Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon (IFN)-beta 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-beta are not well understood. In this study, the authors investigated the intracellular signal transduction of IFN-beta 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-gamma was also observed. Observation of other IFN-beta 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-gamma activation was observed in U251SP and U251MG cells. Collectively, these findings indicate that IFN-beta induced apoptosis in human glioma cells through activation of caspase-7 and activation of DNase-gamma. The similar activations of caspases were found also in some of the apoptosis resistant cells. These findings may help to improve the IFN-beta therapy in near future.
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PMID:Two different mechanisms of apoptosis resistance observed in interferon-beta induced apoptosis of human glioma cells. 1516 82

Exogenously added human interferon-beta (HuIFN-beta) protein possesses a remarkable antiproliferative activity in human glioma and melanoma. Endogenous HuIFN-beta protein, which is produced by its gene transfer using cationic liposomes, has much more effective antiproliferative activity against these tumors, even in cells resistant to exogenously added HuIFN-beta protein. As the first step to elucidate the possible difference in antiproliferative mechanisms between exogenous and endogenous HuIFN-beta protein, we here investigated the relationship between the intracellular level of its mRNA and susceptibility to exogenously added HuIFN-beta protein. In this study, we used seven human glioma cell lines (SK-MG-1, SK-MG-4, SK-AO2, U87MG, U251SP, U251MG and T98) and one human melanoma cell line (MMAN). At first, we examined the relationship between spontaneous expression of HuIFN-beta mRNA and susceptibility to exogenously added HuIFN-beta protein (50 IU/ml) in human glioma cells and then confirmed a significant correlation between them. Next, we confirmed that administration of 0-100 IU/ml exogenously added HuIFN-beta protein upregulated the HuIFN-beta mRNA in a dose-dependent manner using the RT-PCR technique and that the HuIFN-beta mRNA was suppressed by siRNA for HuIFN-beta in SK-MG-1 and MMAN cells. Furthermore, we confirmed that the siRNA for HuIFN-beta significantly suppressed the antiproliferative effect of SK-MG-1 cells treated with 10-100 IU/ml HuIFN-beta protein and MMAN cells with 25 and 50 IU/ml HuIFN-beta protein. We found this phenomenon in another human glioma cell line, U87MG cells, as well. This finding would suggest that susceptibility to exogenously added HuIFN-beta protein is related to the amount of intracellular HuIFN-beta mRNA in human glioma and melanoma cells.
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PMID:Susceptibility to exogenously added interferon-beta protein depends on intracellular interferon-beta mRNA level in human glioma cells. 1634 29