Apoptosis is induced in glioma cells by antisense oligonucleotides to protein kinase C alpha and is enhanced by cycloheximide.
The protein kinase C (PKC) activity of human glioma cells correlates with their rate of proliferation. We report here that the down-regulation of the predominant PKC isoform of glioma cells, alpha, by antisense phosphorothioate oligonucleotides (AS PTO) significantly reduced the rate of proliferation of three human glioma cell lines. This reduction in growth rate was attributed to apoptosis, as assessed by terminal deoxynucleotidyl transferase (TdT) assay. Unexpectedly, when low concentrations of the protein synthesis inhibitor cycloheximide (CHX) were administered to A172 cells immediately prior to AS PTO treatment, a marked enhancement in the number of apoptotic cells was observed. These findings suggest that PKC alpha plays a pivotal role in the ability of gliomas to avoid apoptotic cell death.
Dooley
N P
NP
Brain Tumor Research Group, Montreal Neurological Institute, McGill University, Quebec, Canada.
Baltuch
G H
GH
Groome
N
N
Villemure
J G
JG
Yong
V W
VW
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003513:Cycloheximide / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D011500:Protein Synthesis Inhibitors; D003513:Cycloheximide; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha