Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells.

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Publikace nespadá pod Ekonomicko-správní fakultu, ale pod Lékařskou fakultu. Oficiální stránka publikace je na webu muni.cz.
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KOLLÁR Peter BÁRTA Tomáš ZÁVALOVÁ Veronika SMEJKAL Karel HAMPL Aleš

Rok publikování 2011
Druh Článek v odborném periodiku
Časopis / Zdroj British Journal of Pharmacology
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
www http://www.ncbi.nlm.nih.gov/pubmed/21175584
Doi http://dx.doi.org/10.1111/j.1476-5381.2010.01171.x
Obor Onkologie a hematologie
Klíčová slova flavonoids; antiproliferative effect; CDK2; cyclins; cell cycle regulators
Popis 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.
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