If. Pollack et S. Kawecki, THE EFFICACY OF TAMOXIFEN AS AN ANTIPROLIFERATIVE AGENT IN-VITRO FOR BENIGN AND MALIGNANT PEDIATRIC GLIAL TUMORS, Pediatric neurosurgery, 22(6), 1995, pp. 281-288
Recent studies have suggested that the triphenylethylene antiestrogen
tamoxifen inhibits the proliferation in vitro of a substantial percent
age of cell lines derived from adult high-grade gliomas, potentially a
cting through inhibition of the second messenger protein kinase C. The
se 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 pro
liferation of pediatric high-grade gliomas, and whether low-grade glio
mas, which constitute the majority of glial neoplasms in children, are
also inhibited by this agent. To address these issues, the present st
udy examined the effect of tamoxifen on proliferation and viability in
a series of low-passage cell lines derived both from low-grade and hi
gh-grade pediatric gliomas. This agent was tested in three malignant g
liomas, two pilocytic astrocytomas, two non-pilocytic low-grade astroc
ytomas, 1 mixed glioma, and 1 oligodendroglioma. Tamoxifen produced a
dose-dependent inhibition of proliferation in two of the three maligna
nt glioma cell lines and in each of the low-grade glioma cell lines wi
th a 50% effective dose of approximately 3 mu g/ml (5.4 mu M), which i
s comparable to the IC50 for inhibition of PKC activity by this agent.
No significant cytotoxicity was encountered at this concentration. Ho
wever, complete elimination of proliferation was achieved with a dose
of 10 mu g/ml(17.8 mu M), 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 t
herapy. Accordingly, clinical trials using this agent have been initia
ted for children with high-grade glial tumors that have progressed aft
er standard therapy to determine the safety and efficacy of tamoxifen
for these patients.