Caffeine induces TP53-independent G1-phase arrest and apoptosis in human lung tumor cells in a dose-dependent manner

Wenqing Qi, Dianhua Qiao, Jesse D Martinez

Research output: Contribution to journalArticle

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Abstract

Caffeine is a model radiosensitizing agent that is thought to work by abrogating the radiation-induced G2-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 G2-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 G1-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.

Original languageEnglish (US)
Pages (from-to)166-174
Number of pages9
JournalRadiation Research
Volume157
Issue number2
StatePublished - 2002

Fingerprint

caffeine
G1 Phase
apoptosis
lung neoplasms
Caffeine
interphase
lungs
tumors
Apoptosis
dosage
Lung
Neoplasms
cyclin-dependent kinase
Cyclin-Dependent Kinases
Cell Cycle Checkpoints
G2 Phase Cell Cycle Checkpoints
Radiation
Radiation-Sensitizing Agents
neoplasm cells
phosphorylation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Caffeine induces TP53-independent G1-phase arrest and apoptosis in human lung tumor cells in a dose-dependent manner. / Qi, Wenqing; Qiao, Dianhua; Martinez, Jesse D.

In: Radiation Research, Vol. 157, No. 2, 2002, p. 166-174.

Research output: Contribution to journalArticle

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AB - Caffeine is a model radiosensitizing agent that is thought to work by abrogating the radiation-induced G2-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 G2-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 G1-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.

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