Miltirone Induces G2/M Cell Cycle Arrest and Apoptosis in CCRF-CEM Acute Lymphoblastic Leukemia Cells
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Ching-Fen Wu
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000357138300020&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1021/acs.jnatprod.5b00158
- eISSN
- 1520-6025
- Externe Identifier
- Clarivate Analytics Document Solution ID: CL7FQ
- PubMed Identifier: 26035463
- ISSN
- 0163-3864
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- JOURNAL OF NATURAL PRODUCTS
- Paginierung
- 1339 - 1347
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Titel
- Miltirone Induces G2/M Cell Cycle Arrest and Apoptosis in CCRF-CEM Acute Lymphoblastic Leukemia Cells
- Sub types
- Article
- Ausgabe der Zeitschrift
- 78
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Autoren
- Ching-Fen Wu
- Thomas Efferth
- DOI
- 10.1021/acs.jnatprod.5b00158
- eISSN
- 1520-6025
- ISSN
- 0163-3864
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Journal of Natural Products
- Sprache
- en
- Online publication date
- 2015
- Paginierung
- 1339 - 1347
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Herausgeber
- American Chemical Society (ACS)
- Herausgeber URL
- http://dx.doi.org/10.1021/acs.jnatprod.5b00158
- Datum der Datenerfassung
- 2023
- Titel
- Miltirone Induces G2/M Cell Cycle Arrest and Apoptosis in CCRF-CEM Acute Lymphoblastic Leukemia Cells
- Ausgabe der Zeitschrift
- 78
Datenquelle: Crossref
- Abstract
- Miltirone (1) is a diterpene quinone extracted from a well-known Chinese traditional herb (Salvia miltiorrhiza). We investigated the cytotoxic effects of miltirone toward sensitive and multidrug-resistant acute lymphoblastic leukemia cell lines. Miltirone inhibited multidrug-resistant P-glycoprotein (P-gp)-overexpressing CEM/ADR5000 cells better than drug-sensitive CCRF-CEM wild-type cells, a phenomenon termed collateral sensitivity. Flow cytometric analyses revealed that miltirone induced G2/M arrest and apoptosis. Furthermore, miltirone stimulated reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) disruption, which in turn induced DNA damage and activation of caspases and poly ADP-ribose polymerase (PARP). Downregulation of CCNB1 (cyclin B1) and CDC2 mRNA and upregulation of CDKN1A (p21) mRNA were in accord with miltirone-induced G2/M arrest. Moreover, miltirone decreased cell adherence to fibronectin. Molecular docking revealed that miltirone bound to the ATP-binding site of IKK-β. In conclusion, miltirone was collateral sensitive in multidrug-resistant P-gp-overexpressing cells, induced G2/M arrest, and triggered apoptosis via ROS-generated breakdown of MMP and DNA damage. Therefore, miltirone may be a promising candidate for cancer chemotherapy.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz 55128, Germany.
- Autoren
- Ching-Fen Wu
- Thomas Efferth
- Thomas Efferth
- DOI
- 10.1021/acs.jnatprod.5b00158
- eISSN
- 1520-6025
- Externe Identifier
- PubMed Identifier: 26035463
- Funding acknowledgements
- National Science Council Taiwan:
- German Academic Exchange Service:
- Open access
- false
- ISSN
- 0163-3864
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Journal of natural products
- Schlüsselwörter
- Humans
- Salvia miltiorrhiza
- Reactive Oxygen Species
- Phenanthrenes
- Caspases
- Apoptosis
- Molecular Structure
- Cyclin-Dependent Kinase Inhibitor p21
- Membrane Potential, Mitochondrial
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- G2 Phase Cell Cycle Checkpoints
- ATP Binding Cassette Transporter, Subfamily B
- Sprache
- eng
- Medium
- Print-Electronic
- Online publication date
- 2015
- Paginierung
- 1339 - 1347
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum der Datenerfassung
- 2015
- Titel
- Miltirone Induces G2/M Cell Cycle Arrest and Apoptosis in CCRF-CEM Acute Lymphoblastic Leukemia Cells.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 78
Datenquelle: Europe PubMed Central
- Abstract
- Miltirone (1) is a diterpene quinone extracted from a well-known Chinese traditional herb (Salvia miltiorrhiza). We investigated the cytotoxic effects of miltirone toward sensitive and multidrug-resistant acute lymphoblastic leukemia cell lines. Miltirone inhibited multidrug-resistant P-glycoprotein (P-gp)-overexpressing CEM/ADR5000 cells better than drug-sensitive CCRF-CEM wild-type cells, a phenomenon termed collateral sensitivity. Flow cytometric analyses revealed that miltirone induced G2/M arrest and apoptosis. Furthermore, miltirone stimulated reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) disruption, which in turn induced DNA damage and activation of caspases and poly ADP-ribose polymerase (PARP). Downregulation of CCNB1 (cyclin B1) and CDC2 mRNA and upregulation of CDKN1A (p21) mRNA were in accord with miltirone-induced G2/M arrest. Moreover, miltirone decreased cell adherence to fibronectin. Molecular docking revealed that miltirone bound to the ATP-binding site of IKK-β. In conclusion, miltirone was collateral sensitive in multidrug-resistant P-gp-overexpressing cells, induced G2/M arrest, and triggered apoptosis via ROS-generated breakdown of MMP and DNA damage. Therefore, miltirone may be a promising candidate for cancer chemotherapy.
- Autoren
- Ching-Fen Wu
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/26035463
- DOI
- 10.1021/acs.jnatprod.5b00158
- eISSN
- 1520-6025
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- J Nat Prod
- Schlüsselwörter
- ATP Binding Cassette Transporter, Subfamily B
- Apoptosis
- Caspases
- Cyclin-Dependent Kinase Inhibitor p21
- G2 Phase Cell Cycle Checkpoints
- Humans
- Membrane Potential, Mitochondrial
- Molecular Structure
- Phenanthrenes
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Reactive Oxygen Species
- Salvia miltiorrhiza
- Sprache
- eng
- Country
- United States
- Paginierung
- 1339 - 1347
- Datum der Veröffentlichung
- 2015
- Status
- Published
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2015
- Titel
- Miltirone Induces G2/M Cell Cycle Arrest and Apoptosis in CCRF-CEM Acute Lymphoblastic Leukemia Cells.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 78
Datenquelle: PubMed
- Beziehungen:
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