ETOPOSIDE SENSITIVITY OF RADIORESISTANT HUMAN GLIOMA CELL-LINES

Purpose: Malignant gliomas display aggressive local behavior and are n ot cured by existing therapy. Etoposide, a topoisomerase-II-inhibitor agent, is one of the most active and useful antineoplastic agents. How ever, etoposide is not usually used on these tumors. We undertook an i n vitro study to prove that etoposide is a useful drug for malignant g liomas. 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 mu g/ml (range 8-15.8 mu g/ml). Since topoisomerase II is the critical target for eto poside, 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. Re sults: The topoisomerase II activity was homogeneous in glioma cell li nes (average of 50% decatenation with 7,000 cells), and topoisomerase II was the target of the etoposide. Conclusions: Our results suggest t hat topoiomerase II-reactive agents may prove to be clinically useful drugs for patients with malignant gliomas.