Caffeine induces G2/M arrest and apoptosis via a novel p53-dependent pathway in NB4 promyelocytic leukemia cells

Keisuke Ito, Tomonori Nakazato, Yoshitaka Miyakawa, Kenji Yamato, Yasuo Ikeda, Masahiro Kizaki

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Methylxantine derivative, caffeine, is known to prevent the p53-dependent apoptosis pathway via inhibition of ATM (ataxia telangiectasia mutated) kinase, which activates p53 by phosphorylation of the Ser-15 residue. In contrast, it has been reported that caffeine induces p53-mediated apoptosis through Bax protein in non-small-cell lung cancer cells. Therefore, the effects of caffeine on cellular growth in malignant cells are controversial. We investigated the effects of caffeine on cell proliferation, cell cycle progression, and induction of apoptosis in NB4 promyelocytic leukemia cells containing wild-type p53. Caffeine suppressed the cellular growth of NB4 cells in a dose- and time-dependent manner. Caffeine induced G2/M phase cell cycle arrest in NB4 cells in association with the induction of phosphorylation at the Ser-15 residue of p53 and induction of tyrosine phosphorylation of cdc2. Expression of Bax protein was increased in NB4 cells after treatment with caffeine. Interestingly, the antisense oligonucleotides for p53 significantly reduced p53 expression and caffeine-induced G2/M phase cell cycle arrest in NB4 cells. These results suggest that caffeine induces cell cycle arrest and apoptosis in association with activation of p53 by a novel pathway to phosphorylate the Ser-15 residue and induction of phosphorylation of cdc 2 in leukemic cells with normal p53.

Original languageEnglish (US)
Pages (from-to)276-283
Number of pages8
JournalJournal of Cellular Physiology
Volume196
Issue number2
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

Fingerprint

Caffeine
Leukemia
Apoptosis
Phosphorylation
Cells
M Phase Cell Cycle Checkpoints
bcl-2-Associated X Protein
G2 Phase
Association reactions
Ataxia Telangiectasia
Antisense Oligonucleotides
Cell proliferation
Growth
Cell Cycle Checkpoints
Non-Small Cell Lung Carcinoma
Tyrosine
Cell Cycle
Phosphotransferases
Chemical activation
Cell Proliferation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Caffeine induces G2/M arrest and apoptosis via a novel p53-dependent pathway in NB4 promyelocytic leukemia cells. / Ito, Keisuke; Nakazato, Tomonori; Miyakawa, Yoshitaka; Yamato, Kenji; Ikeda, Yasuo; Kizaki, Masahiro.

In: Journal of Cellular Physiology, Vol. 196, No. 2, 01.08.2003, p. 276-283.

Research output: Contribution to journalArticle

Ito, Keisuke ; Nakazato, Tomonori ; Miyakawa, Yoshitaka ; Yamato, Kenji ; Ikeda, Yasuo ; Kizaki, Masahiro. / Caffeine induces G2/M arrest and apoptosis via a novel p53-dependent pathway in NB4 promyelocytic leukemia cells. In: Journal of Cellular Physiology. 2003 ; Vol. 196, No. 2. pp. 276-283.
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