Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine

Publication type:
Journal article
Metadata:
Autoren
  • Mohamed EM Saeed
  • Nuha Mahmoud
  • Yoshikazu Sugimoto
  • Thomas Efferth
  • Heba Abdel-Aziz
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000426056800001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3389/fphar.2018.00136
Externe Identifier
  • Clarivate Analytics Document Solution ID: FX4OD
  • PubMed Identifier: 29535628
ISSN
1663-9812
Zeitschrift
FRONTIERS IN PHARMACOLOGY
Schlüsselwörter
  • bioinformatics
  • cancer
  • drug resistance
  • microarray
  • pharmacogenomics
  • phytotherapy
Artikelnummer
ARTN 136
Datum der Veröffentlichung
2018
Status
Published
Titel
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine
Sub types
  • Article
Ausgabe der Zeitschrift
9

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Mohamed EM Saeed
  • Nuha Mahmoud
  • Yoshikazu Sugimoto
  • Thomas Efferth
  • Heba Abdel-Aziz
DOI
10.3389/fphar.2018.00136
eISSN
1663-9812
Zeitschrift
Frontiers in Pharmacology
Online publication date
2018
Status
Published online
Herausgeber
Frontiers Media SA
Herausgeber URL
http://dx.doi.org/10.3389/fphar.2018.00136
Datum der Datenerfassung
2022
Titel
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine
Ausgabe der Zeitschrift
9

Data source: Crossref

Abstract
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR). Multidrug resistant cells overexpressing BCRP, ABCB5 and mutated ΔEGFR were not cross-resistant toward sanguinarine. Interestingly, P-gp overexpressing cells were hypersensitive to sanguinarine. Doxorubicin uptake assay carried by flow cytometry revealed that sanguinarine is a potent inhibitor of the P-gp transporter. Moreover, immunoblotting analysis proved that P-gp was downregulated in a dose dependent manner after treating P-gp overexpressing cells with sanguinarine. It was surmised that The inhibition of NFκB activity might explain the collateral sensitivity in CEM/ADR5000 cells. The COMPARE and hierarchical cluster analyses of transcriptome-wide expression profiles of tumor cell lines of the National Cancer Institute identified genes involved in various cellular processes (immune response, inflammation signaling, cell migration and microtubule formation) significantly correlated with log<sub>10</sub>IC<sub>50</sub> values for sanguinarine. In conclusion, sanguinarine may have therapeutic potential for treating multidrug resistant tumors.
Addresses
  • Department of Pharmaceutical Biology, Johannes Gutenberg University, Mainz, Germany.
Autoren
  • Mohamed EM Saeed
  • Nuha Mahmoud
  • Yoshikazu Sugimoto
  • Thomas Efferth
  • Thomas Efferth
  • Heba Abdel-Aziz
DOI
10.3389/fphar.2018.00136
eISSN
1663-9812
Externe Identifier
  • PubMed Identifier: 29535628
  • PubMed Central ID: PMC5834429
Open access
true
ISSN
1663-9812
Zeitschrift
Frontiers in pharmacology
Sprache
eng
Medium
Electronic-eCollection
Online publication date
2018
Open access status
Open Access
Paginierung
136
Datum der Veröffentlichung
2018
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2018
Titel
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
9

Files

https://www.frontiersin.org/articles/10.3389/fphar.2018.00136/pdf https://europepmc.org/articles/PMC5834429?pdf=render

Data source: Europe PubMed Central

Abstract
For decades, natural products represented a significant source of diverse and unique bioactive lead compounds in drug discovery field. In Clinical oncology, complete tumors remission is hampered by the development of drug-resistance. Therefore, development of cytotoxic agents that may overcome drug resistance is urgently needed. Here, the natural benzophenanthridine alkaloid sanguinarine has been studied for its cytotoxic activity against multidrug resistance (MDR) cancer cells. We investigated the role of the ATP-binding cassette (ABC) transporters BCRP/ABCG2, P-glycoprotein/ABCB1 and its close relative ABCB5 in drug resistance. Further drug resistance mechanisms analyzed in this study were the tumor suppressor TP53 and the epidermal growth factor receptor (EGFR). Multidrug resistant cells overexpressing BCRP, ABCB5 and mutated ΔEGFR were not cross-resistant toward sanguinarine. Interestingly, P-gp overexpressing cells were hypersensitive to sanguinarine. Doxorubicin uptake assay carried by flow cytometry revealed that sanguinarine is a potent inhibitor of the P-gp transporter. Moreover, immunoblotting analysis proved that P-gp was downregulated in a dose dependent manner after treating P-gp overexpressing cells with sanguinarine. It was surmised that The inhibition of NFκB activity might explain the collateral sensitivity in CEM/ADR5000 cells. The COMPARE and hierarchical cluster analyses of transcriptome-wide expression profiles of tumor cell lines of the National Cancer Institute identified genes involved in various cellular processes (immune response, inflammation signaling, cell migration and microtubule formation) significantly correlated with log10IC50 values for sanguinarine. In conclusion, sanguinarine may have therapeutic potential for treating multidrug resistant tumors.
Date of acceptance
2018
Autoren
  • Mohamed EM Saeed
  • Nuha Mahmoud
  • Yoshikazu Sugimoto
  • Thomas Efferth
  • Heba Abdel-Aziz
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/29535628
DOI
10.3389/fphar.2018.00136
Externe Identifier
  • PubMed Central ID: PMC5834429
ISSN
1663-9812
Zeitschrift
Front Pharmacol
Schlüsselwörter
  • bioinformatics
  • cancer
  • drug resistance
  • microarray
  • pharmacogenomics
  • phytotherapy
Sprache
eng
Country
Switzerland
Paginierung
136
Datum der Veröffentlichung
2018
Status
Published online
Titel
Molecular Determinants of Sensitivity or Resistance of Cancer Cells Toward Sanguinarine.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
9

Data source: PubMed

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