Caffeine induces TP53-independent G(1)-phase arrest and apoptosis in human lung tumor cells in a dose-dependent manner.

Abstract:

:Caffeine is a model radiosensitizing agent that is thought to work by abrogating the radiation-induced G(2)-phase checkpoint. In this study, we examined the effect that various concentrations of caffeine had on cell cycle checkpoints and apoptosis in cells of a human lung carcinoma cell line and found that a concentration of 0.5 mM caffeine could abrogate the G(2)-phase arrest normally seen after exposure to ionizing radiation. Surprisingly, at a concentration of 5 mM, caffeine not only induced apoptosis by itself and acted synergistically to enhance radiation-induced apoptosis, but also induced a TP53-independent G(1)-phase arrest. Examination of the molecular mechanisms by which caffeine produced these effects revealed that caffeine had opposing effects on different cyclin-dependent kinases. CDK2 activity was suppressed by caffeine, whereas activity of CDC2 was enhanced by suppressing phosphorylation on Tyr15 and by interfering with 14-3-3 binding to CDC25C. These data indicate that the effect of caffeine on cell cycle checkpoints and apoptosis is dependent on dose and that caffeine acts through differential regulation of cyclin-dependent kinase activity.

journal_name

Radiat Res

journal_title

Radiation research

authors

Qi W,Qiao D,Martinez JD

doi

10.1667/0033-7587(2002)157[0166:citigp]2.0.co;2

subject

Has Abstract

pub_date

2002-02-01 00:00:00

pages

166-74

issue

2

eissn

0033-7587

issn

1938-5404

journal_volume

157

pub_type

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