Document Detail


Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells.
MedLine Citation:
PMID:  21175584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Paulownia tomentosa is a rich source of geranylated flavanones, some of which we have previously shown to have cytotoxic activity. To identify members of this class of compounds with cytostatic effects, we assessed the effects of the geranylated flavanone tomentodiplacone B (TOM B) on cell cycle progression and cell cycle regulatory pathways of THP-1 human monocytic leukaemia cells.
EXPERIMENTAL APPROACH: Cell viability was measured by dye exclusion and proliferation by WST-1 assays; cell cycle was monitored by flow cytometry. Regulatory proteins were assessed by immunoprecipitation and kinase assays, and Western blotting.
KEY RESULTS: Tomentodiplacone B had no effect during the first 24 h of cell growth at concentrations between 1 and 2.5 µM, but inhibited cell growth in a dose-dependent manner at concentrations of 5 µM or higher. Growth inhibition during the first 24 h of exposure to TOM B was not accompanied by cytotoxicity as cells were accumulated in G1 phase dose-dependently. This G1 phase accumulation was associated with down-regulation of cyclin-dependent kinase 2 activity and also protein levels of cyclins E1 and A2. However, key stress-related molecules (γ-H2AX, p53 and p21) were not induced, suggesting that TOM B acts by directly inhibiting the cyclin-dependent kinase 2 signalling pathway rather than initiating DNA damage or cellular stress.
CONCLUSIONS AND IMPLICATIONS: Our study provides the first evidence that TOM B directly inhibits proliferation of human monocytic leukaemia cells, and thus is a potential anticancer agent, preventing leukaemia cells from progressing from G1 phase into DNA synthesis.
Authors:
Peter Kollár; Tomáš Bárta; Veronika Závalová; Karel Smejkal; Aleš Hampl
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  162     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-07     Completed Date:  2011-07-12     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1534-41     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Department of Human Pharmacology and Toxicology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno, Czech Republic. kollarp@vfu.cz
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MeSH Terms
Descriptor/Qualifier:
Anticarcinogenic Agents / pharmacology
Cell Line, Tumor
Cell Proliferation / drug effects
Cyclin D / metabolism
Cyclin-Dependent Kinase 2 / antagonists & inhibitors,  biosynthesis,  metabolism
Cyclins / metabolism
Down-Regulation / drug effects
Flavanones / pharmacology*
G1 Phase / drug effects
Humans
Leukemia, Monocytic, Acute
Monocytes / cytology,  drug effects*,  metabolism
Monoterpenes / pharmacology*
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Cyclin D; 0/Cyclins; 0/Flavanones; 0/Monoterpenes; 0/tomentodiplacone B; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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