@article{oai:kanazawa-u.repo.nii.ac.jp:00026627, author = {Nomura, Masaaki and Ichimatsu, Daisuke and Moritani, Shuzo and Koyama, Ichiko and Dong, Zigang and Yokogawa, Koichi and Miyamoto, Kenichi}, issue = {1}, journal = {Molecular Carcinogenesis}, month = {Sep}, note = {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., 金沢大学医学部附属病院薬剤部}, pages = {67--76}, title = {Inhibition of epidermal growth factor-induced cell transformation and Akt activation by caffeine}, volume = {44}, year = {2005} }