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Two
Different Mechanisms of Apoptosis Resistance Observed in Interferon-β Induced Apoptosis of Human Glioma Cells
Ryuta Saito, Masaaki Mizuno, Manabu Hatano, Toshihiro
Kumabe, Takashi Yoshimoto, Jun Yoshida
Department
of Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
(R.S., M.H., T.K., T.Y., J.Y); Department of Neurosurgery, Tohoku University
Graduate School of Medicine, Sendai, Japan (R.S.); Department of Molecular
Neurosurgery, Nagoya University Graduate School of Medicine, Nagoya, Japan (M.M.).
Interferon (IFN)-β is known to exert cytostatic or cytocidal effects in
human glioma cells and is widely used in the treatment for gliomas.
However, precise mechanisms of cell death induced by IFN-β are not well
understood.
In this study, the authors investigated the intracellular signal transduction of
IFN-β
in human glioma cells.
The cell death process observed in susceptible cells SK-MG-1 was accompanied by
characteristic morphological changes of apoptosis, processing of caspases, and
DNA fragmentation.
Use of caspase inhibitors confirmed the activation of caspases, however
activated executioner caspase was caspase-7 rather than caspases-3 or -6.
Activation of DNA endonuclease, DNase-γ
was also observed.
Observation of other IFN-β
relatively resistant glioma cells (U251SP, T98G, U251MG, U87MG, SK-AO2) revealed
two different mechanisms of apoptosis resistance.
In contrast to T98G, U87MG, and SK-AO2 which showed no activation of caspases,
surprisingly, all the apoptosis process except DNase-γ
activation was observed in U251SP and U251MG cells.
Collectively, these findings indicate that IFN-β
induced apoptosis in human glioma cells through activation of caspase-7 and
activation of DNase-γ.
The similar activations of caspases were found also in some of the apoptosis
resistant cells.
These findings may help to improve the IFN-β
therapy in near future.
Keywords: apoptosis, caspase, human glioma cells, IFN-β
Copyright ©
2004 Kluwer Academic Publishers.
All rights reserved
Source:
http://journals.kluweronline.com/article.asp?PIPS=5266132
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