TY - JOUR
T1 - Two different mechanisms of apoptosis resistance observed in interferon-β induced apoptosis of human glioma cells
AU - Saito, Ryuta
AU - Mizuno, Masaaki
AU - Hatano, Manabu
AU - Kumabe, Toshihiro
AU - Yoshimoto, Takashi
AU - Yoshida, Jun
PY - 2004/5
Y1 - 2004/5
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Caspase
KW - Human glioma cells
KW - IFN-β
UR - http://www.scopus.com/inward/record.url?scp=2942726249&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2942726249&partnerID=8YFLogxK
U2 - 10.1023/B:NEON.0000024217.68738.11
DO - 10.1023/B:NEON.0000024217.68738.11
M3 - Article
C2 - 15164982
AN - SCOPUS:2942726249
VL - 67
SP - 273
EP - 280
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
SN - 0167-594X
IS - 3
ER -