Etoposide sensitivity of radioresistant human glioma cell lines.
OBJECTIVE
Malignant gliomas display aggressive local behavior and are not cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. However, etoposide is not usually used on these tumors. We undertook an in vitro study to prove that etoposide is a useful drug for malignant gliomas.


METHODS
Five human glioma cell lines were the basis for this study. Following exposure to various concentrations of etoposide, the glioma cell lines were found to be sensitive; the median concentration inhibiting the number of cells by 50% (IC50) was 8.76 microg/ml (range 8-15.8 microg/ml). Since topoisomerase II is the critical target for etoposide, it was of interest to determine the topoisomerase II activity (decatenation of kinetoplast DNA isolated from Cryphtidia fasciculata) and the etoposide-induced inhibition of topoisomerase II activity.


RESULTS
The topoisomerase II activity was homogeneous in glioma cell lines (average of 50% decatenation with 7,000 cells), and topoisomerase II was the target of the etoposide.


CONCLUSIONS
Our results suggest that topoiomerase II-reactive agents may prove to be clinically useful drugs for patients with malignant gliomas.
Beauchesne
P
P
Department of Radiation Oncology, Mayo Clinic Center, Rochester, Minnesota, USA.
Bertrand
S
S
N'guyen
M J
MJ
Christianson
T
T
Dore
J F
JF
Mornex
F
F
Bonner
J A
JA
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D004250:DNA Topoisomerases, Type II