Inhibition of epidermal growth factor-induced cell transformation and Akt activation by caffeine.

Autor: Nomura M; Department of Hospital Pharmacy, School of Medicine, Kanazawa University, Kanazawa, Japan., Ichimatsu D, Moritani S, Koyama I, Dong Z, Yokogawa K, Miyamoto K
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2005 Sep; Vol. 44 (1), pp. 67-76.
DOI: 10.1002/mc.20120
Abstrakt: 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.
((c) 2005 Wiley-Liss, Inc.)
Databáze: MEDLINE
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