Premium
Inhibition of epidermal growth factor‐induced cell transformation and Akt activation by caffeine
Author(s) -
Nomura Masaaki,
Ichimatsu Daisuke,
Moritani Shuzo,
Koyama Ichiko,
Dong Zigang,
Yokogawa Koichi,
Miyamoto Kenichi
Publication year - 2005
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20120
Subject(s) - biology , epidermal growth factor , transformation (genetics) , caffeine , microbiology and biotechnology , growth factor , epidermal growth factor receptor , cell growth , protein kinase b , cancer research , pharmacology , endocrinology , signal transduction , biochemistry , receptor , gene
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 p70 S6 protein kinase (p70 S6K), a target of Akt, without inhibiting phosphatidylinositol 3‐kinase (PI3K) 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. © 2005 Wiley‐Liss, Inc.