Ribozyme inhibition of the protein kinase C alpha triggers apoptosis in glioma cells.
Although protein kinase C has been shown to be involved in a wide range of biological functions, the precise role of each isoform in a specific cell function remains to be clarified. Here we demonstrate that a ribozyme specific for the human protein kinase C alpha (PKC alpha), a classical PKC isoform, induces cell death in glioma cell lines. This cell death was identified as apoptosis by morphologic alterations and endonucleosomal DNA fragmentation. The inhibition of PKC alpha gene expression by the ribozyme resulted in a significant reduction in Bcl-xL gene expression, a protein that inhibits apoptosis and is overexpressed in glioma cells. Taken together, our data suggest that the PKC alpha ribozymes are a potent inducer of apoptosis in glioma cells, which may act through suppressing Bcl-xL gene expression and/or activity. PKC alpha ribozymes may prove useful in the management of malignant gliomas.
Leirdal
M
M
Institute for Cancer Research, Department of Immunology, The Norwegian Radium Hospital, Oslo.
Sioud
M
M
D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000235:genetics; D051571:Protein Kinase C-alpha; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016337:RNA, Catalytic / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D017931:DNA Primers; D007527:Isoenzymes; D019253:Proto-Oncogene Proteins c-bcl-2; D016337:RNA, Catalytic; D051020:bcl-X Protein; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha