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Activation of c-Jun N-terminal kinase 1 and
caspase 3 in the tamoxifen-induced apoptosis of rat glioma cells
Tseng SH, Wang CH, Lin SM, Chen CK, Huang HY, Chen Y
Department of Surgery, National Taiwan University Hospital and
National Taiwan University College of Medicine, 7 Chung-Shan S. Road, 10016,
Taipei, Taiwan.
Purpose. The mechanisms of the antitumor effects of tamoxifen upon
gliomas are still unclear.
In this study, we investigated the role of c-Jun N-terminal kinase-1 (JNK1) and
caspase 3 in the tamoxifen-induced apoptosis of rat glioma cells.
Methods. Glioma cells were treated with tamoxifen,
followed by a cytotoxicity assay to study its effects on the cells, and then a
flow-activated cell sorter (FACS) analysis was performed to analyze the cellular
apoptosis of the glioma cells.
The expression of JNK1 and phospho-specific JNK1 in glioma cells treated with
tamoxifen was investigated by Western blot analysis.
The activity of caspase 3 in glioma cells was analyzed by caspase activity
assay.
Results. Tamoxifen was demonstrated to exert cytotoxic
effects upon and induced apoptosis of the glioma cells in a concentration- and
time-dependent manner (P<0.05).
Western blot analysis demonstrated that tamoxifen increased the expression of
phospho-specific JNK1 in glioma cells, and an increasing concentration of
tamoxifen induced an increasing expression of phospho-specific JNK1.
Four-hour 50-microM tamoxifen treatment increased the expression of
phospho-specific JNK1 to 3.2 times that of the control level in glioma
cells.
Tamoxifen also increased the activity of caspase 3 in glioma cells.
Pretreatment of glioma cells with the antisense oligonucleotide (OGN) of JNK1
immediately prior to tamoxifen treatment suppressed the expression of
phospho-specific JNK1 and the activity of caspase 3.
The apoptosis fraction of glioma cells induced by 4-h treatment with 50 microM
tamoxifen was decreased from 51% to 28% by pretreatment with the antisense OGN
of JNK1 ( P<0.003), and to 20% by pretreatment with caspase 3 inhibitor
(DEVD-CHO) ( P<0.0008).
Conclusions. The results suggest that the
tamoxifen-induced apoptosis of rat glioma cells is related to the activation of
the JNK1/caspase 3 signaling pathway; however, the confirmation of the
occurrence of such activation in vivo needs further investigation.
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14997384
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