Caffeine sensitizes human H358 cell line to p53-mediated apoptosis by inducing mitochondrial translocation and conformational change of BAX protein.
J Biol Chem
; 276(42): 38980-7, 2001 Oct 19.
Article
em En
| MEDLINE
| ID: mdl-11489880
ABSTRACT
The mechanisms involved in p53-mediated cell death remain controversial. In the present study, we investigated this cell death pathway by stably transfecting the p53-null H358 cell line with a tetracycline-dependent wild type p53-expressing vector. Restoration of p53 triggered a G(2)/M cell cycle arrest and enhanced BAX protein expression, without inducing apoptosis or potentiating the cytotoxic effect of etoposide, vincristine, and cis-platinum. Accordingly, overexpression of BAX in H358 cells, through stable transfection of a tetracycline-regulated expression vector, did not induce cell death. Interestingly, the methylxanthine caffeine (4 mm) promoted the translocation of BAX from the cytosol to the mitochondria. In the setting of an overexpression of BAX, caffeine induced a conformational change of the protein and apoptosis. The consequences of caffeine were independent of its cell cycle-related activities. All together, caffeine synergizes with p53 for inducing cell death through a cell cycle-independent mechanism, involving mitochondrial translocation and conformational change of BAX protein.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cafeína
/
Proteínas Proto-Oncogênicas
/
Apoptose
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Estimulantes do Sistema Nervoso Central
/
Mitocôndrias
Limite:
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2001
Tipo de documento:
Article