Inhibition of epidermal growth factor-induced cell transformation and Akt activation by caffeine.
Mol Carcinog
; 44(1): 67-76, 2005 Sep.
Article
en En
| MEDLINE
| ID: mdl-16044420
ABSTRACT
We found that caffeine significantly inhibited epidermal growth factor (EGF)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation in the JB6 mouse epidermal cell line. The tumor promoter-induced cell transformation was also blocked by treatment with an adenosine A1 receptor antagonist, 8-phenyltheophylline (8-PTH). Caffeine slightly attenuated activation of EGF-induced activator protein 1 (AP-1) activation, which play important roles in cell transformation, but only at the highest concentration examined (1 mM). Interestingly, pretreatment with caffeine suppressed EGF-induced phosphorylation and activation of Akt and ribosomal p 70 S6 protein kinase (p 70 S 6 K), a target of Akt, without inhibiting phosphatidylinositol 3-kinase (PI 3 K) activation. The inhibition of Akt activation of caffeine was not a result of its adenosine receptor antagonism. Because Akt plays a key role in signal transduction pathways leading to cell proliferation and apoptosis, our results provide novel insight into possible mechanisms of the chemotherapeutic effect of caffeine.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cafeína
/
Transformación Celular Neoplásica
/
Proteínas Proto-Oncogénicas
/
Proteínas Serina-Treonina Quinasas
/
Factor de Crecimiento Epidérmico
Límite:
Animals
Idioma:
En
Revista:
Mol Carcinog
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Año:
2005
Tipo del documento:
Article
País de afiliación:
Japón