Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells

Publication type:
Journal article
Metadata:
Autoren
  • Ching-Fen Wu
  • Ean-Jeong Seo
  • Sabine M Klauck
  • Thomas Efferth
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000371144200010&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2015.12.011
Externe Identifier
  • Clarivate Analytics Document Solution ID: DF2BL
  • PubMed Identifier: 26926179
ISSN
0944-7113
Ausgabe der Veröffentlichung
2
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Salvia miltiorrhiza Bunge (Lamiaceae)
  • Cryptotanshinone
  • Pharmacogenetics
  • DDIT3
  • Unfolded protein response (UPR)
  • Eukaryotic initiation factor (eIf)
Paginierung
174 - 180
Datum der Veröffentlichung
2016
Status
Published
Titel
Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells
Sub types
  • Article
Ausgabe der Zeitschrift
23

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Ching-Fen Wu
  • Ean-Jeong Seo
  • Sabine M Klauck
  • Thomas Efferth
DOI
10.1016/j.phymed.2015.12.011
ISSN
0944-7113
Ausgabe der Veröffentlichung
2
Zeitschrift
Phytomedicine
Sprache
en
Paginierung
174 - 180
Datum der Veröffentlichung
2016
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2015.12.011
Datum der Datenerfassung
2018
Titel
Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells
Ausgabe der Zeitschrift
23

Data source: Crossref

Abstract
<h4>Background</h4>Unfolded protein responses (UPR) determine cell fate and are recognized as anticancer targets. In a previous research, we reported that cryptotanshinone (CPT) exerted cytotoxic effects toward acute lymphoblastic leukemia cells through mitochondria-mediated apoptosis.<h4>Purpose</h4>In the present study, we further investigated the role of UPR in CPT-induced cytotoxicity on acute lymphoblastic leukemia cells by applying tools of pharmacogenomics and bioinformatics.<h4>Methods</h4>Gene expression profiling was performed by mRNA microarray hybridization. Potential transcription factor binding motifs were identified in the promoter regions of the deregulated genes by Cistrome software. Molecular docking on eIF-4A and PI3K was performed to investigate the inhibitory activity of CPT on translation initiation.<h4>Results</h4>CPT regulated genes related to UPR and eIF2 signaling pathways. The DNA-Damage-Inducible Transcript 3 (DDIT3) gene, which is activated as consequence of UPR malfunction during apoptosis, was induced and validated by in vitro experiments. Transcription factor binding motif analysis of the microarrary-retrieved deregulated genes in the promoter region emphasized the relevance of transcription factors, such as ATF2, ATF4 and XBP1, regulating UPR and cell apoptosis. Molecular docking suggested inhibitory effects of CPT by binding to eIF-4A and PI3K providing evidence for a role of CPT's in the disruption of protein synthesis.<h4>Conclusion</h4>CPT triggered UPR and inhibited protein synthesis via eIF-mediated translation initiation, potentially supporting CPT-induced cytotoxic effects toward acute leukemia cells.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Autoren
  • Ching-Fen Wu
  • Ean-Jeong Seo
  • Sabine M Klauck
  • Thomas Efferth
  • Thomas Efferth
DOI
10.1016/j.phymed.2015.12.011
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 26926179
Open access
false
ISSN
0944-7113
Ausgabe der Veröffentlichung
2
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Cell Line, Tumor
  • Humans
  • Phenanthrenes
  • Eukaryotic Initiation Factor-4A
  • Eukaryotic Initiation Factors
  • Eukaryotic Initiation Factor-2
  • Transcription Factors
  • RNA, Messenger
  • Computational Biology
  • Pharmacogenetics
  • Signal Transduction
  • Apoptosis
  • Transcription Factor CHOP
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Unfolded Protein Response
  • Phosphatidylinositol 3-Kinases
  • Molecular Docking Simulation
Sprache
eng
Medium
Print-Electronic
Online publication date
2016
Paginierung
174 - 180
Datum der Veröffentlichung
2016
Status
Published
Datum der Datenerfassung
2016
Titel
Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
23

Data source: Europe PubMed Central

Abstract
BACKGROUND: Unfolded protein responses (UPR) determine cell fate and are recognized as anticancer targets. In a previous research, we reported that cryptotanshinone (CPT) exerted cytotoxic effects toward acute lymphoblastic leukemia cells through mitochondria-mediated apoptosis. PURPOSE: In the present study, we further investigated the role of UPR in CPT-induced cytotoxicity on acute lymphoblastic leukemia cells by applying tools of pharmacogenomics and bioinformatics. METHODS: Gene expression profiling was performed by mRNA microarray hybridization. Potential transcription factor binding motifs were identified in the promoter regions of the deregulated genes by Cistrome software. Molecular docking on eIF-4A and PI3K was performed to investigate the inhibitory activity of CPT on translation initiation. RESULTS: CPT regulated genes related to UPR and eIF2 signaling pathways. The DNA-Damage-Inducible Transcript 3 (DDIT3) gene, which is activated as consequence of UPR malfunction during apoptosis, was induced and validated by in vitro experiments. Transcription factor binding motif analysis of the microarrary-retrieved deregulated genes in the promoter region emphasized the relevance of transcription factors, such as ATF2, ATF4 and XBP1, regulating UPR and cell apoptosis. Molecular docking suggested inhibitory effects of CPT by binding to eIF-4A and PI3K providing evidence for a role of CPT's in the disruption of protein synthesis. CONCLUSION: CPT triggered UPR and inhibited protein synthesis via eIF-mediated translation initiation, potentially supporting CPT-induced cytotoxic effects toward acute leukemia cells.
Date of acceptance
2015
Autoren
  • Ching-Fen Wu
  • Ean-Jeong Seo
  • Sabine M Klauck
  • Thomas Efferth
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/26926179
DOI
10.1016/j.phymed.2015.12.011
eISSN
1618-095X
Ausgabe der Veröffentlichung
2
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Cryptotanshinone
  • DDIT3
  • Eukaryotic initiation factor (eIF)
  • Pharmacogenetics
  • Salvia miltiorrhiza Bunge (Lamiaceae)
  • Unfolded protein response (UPR)
  • Apoptosis
  • Cell Line, Tumor
  • Computational Biology
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-4A
  • Eukaryotic Initiation Factors
  • Humans
  • Molecular Docking Simulation
  • Pharmacogenetics
  • Phenanthrenes
  • Phosphatidylinositol 3-Kinases
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • RNA, Messenger
  • Signal Transduction
  • Transcription Factor CHOP
  • Transcription Factors
  • Unfolded Protein Response
Sprache
eng
Country
Germany
Paginierung
174 - 180
PII
S0944-7113(15)00385-2
Datum der Veröffentlichung
2016
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2016
Titel
Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
23

Data source: PubMed

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