Recent studies have suggested that the
triphenylethylene antiestrogen tamoxifen inhibits the proliferation in vitro of a substantial percentage of cell lines derived from adult high-grade
gliomas, potentially acting through inhibition of the second messenger
protein kinase C. These findings have formed the impetus for clinical trials of this agent in adults with
malignant gliomas. However, it has previously remained uncertain whether
tamoxifen has a similar inhibitory effect on the proliferation of pediatric high-grade
gliomas, and whether low-grade
gliomas, which constitute the majority of glial
neoplasms in children, are also inhibited by this agent. To address these issues, the present study examined the effect of
tamoxifen on proliferation and viability in a series of low-passage cell lines derived both from low-grade and high-grade pediatric
gliomas. This agent was tested in three
malignant gliomas, two
pilocytic astrocytomas, two non-pilocytic low-grade
astrocytomas, 1
mixed glioma, and 1
oligodendroglioma.
Tamoxifen produced a dose-dependent inhibition of proliferation in two of the three
malignant glioma cell lines and in each of the low-grade
glioma cell lines with a 50% effective dose of approximately 3 micrograms/ml (5.4 microM), which is comparable to the IC50 for inhibition of PKC activity by this agent. No significant cytotoxicity was encountered at this concentration. However, complete elimination of proliferation was achieved with a dose of 10 micrograms/ml (17.8 microM), which produced a direct cytotoxic effect. We conclude that
tamoxifen inhibits proliferation of cell lines derived from both low-grade and high-grade pediatric glial
tumors in vitro at concentrations that may be achievable clinically with high-dose oral
therapy.(ABSTRACT TRUNCATED AT 250 WORDS)