The nuclear receptor constitutive active/androstane receptor arrests DNA-damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase.
Mol Carcinog
; 51(2): 206-12, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-21557330
ABSTRACT
Here, we have demonstrated that xenobiotic activation of the nuclear receptor (CAR, NR1I3) can result in arresting DNA-damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase. Huh7 cells over-expressing CAR were either treated with dimethyl sulfoxide, the CAR activator TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene; androstenol, 16,(5α)-androsten-3α-OL), or repressor androstenol; these treatments were then followed by adriamycin treatment to damage DNA. FACS analysis revealed that CAR-activation by TCPOBOP increased the rate of arrested Huh7 cells at the G2/M phase (4N DNA content) after DNA damage by adriamycin. This increase correlated with the increase of cell viability in TCPOBOP-treated Huh7 cells, as determined by MTT assays. Real-time polymerase chain reaction analysis determined that, as regulated by CAR, the growth arrest and DNA damage-inducible γ (GADD45γ) and Cyclin G2 genes increased and decreased, respectively, as TCPOBOP increased the number of Huh7 cells arrested at the G2/M phase. Thus, the results suggest that CAR regulates cell cycle, increasing G2/M arrest, and delaying the death of DNA-damaged cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dano ao DNA
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Divisão Celular
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Fase G2
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Receptores Citoplasmáticos e Nucleares
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Carcinoma Hepatocelular
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Neoplasias Hepáticas
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article