pharmacogenomics
  • Phytoalexin
Artikelnummer
ARTN 152890
Datum der Veröffentlichung
2019
Status
Published
Titel
Collateral sensitivity of drug-resistant ABCB5-and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expression
Sub types
  • Article
Ausgabe der Zeitschrift
59

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Mohamed EM Saeed
  • Muhammad Rahama
  • Victor Kuete
  • Mona Dawood
  • Mohamed Elbadawi
  • Yoshikazu Sugimoto
  • Thomas Efferth
DOI
10.1016/j.phymed.2019.152890
ISSN
0944-7113
Zeitschrift
Phytomedicine
Sprache
en
Artikelnummer
152890
Paginierung
152890 - 152890
Datum der Veröffentlichung
2019
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2019.152890
Datum der Datenerfassung
2019
Titel
Collateral sensitivity of drug-resistant ABCB5- and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expression
Ausgabe der Zeitschrift
59

Data source: Crossref

Abstract
<h4>Background</h4>In the drug discovery field, natural products deemed a precious source of novel lead compounds. They have the ability to bypass or overcome multidrug resistance (MDR) in cancer cells.<h4>Purpose</h4>In this study, the natural polyphenolic stilbene resveratrol (RES) has been studied for its cytotoxic activity toward MDR cancer cells.<h4>Methods</h4>Resazurin assay was used to investigate the cytotoxicity of RES not only against a panel of drug-resistant cancer cells overexpressing P-glycoprotein/ABCB1, BCRP/ABCG2, ABCB5 (ATP-binding cassette transporters), but also mutation-activated EGFR. The assessment of proteins expression was done by Western blot analysis. COMPARE and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to RES. The NF-κB activation was evaluated using NF-kB reporter cells assay.<h4>Results</h4>Interestingly, MDR cells overexpressing ABCB5 and mutation-activated EGFR were collateral sensitive (CS) to RES. Our immunoblotting analysis highlighted that CS may be attributed to RES-induced sirtuin 1 (SIRT1) overexpression. Indeed, the SIRT1 inhibitor, sirtinol completely abolished CS to RES, indicating a causative role of SIRT1 for CS to RES. In addition, COMPARE and hierarchical cluster analyses of transcriptomic data indicated genes associated with diverse cellular mechanisms ranging from the immune response, inflammation signaling, and microtubule formation to cell migration. Searching for transcription factor binding motifs in the promoters of these genes pointed to NF-κB as one of the master regulators related to RES activity.<h4>Conclusion</h4>The findings demonstrate that RES alone or in combination with established chemotherapeutic agents might overcome the refractory tumors. This information may be immensely useful for the development of personalized treatment.
Addresses
  • Department of Pharmaceutical Biology, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
Autoren
  • Mohamed EM Saeed
  • Muhammad Rahama
  • Victor Kuete
  • Mona Dawood
  • Mohamed Elbadawi
  • Yoshikazu Sugimoto
  • Thomas Efferth
DOI
10.1016/j.phymed.2019.152890
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 30921566
Open access
false
ISSN
0944-7113
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • NF-kappa B
  • Antineoplastic Agents, Phytogenic
  • Drug Resistance, Multiple
  • Gene Expression Regulation, Neoplastic
  • Drug Resistance, Neoplasm
  • Mutation
  • Promoter Regions, Genetic
  • Sirtuin 1
  • ErbB Receptors
  • Resveratrol
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
Sprache
eng
Medium
Print-Electronic
Online publication date
2019
Paginierung
152890
Datum der Veröffentlichung
2019
Status
Published
Datum der Datenerfassung
2019
Titel
Collateral sensitivity of drug-resistant ABCB5- and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expression.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
59

Data source: Europe PubMed Central

Abstract
BACKGROUND: In the drug discovery field, natural products deemed a precious source of novel lead compounds. They have the ability to bypass or overcome multidrug resistance (MDR) in cancer cells. PURPOSE: In this study, the natural polyphenolic stilbene resveratrol (RES) has been studied for its cytotoxic activity toward MDR cancer cells. METHODS: Resazurin assay was used to investigate the cytotoxicity of RES not only against a panel of drug-resistant cancer cells overexpressing P-glycoprotein/ABCB1, BCRP/ABCG2, ABCB5 (ATP-binding cassette transporters), but also mutation-activated EGFR. The assessment of proteins expression was done by Western blot analysis. COMPARE and hierarchical cluster analyses were applied to identify, which genes correlate with sensitivity or resistance to RES. The NF-κB activation was evaluated using NF-kB reporter cells assay. RESULTS: Interestingly, MDR cells overexpressing ABCB5 and mutation-activated EGFR were collateral sensitive (CS) to RES. Our immunoblotting analysis highlighted that CS may be attributed to RES-induced sirtuin 1 (SIRT1) overexpression. Indeed, the SIRT1 inhibitor, sirtinol completely abolished CS to RES, indicating a causative role of SIRT1 for CS to RES. In addition, COMPARE and hierarchical cluster analyses of transcriptomic data indicated genes associated with diverse cellular mechanisms ranging from the immune response, inflammation signaling, and microtubule formation to cell migration. Searching for transcription factor binding motifs in the promoters of these genes pointed to NF-κB as one of the master regulators related to RES activity. CONCLUSION: The findings demonstrate that RES alone or in combination with established chemotherapeutic agents might overcome the refractory tumors. This information may be immensely useful for the development of personalized treatment.
Date of acceptance
2019
Autoren
  • Mohamed EM Saeed
  • Muhammad Rahama
  • Victor Kuete
  • Mona Dawood
  • Mohamed Elbadawi
  • Yoshikazu Sugimoto
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30921566
DOI
10.1016/j.phymed.2019.152890
eISSN
1618-095X
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Cancer
  • Drug resistance
  • Microarray
  • Pharmacogenomics
  • Phytoalexin
  • Sirtuins
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Cell Line, Tumor
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • ErbB Receptors
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutation
  • NF-kappa B
  • Promoter Regions, Genetic
  • Resveratrol
  • Sirtuin 1
Sprache
eng
Country
Germany
Paginierung
152890
PII
S0944-7113(19)30060-1
Datum der Veröffentlichung
2019
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2019
Titel
Collateral sensitivity of drug-resistant ABCB5- and mutation-activated EGFR overexpressing cells towards resveratrol due to modulation of SIRT1 expression.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
59

Data source: PubMed

Beziehungen:
Property of

Tools