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Protein kinase C inhibitors suppress cell growth in established and low-passage
glioma cell lines.
A comparison between staurosporine and tamoxifen
Baltuch GH, Couldwell WT, Villemure JG, Yong VW
Department of Neurology and Neurosurgery, Montreal Neurological
Institute, McGill University, Quebec, Canada.
We have previously demonstrated that the proliferation of established human
glioma cell lines correlated with protein kinase C (PKC) activity and that a
relatively selective PKC inhibitor, staurosporine, inhibits glioma cell
proliferation.
The purpose of this study was to determine whether low-passage
glioma cell lines were also sensitive to staurosporine and to compare the
antimitotic effects of staurosporine with tamoxifen, an antiestrogen with a
known PKC inhibitory effect presently being investigated in the treatment of
recurrent glioma.
We measured the effects of treatment with staurosporine or
tamoxifen on the proliferation rate of five established glioma cell lines (A172,
U251, U87, U373, U563) and four low-passage glioma cell lines.
The proliferation
of all cell lines was inhibited by staurosporine, at an IC50 value
(concentration at which activity is 50% inhibited) of approximately 2 nmol/L.
All established lines, but only one low-passage line, were susceptible to
tamoxifen, with an IC50 value of 10 mumol/L.
Three of the four low-passage lines
were poorly inhibited by tamoxifen.
The IC50 values for the inhibition of
cellular proliferation by staurosporine and tamoxifen closely corresponds to the
IC50 data for the inhibition of particulate PKC activity in gliomas.
We conclude
that staurosporine is more effective in the inhibition of glioma proliferation
than tamoxifen and that staurosporine is potentially useful in the adjuvant
treatment of gliomas.
The correspondence in IC50 results for proliferation and
PKC activity further strengthens the hypothesis that an aberrant PKC system in
gliomas drives their hyperproliferative state.
PMID: 8413883 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8413883
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