Involvement of up-regulation of PUMA in non-steroidal anti-inflammatory drug-induced apoptosis

Tomoaki Ishihara, Tatsuya Hoshino, Takushi Namba, Ken ichiro Tanaka, Tohru Mizushima

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

NSAIDs such as celecoxib induce apoptosis in cancer cells. Although this apoptotic effect is involved in the anti-tumor activity associated with such drugs, the mechanism by which this occurs is not fully understood. We report here that various NSAIDs, including celecoxib, up-regulate PUMA, a Bcl-2 family protein with potent apoptosis-inducing activity, in human gastric carcinoma cell line, accompanying the induction of apoptosis. Experiments using siRNA and an intracellular Ca2+ chelator revealed that Ca2+-dependent up-regulation of ATF4 and CHOP is involved in this up-regulation of PUMA. The siRNA for PUMA inhibited the celecoxib-induced activation and translocation of Bax, release of cytochrome c into the cytosol and induction of apoptosis, suggesting that PUMA plays an important role in celecoxib-induced mitochondrial dysfunction and the resulting apoptosis.

Original languageEnglish
Pages (from-to)711-717
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume356
Issue number3
DOIs
Publication statusPublished - 2007 May 11

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Keywords

  • ATF4
  • Apoptosis
  • CHOP
  • Endoplasmic reticulum
  • PUMA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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