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@article{931516,
author = {Kollár, Peter and Bárta, Tomáš and Závalová, Veronika and Smejkal, Karel and Hampl, Aleš},
article_location = {England},
article_number = {7},
doi = {http://dx.doi.org/10.1111/j.1476-5381.2010.01171.x},
keywords = {flavonoids; antiproliferative effect; CDK2; cyclins; cell cycle regulators},
language = {eng},
issn = {0007-1188},
journal = {British Journal of Pharmacology},
title = {Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells.},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21175584},
volume = {162},
year = {2011}
}
TY - JOUR
ID - 931516
AU - Kollár, Peter - Bárta, Tomáš - Závalová, Veronika - Smejkal, Karel - Hampl, Aleš
PY - 2011
TI - Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells.
JF - British Journal of Pharmacology
VL - 162
IS - 7
SP - 1534-1541
EP - 1534-1541
PB - Wiley-Blackwell Publishing
SN - 00071188
KW - flavonoids
KW - antiproliferative effect
KW - CDK2
KW - cyclins
KW - cell cycle regulators
UR - http://www.ncbi.nlm.nih.gov/pubmed/21175584
N2 - 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 mu M, but inhibited cell growth in a dose-dependent manner at concentrations of 5 mu M 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 (gamma-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.
ER -
KOLLÁR, Peter, Tomáš BÁRTA, Veronika ZÁVALOVÁ, Karel SMEJKAL a Aleš HAMPL. Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells. \textit{British Journal of Pharmacology}. England: Wiley-Blackwell Publishing, 2011, roč.~162, č.~7, s.~1534-1541. ISSN~0007-1188. Dostupné z: https://dx.doi.org/10.1111/j.1476-5381.2010.01171.x.
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