Inhibition of epidermal growth factor receptor over-expressing cancer cells by the aphorphine-type isoquinoline alkaloid, dicentrine

Publication type:
Journal article
Metadata:
Autoren
  • V Badireenath Konkimalla
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000275391400002&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.bcp.2009.11.025
eISSN
1873-2968
Externe Identifier
  • Clarivate Analytics Document Solution ID: 566RT
  • PubMed Identifier: 20005213
ISSN
0006-2952
Ausgabe der Veröffentlichung
8
Zeitschrift
BIOCHEMICAL PHARMACOLOGY
Schlüsselwörter
  • Microarrays
  • Natural product
  • Oncogenes
  • Pharmacology
  • Pharmacogenomics
  • Pharmacognosy
  • Signal transduction
  • Systems biology
Paginierung
1092 - 1099
Datum der Veröffentlichung
2010
Status
Published
Titel
Inhibition of epidermal growth factor receptor over-expressing cancer cells by the aphorphine-type isoquinoline alkaloid, dicentrine
Sub types
  • Article
Ausgabe der Zeitschrift
79

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • V Badireenath Konkimalla
  • Thomas Efferth
DOI
10.1016/j.bcp.2009.11.025
ISSN
0006-2952
Ausgabe der Veröffentlichung
8
Zeitschrift
Biochemical Pharmacology
Sprache
en
Paginierung
1092 - 1099
Datum der Veröffentlichung
2010
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.bcp.2009.11.025
Datum der Datenerfassung
2018
Titel
Inhibition of epidermal growth factor receptor over-expressing cancer cells by the aphorphine-type isoquinoline alkaloid, dicentrine
Ausgabe der Zeitschrift
79

Data source: Crossref

Abstract
The extraordinary relevance of EGFR in tumour biology makes it an exquisite molecular target for tumour therapy. Despite considerable success with these EGFR tyrosine kinase inhibitors in cancer therapy, resistance against these chemical compounds develops owing to the selection of point-mutated variants of EGFR. Therefore, there is an urgent need for the identification of novel EGFR tyrosine kinase inhibitors for treating tumours with such EGFR mutants. We found a preferential cytotoxicity of dicentrine towards U87MG.DeltaEGFR-transduced with a constitutively deletion-activated EGFR expression vector as compared to non-transduced wild-type U87MG cells. As determined by microarray-based mRNA expression profiling, this preferential cytotoxicity was accompanied with an activation of BRCA1-mediated DNA damage response, p53 signalling, G1/S and G2/M cell cycle regulation, and aryl hydrocarbon receptor pathways. The activation of these signalling routes might be explained by the fact that dicentrine intercalates DNA and induces DNA strand break by inhibition of DNA topoisomerases. The cell cycle might be arrested by dicentrine-induced DNA lesions.
Addresses
  • German Cancer Research Center, Heidelberg, Germany.
Autoren
DOI
10.1016/j.bcp.2009.11.025
eISSN
1873-2968
Externe Identifier
  • PubMed Identifier: 20005213
Funding acknowledgements
  • Dietmar Hopp-Foundation:
Open access
false
ISSN
0006-2952
Ausgabe der Veröffentlichung
8
Zeitschrift
Biochemical pharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • DNA Damage
  • Aporphines
  • BRCA1 Protein
  • Antineoplastic Agents
  • Gene Expression Profiling
  • Reverse Transcriptase Polymerase Chain Reaction
  • Cell Cycle
  • Apoptosis
  • Dose-Response Relationship, Drug
  • ErbB Receptors
Sprache
eng
Medium
Print-Electronic
Online publication date
2009
Paginierung
1092 - 1099
Datum der Veröffentlichung
2010
Status
Published
Datum der Datenerfassung
2009
Titel
Inhibition of epidermal growth factor receptor over-expressing cancer cells by the aphorphine-type isoquinoline alkaloid, dicentrine.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
79

Data source: Europe PubMed Central

Abstract
The extraordinary relevance of EGFR in tumour biology makes it an exquisite molecular target for tumour therapy. Despite considerable success with these EGFR tyrosine kinase inhibitors in cancer therapy, resistance against these chemical compounds develops owing to the selection of point-mutated variants of EGFR. Therefore, there is an urgent need for the identification of novel EGFR tyrosine kinase inhibitors for treating tumours with such EGFR mutants. We found a preferential cytotoxicity of dicentrine towards U87MG.DeltaEGFR-transduced with a constitutively deletion-activated EGFR expression vector as compared to non-transduced wild-type U87MG cells. As determined by microarray-based mRNA expression profiling, this preferential cytotoxicity was accompanied with an activation of BRCA1-mediated DNA damage response, p53 signalling, G1/S and G2/M cell cycle regulation, and aryl hydrocarbon receptor pathways. The activation of these signalling routes might be explained by the fact that dicentrine intercalates DNA and induces DNA strand break by inhibition of DNA topoisomerases. The cell cycle might be arrested by dicentrine-induced DNA lesions.
Date of acceptance
2009
Autoren
  • V Badireenath Konkimalla
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/20005213
DOI
10.1016/j.bcp.2009.11.025
eISSN
1873-2968
Ausgabe der Veröffentlichung
8
Zeitschrift
Biochem Pharmacol
Schlüsselwörter
  • Antineoplastic Agents
  • Apoptosis
  • Aporphines
  • BRCA1 Protein
  • Cell Cycle
  • Cell Line, Tumor
  • DNA Damage
  • Dose-Response Relationship, Drug
  • ErbB Receptors
  • Gene Expression Profiling
  • Humans
  • Reverse Transcriptase Polymerase Chain Reaction
Sprache
eng
Country
England
Paginierung
1092 - 1099
PII
S0006-2952(09)01064-8
Datum der Veröffentlichung
2010
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2010
Titel
Inhibition of epidermal growth factor receptor over-expressing cancer cells by the aphorphine-type isoquinoline alkaloid, dicentrine.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
79

Data source: PubMed

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