Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells

Publication type:
Journal article
Metadata:
Autoren
  • Ching-Fen Wu
  • Sabine M Klauck
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000385653000015&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1007/s00204-015-1616-4
eISSN
1432-0738
Externe Identifier
  • Clarivate Analytics Document Solution ID: DZ2DR
  • PubMed Identifier: 26564229
ISSN
0340-5761
Ausgabe der Veröffentlichung
9
Zeitschrift
ARCHIVES OF TOXICOLOGY
Schlüsselwörter
  • Salvia miltiorrhiza Bunge (Lamiaceae)
  • Cryptotanshinone
  • Pharmacogenetics
  • Molecular docking
  • Cancer
  • Multidrug resistance
Paginierung
2275 - 2286
Datum der Veröffentlichung
2016
Status
Published
Titel
Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells
Sub types
  • Article
Ausgabe der Zeitschrift
90

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Ching-Fen Wu
  • Sabine M Klauck
  • Thomas Efferth
DOI
10.1007/s00204-015-1616-4
eISSN
1432-0738
ISSN
0340-5761
Ausgabe der Veröffentlichung
9
Zeitschrift
Archives of Toxicology
Sprache
en
Online publication date
2015
Paginierung
2275 - 2286
Datum der Veröffentlichung
2016
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1007/s00204-015-1616-4
Datum der Datenerfassung
2019
Titel
Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells
Ausgabe der Zeitschrift
90

Data source: Crossref

Abstract
Cryptotanshinone, a well-known diterpene quinone from a widely used traditional Chinese herb named Salvia miltiorrhiza, has been reported for its therapeutical potentials on diverse activities. In this study, pharmacological effects of cryptotanshinone on acute lymphoblastic leukemia cells were investigated. IC50 values of 5.0 and 4.8 were obtained in CEM/ADR5000 and CCRF-CEM. Microarray-based mRNA expression revealed that cryptotanshinone regulated genes associated with cell cycle, DNA damage, reactive oxygen species (ROS), NFκB signaling and cellular movement. The involvement of these pathways in the mode of action of cryptotanshinone was subsequently validated by additional independent in vitro studies. Cryptotanshinone stimulated ROS generation and induced DNA damage. It arrested cells in G2/M phase of the cell cycle and induced apoptosis as measured by annexin V-FITC-conjugating fluorescence. The induction of the intrinsic apoptotic pathway by cryptotanshinone was proved by loss of mitochondrial membrane potential and increased cleavage of caspase 3/7, caspase 9 and poly ADP ribose polymerase (PARP). DNA-binding motif analysis of the microarray-retrieved deregulated genes in the promoter region revealed NFκB as potential transcription factor involved in cryptotanshinone's mode of action. Molecular docking and Western blotting provided supportive evidence, suggesting that cryptotanshinone binds to IKK-β and inhibits the translocation of p65 from the cytosol to the nucleus. In addition, cryptotanshinone inhibited cellular movement as shown by a fibronectin-based cellular adhesion assay, indicating that this compound exerts anti-invasive features. In conclusion, cryptotanshinone exerts profound cytotoxicity, which is caused by multispecific modes of actions, including G2/M arrest, apoptosis and inhibition of cellular movement. The inhibitory activities of this compound may be explained by inhibition of NFκB, which orchestrates all these mechanisms.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128, Mainz, Germany.
Autoren
DOI
10.1007/s00204-015-1616-4
eISSN
1432-0738
Externe Identifier
  • PubMed Identifier: 26564229
Funding acknowledgements
  • German Academic Exchange Service:
  • National Science Council Taiwan:
Open access
false
ISSN
0340-5761
Ausgabe der Veröffentlichung
9
Zeitschrift
Archives of toxicology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • DNA Damage
  • Reactive Oxygen Species
  • Phenanthrenes
  • Cell Cycle Proteins
  • NF-kappa B
  • Antineoplastic Agents, Phytogenic
  • Oligonucleotide Array Sequence Analysis
  • Gene Expression Profiling
  • Inhibitory Concentration 50
  • Cell Adhesion
  • Signal Transduction
  • Apoptosis
  • Cell Movement
  • Cell Survival
  • Gene Expression Regulation, Neoplastic
  • Dose-Response Relationship, Drug
  • Apoptosis Regulatory Proteins
  • Membrane Potential, Mitochondrial
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • G2 Phase Cell Cycle Checkpoints
  • Molecular Docking Simulation
Sprache
eng
Medium
Print-Electronic
Online publication date
2015
Paginierung
2275 - 2286
Datum der Veröffentlichung
2016
Status
Published
Datum der Datenerfassung
2015
Titel
Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
90

Data source: Europe PubMed Central

Abstract
Cryptotanshinone, a well-known diterpene quinone from a widely used traditional Chinese herb named Salvia miltiorrhiza, has been reported for its therapeutical potentials on diverse activities. In this study, pharmacological effects of cryptotanshinone on acute lymphoblastic leukemia cells were investigated. IC50 values of 5.0 and 4.8 were obtained in CEM/ADR5000 and CCRF-CEM. Microarray-based mRNA expression revealed that cryptotanshinone regulated genes associated with cell cycle, DNA damage, reactive oxygen species (ROS), NFκB signaling and cellular movement. The involvement of these pathways in the mode of action of cryptotanshinone was subsequently validated by additional independent in vitro studies. Cryptotanshinone stimulated ROS generation and induced DNA damage. It arrested cells in G2/M phase of the cell cycle and induced apoptosis as measured by annexin V-FITC-conjugating fluorescence. The induction of the intrinsic apoptotic pathway by cryptotanshinone was proved by loss of mitochondrial membrane potential and increased cleavage of caspase 3/7, caspase 9 and poly ADP ribose polymerase (PARP). DNA-binding motif analysis of the microarray-retrieved deregulated genes in the promoter region revealed NFκB as potential transcription factor involved in cryptotanshinone's mode of action. Molecular docking and Western blotting provided supportive evidence, suggesting that cryptotanshinone binds to IKK-β and inhibits the translocation of p65 from the cytosol to the nucleus. In addition, cryptotanshinone inhibited cellular movement as shown by a fibronectin-based cellular adhesion assay, indicating that this compound exerts anti-invasive features. In conclusion, cryptotanshinone exerts profound cytotoxicity, which is caused by multispecific modes of actions, including G2/M arrest, apoptosis and inhibition of cellular movement. The inhibitory activities of this compound may be explained by inhibition of NFκB, which orchestrates all these mechanisms.
Date of acceptance
2015
Autoren
  • Ching-Fen Wu
  • Sabine M Klauck
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/26564229
DOI
10.1007/s00204-015-1616-4
eISSN
1432-0738
Ausgabe der Veröffentlichung
9
Zeitschrift
Arch Toxicol
Schlüsselwörter
  • Cancer
  • Cryptotanshinone
  • Molecular docking
  • Multidrug resistance
  • Pharmacogenetics
  • Salvia miltiorrhiza Bunge (Lamiaceae)
  • Antineoplastic Agents, Phytogenic
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Cell Adhesion
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Movement
  • Cell Survival
  • DNA Damage
  • Dose-Response Relationship, Drug
  • G2 Phase Cell Cycle Checkpoints
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitory Concentration 50
  • Membrane Potential, Mitochondrial
  • Molecular Docking Simulation
  • NF-kappa B
  • Oligonucleotide Array Sequence Analysis
  • Phenanthrenes
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Reactive Oxygen Species
  • Signal Transduction
Sprache
eng
Country
Germany
Paginierung
2275 - 2286
PII
10.1007/s00204-015-1616-4
Datum der Veröffentlichung
2016
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2017
Titel
Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
90

Data source: PubMed

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