TY - JOUR
T1 - Involvement of up-regulation of PUMA in non-steroidal anti-inflammatory drug-induced apoptosis
AU - Ishihara, Tomoaki
AU - Hoshino, Tatsuya
AU - Namba, Takushi
AU - Tanaka, Ken ichiro
AU - Mizushima, Tohru
N1 - Funding Information:
This work was supported by the Japan Science and Technology Agency.
PY - 2007/5/11
Y1 - 2007/5/11
N2 - 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.
AB - 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.
KW - ATF4
KW - Apoptosis
KW - CHOP
KW - Endoplasmic reticulum
KW - PUMA
UR - http://www.scopus.com/inward/record.url?scp=33947668865&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947668865&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2007.03.034
DO - 10.1016/j.bbrc.2007.03.034
M3 - Article
C2 - 17368424
AN - SCOPUS:33947668865
SN - 0006-291X
VL - 356
SP - 711
EP - 717
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
