2011
Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells.
KOLLÁR, Peter, Tomáš BÁRTA, Veronika ZÁVALOVÁ, Karel SMEJKAL, Aleš HAMPL et. al.Základní údaje
Originální název
Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells.
Autoři
KOLLÁR, Peter (703 Slovensko, garant), Tomáš BÁRTA (203 Česká republika, domácí), Veronika ZÁVALOVÁ (203 Česká republika), Karel SMEJKAL (203 Česká republika) a Aleš HAMPL (203 Česká republika, domácí)
Vydání
British Journal of Pharmacology, England, Wiley-Blackwell Publishing, 2011, 0007-1188
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30200 3.2 Clinical medicine
Stát vydavatele
Velká Británie a Severní Irsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 4.409
Kód RIV
RIV/00216224:14110/11:00067270
Organizační jednotka
Lékařská fakulta
UT WoS
000288018100007
Klíčová slova anglicky
flavonoids; antiproliferative effect; CDK2; cyclins; cell cycle regulators
Příznaky
Mezinárodní význam
Změněno: 21. 10. 2013 09:54, Ing. Mgr. Věra Pospíšilíková
Anotace
V originále
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.
Návaznosti
LC06077, projekt VaV |
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MSM0021622430, záměr |
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MUNI/E/0118/2009, interní kód MU |
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