Vitamin K3 thio-derivative: a novel specific apoptotic inducer in the doxorubicin-sensitive and -resistant cancer cells
- Publication type:
- Journal article
- Metadata:
-
- Autoren
- Mohamed-Elamir F Hegazy
- Masashi Fukaya
- Mona Dawood
- Ge Yan
- Anette Klinger
- Edmond Fleischer
- Asmaa W Zaglool
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000531213000009&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1007/s10637-019-00810-7
- eISSN
- 1573-0646
- Externe Identifier
- Clarivate Analytics Document Solution ID: LK9XS
- PubMed Identifier: 31254176
- ISSN
- 0167-6997
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- INVESTIGATIONAL NEW DRUGS
- Schlüsselwörter
- Vitamin K-3 derivatives
- Cytotoxicity
- Apoptosis
- Cell cycle
- Microtubules
- Cell migration
- Leukemia
- Paginierung
- 650 - 661
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Titel
- Vitamin K<sub>3</sub> thio-derivative: a novel specific apoptotic inducer in the doxorubicin-sensitive and -resistant cancer cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 38
Data source: Web of Science (Lite)
- Other metadata sources:
-
- Autoren
- Mohamed-Elamir F Hegazy
- Masashi Fukaya
- Mona Dawood
- Ge Yan
- Anette Klinger
- Edmond Fleischer
- Asmaa W Zaglool
- Thomas Efferth
- DOI
- 10.1007/s10637-019-00810-7
- eISSN
- 1573-0646
- ISSN
- 0167-6997
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Investigational New Drugs
- Sprache
- en
- Online publication date
- 2019
- Paginierung
- 650 - 661
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Herausgeber
- Springer Science and Business Media LLC
- Herausgeber URL
- http://dx.doi.org/10.1007/s10637-019-00810-7
- Datum der Datenerfassung
- 2023
- Titel
- Vitamin K3 thio-derivative: a novel specific apoptotic inducer in the doxorubicin-sensitive and -resistant cancer cells
- Ausgabe der Zeitschrift
- 38
Data source: Crossref
- Abstract
- Vitamin K<sub>3</sub>, also known as menadione, is a synthetic lipid-soluble 2-methyl-1,4- naphthoquinone analogs of vitamin K. The vitamin K derivatives exhibit potent cytotoxicity against several cancer cell lines through ROS induction and mitochondrial dysfunction. We investigated vitamin K<sub>3</sub>-inspired derivatives as potential apoptotic inducers and analyzed their mechanisms beyond apoptosis. The cytotoxicity of a panel of vitamin K<sub>3</sub> analogs was screened against 10 doxorubicin-sensitive and -resistant cancer cell lines overexpressing ATP-binding cassette transporters (P-glycoprotein, ABCB5, BCRP) or oncogenes (ΔEGFR) or with knockout of tumor suppressors (p53), Cell cycle arrest, apoptosis, cell migration, and microtubule formation were further investigated. The online tool SwissTargetPrediction was utilized for target prediction. Among the screened compounds, one vitamin K<sub>3</sub> thio-derivative (No. 45, VKT-1) exhibited the most potent cytotoxicity specifically against both drug-sensitive and -resistant cancer cell lines. In addition, VKT-1 arrested the cells at the G2/M phase and induced apoptosis as detected by flow cytometry. As predicted by SwissTargetPrediction, VKT-1 targeted microtubule-associated tau protein. Indeed, VKT-1 dramatically inhibited cell migration and microtubule formation in vitro. In conclusion, the synthetic vitamin K<sub>3</sub> thio-derivative (VKT-1) inhibited doxorubicin-sensitive and -resistant tumor cells by cell arrest, apoptosis induction, as well as, migration inhibition, and microtubule deterioration of U2OS-GFP-α-tubulin cells.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudingerweg 5, 55128, Mainz, Germany.
- Autoren
- Mohamed-Elamir F Hegazy
- Masashi Fukaya
- Mona Dawood
- Ge Yan
- Anette Klinger
- Edmond Fleischer
- Asmaa W Zaglool
- Thomas Efferth
- DOI
- 10.1007/s10637-019-00810-7
- eISSN
- 1573-0646
- Externe Identifier
- PubMed Identifier: 31254176
- Funding acknowledgements
- Alexander Von Humboldt:
- Open access
- false
- ISSN
- 0167-6997
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Investigational new drugs
- Schlüsselwörter
- Cell Line
- Cell Line, Tumor
- Microtubules
- Humans
- Vitamin K 3
- Doxorubicin
- Tubulin
- ATP-Binding Cassette Transporters
- Cell Division
- G2 Phase
- Apoptosis
- Cell Movement
- Drug Resistance, Neoplasm
- HEK293 Cells
- Cell Cycle Checkpoints
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2019
- Paginierung
- 650 - 661
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Datum der Datenerfassung
- 2019
- Titel
- Vitamin K<sub>3</sub> thio-derivative: a novel specific apoptotic inducer in the doxorubicin-sensitive and -resistant cancer cells.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 38
Data source: Europe PubMed Central
- Abstract
- Vitamin K3, also known as menadione, is a synthetic lipid-soluble 2-methyl-1,4- naphthoquinone analogs of vitamin K. The vitamin K derivatives exhibit potent cytotoxicity against several cancer cell lines through ROS induction and mitochondrial dysfunction. We investigated vitamin K3-inspired derivatives as potential apoptotic inducers and analyzed their mechanisms beyond apoptosis. The cytotoxicity of a panel of vitamin K3 analogs was screened against 10 doxorubicin-sensitive and -resistant cancer cell lines overexpressing ATP-binding cassette transporters (P-glycoprotein, ABCB5, BCRP) or oncogenes (ΔEGFR) or with knockout of tumor suppressors (p53), Cell cycle arrest, apoptosis, cell migration, and microtubule formation were further investigated. The online tool SwissTargetPrediction was utilized for target prediction. Among the screened compounds, one vitamin K3 thio-derivative (No. 45, VKT-1) exhibited the most potent cytotoxicity specifically against both drug-sensitive and -resistant cancer cell lines. In addition, VKT-1 arrested the cells at the G2/M phase and induced apoptosis as detected by flow cytometry. As predicted by SwissTargetPrediction, VKT-1 targeted microtubule-associated tau protein. Indeed, VKT-1 dramatically inhibited cell migration and microtubule formation in vitro. In conclusion, the synthetic vitamin K3 thio-derivative (VKT-1) inhibited doxorubicin-sensitive and -resistant tumor cells by cell arrest, apoptosis induction, as well as, migration inhibition, and microtubule deterioration of U2OS-GFP-α-tubulin cells.
- Date of acceptance
- 2019
- Autoren
- Mohamed-Elamir F Hegazy
- Masashi Fukaya
- Mona Dawood
- Ge Yan
- Anette Klinger
- Edmond Fleischer
- Asmaa W Zaglool
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/31254176
- DOI
- 10.1007/s10637-019-00810-7
- eISSN
- 1573-0646
- Ausgabe der Veröffentlichung
- 3
- Zeitschrift
- Invest New Drugs
- Schlüsselwörter
- Apoptosis
- Cell cycle
- Cell migration
- Cytotoxicity
- Leukemia
- Microtubules
- Vitamin K3 derivatives
- ATP-Binding Cassette Transporters
- Apoptosis
- Cell Cycle Checkpoints
- Cell Division
- Cell Line
- Cell Line, Tumor
- Cell Movement
- Doxorubicin
- Drug Resistance, Neoplasm
- G2 Phase
- HEK293 Cells
- Humans
- Microtubules
- Tubulin
- Vitamin K 3
- Sprache
- eng
- Country
- United States
- Paginierung
- 650 - 661
- PII
- 10.1007/s10637-019-00810-7
- Datum der Veröffentlichung
- 2020
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2021
- Titel
- Vitamin K3 thio-derivative: a novel specific apoptotic inducer in the doxorubicin-sensitive and -resistant cancer cells.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 38
Data source: PubMed
- Beziehungen:
- Property of