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

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.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Nomura M,Ichimatsu D,Moritani S,Koyama I,Dong Z,Yokogawa K,Miyamoto K

doi

10.1002/mc.20120

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

67-76

issue

1

eissn

0899-1987

issn

1098-2744

journal_volume

44

pub_type

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