Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Qiaoli Zhao
- Nadine Kretschmer
- Rudolf Bauer
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000357808900024&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1002/ijc.29483
- eISSN
- 1097-0215
- Externe Identifier
- Clarivate Analytics Document Solution ID: CM6OT
- PubMed Identifier: 25688715
- ISSN
- 0020-7136
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- INTERNATIONAL JOURNAL OF CANCER
- Schlüsselwörter
- shikonin
- naphthoquinone
- epidermal growth factor receptor
- drug resistance
- synergism
- tyrosine kinase inhibitor
- Paginierung
- 1446 - 1456
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib
- Sub types
- Article
- Ausgabe der Zeitschrift
- 137
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Qiaoli Zhao
- Nadine Kretschmer
- Rudolf Bauer
- Thomas Efferth
- DOI
- 10.1002/ijc.29483
- ISSN
- 0020-7136
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- International Journal of Cancer
- Sprache
- en
- Online publication date
- 2015
- Paginierung
- 1446 - 1456
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Herausgeber
- Wiley
- Herausgeber URL
- http://dx.doi.org/10.1002/ijc.29483
- Datum der Datenerfassung
- 2021
- Titel
- Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib
- Ausgabe der Zeitschrift
- 137
Data source: Crossref
- Abstract
- Overexpression and mutation of the epidermal growth factor receptor (EGFR) gene play a causal role in tumorigenesis and resistance to treatment of glioblastoma (GBM). EGFR inhibitors such as erlotinib are currently used for the treatment of GBM; however, their efficacy has been limited due to drug resistance. New treatment strategies are therefore urgently needed. Shikonin, a natural naphthoquinone, induces both apoptosis and necroptosis in human glioma cells, but the effectiveness of erlotinib-shikonin combination treatment as well as the underlying molecular mechanisms is unknown yet. In this study, we investigated erlotinib in combination with shikonin and 14 shikonin derivatives in parental U87MG and transfected U87MG.ΔEGFR GBM cells. Most of the shikonin derivatives revealed strong cytotoxicity. Shikonin together with five other derivatives, namely deoxyshikonin, isobutyrylshikonin, acetylshikonin, β,β-dimethylacrylshikonin and acetylalkannin showed synergistic cytotoxicity toward U87MG.ΔEGFR in combination with erlotinib. Moreover, the combined cytotoxic effect of shikonin and erlotinib was further confirmed with another three EGFR-expressing cell lines, BS153, A431 and DK-MG. Shikonin not only dose-dependently inhibited EGFR phosphorylation and decreased phosphorylation of EGFR downstream molecules, including AKT, P44/42MAPK and PLCγ1, but also together with erlotinib synergistically inhibited ΔEGFR phosphorylation in U87MG.ΔEGFR cells as determined by Loewe additivity and Bliss independence drug interaction models. These results suggest that the combination of erlotinib with shikonin or its derivatives might be a potential strategy to overcome drug resistance to erlotinib.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany.
- Autoren
- Qiaoli Zhao
- Nadine Kretschmer
- Rudolf Bauer
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1002/ijc.29483
- eISSN
- 1097-0215
- Externe Identifier
- PubMed Identifier: 25688715
- Open access
- false
- ISSN
- 0020-7136
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- International journal of cancer
- Schlüsselwörter
- Cell Line, Tumor
- Humans
- Glioblastoma
- Anthraquinones
- Naphthoquinones
- Quinazolines
- Mitogen-Activated Protein Kinases
- Antineoplastic Combined Chemotherapy Protocols
- Signal Transduction
- Phosphorylation
- Drug Synergism
- Proto-Oncogene Proteins c-akt
- ErbB Receptors
- Erlotinib Hydrochloride
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2015
- Paginierung
- 1446 - 1456
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 137
Data source: Europe PubMed Central
- Abstract
- Overexpression and mutation of the epidermal growth factor receptor (EGFR) gene play a causal role in tumorigenesis and resistance to treatment of glioblastoma (GBM). EGFR inhibitors such as erlotinib are currently used for the treatment of GBM; however, their efficacy has been limited due to drug resistance. New treatment strategies are therefore urgently needed. Shikonin, a natural naphthoquinone, induces both apoptosis and necroptosis in human glioma cells, but the effectiveness of erlotinib-shikonin combination treatment as well as the underlying molecular mechanisms is unknown yet. In this study, we investigated erlotinib in combination with shikonin and 14 shikonin derivatives in parental U87MG and transfected U87MG.ΔEGFR GBM cells. Most of the shikonin derivatives revealed strong cytotoxicity. Shikonin together with five other derivatives, namely deoxyshikonin, isobutyrylshikonin, acetylshikonin, β,β-dimethylacrylshikonin and acetylalkannin showed synergistic cytotoxicity toward U87MG.ΔEGFR in combination with erlotinib. Moreover, the combined cytotoxic effect of shikonin and erlotinib was further confirmed with another three EGFR-expressing cell lines, BS153, A431 and DK-MG. Shikonin not only dose-dependently inhibited EGFR phosphorylation and decreased phosphorylation of EGFR downstream molecules, including AKT, P44/42MAPK and PLCγ1, but also together with erlotinib synergistically inhibited ΔEGFR phosphorylation in U87MG.ΔEGFR cells as determined by Loewe additivity and Bliss independence drug interaction models. These results suggest that the combination of erlotinib with shikonin or its derivatives might be a potential strategy to overcome drug resistance to erlotinib.
- Date of acceptance
- 2015
- Autoren
- Qiaoli Zhao
- Nadine Kretschmer
- Rudolf Bauer
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/25688715
- DOI
- 10.1002/ijc.29483
- eISSN
- 1097-0215
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Int J Cancer
- Schlüsselwörter
- drug resistance
- epidermal growth factor receptor
- naphthoquinone
- shikonin
- synergism
- tyrosine kinase inhibitor
- Anthraquinones
- Antineoplastic Combined Chemotherapy Protocols
- Cell Line, Tumor
- Drug Synergism
- ErbB Receptors
- Erlotinib Hydrochloride
- Glioblastoma
- Humans
- Mitogen-Activated Protein Kinases
- Naphthoquinones
- Phosphorylation
- Proto-Oncogene Proteins c-akt
- Quinazolines
- Signal Transduction
- Sprache
- eng
- Country
- United States
- Paginierung
- 1446 - 1456
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2015
- Titel
- Shikonin and its derivatives inhibit the epidermal growth factor receptor signaling and synergistically kill glioblastoma cells in combination with erlotinib.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 137
Data source: PubMed
- Beziehungen:
- Property of