Published in Cancer Detection and Prevention 1996; 20(5).

Role of a topo II - inhibitor drug, etoposide, in the treatment of malignant gliomas: an experimental study

P Beauchesne MD, J Bonner MD, C Soler MD, F Mornex MD

AIM: Etoposide, a Topo II-inhibitor drug, is currently being explored as a therapeutic agent for malignant gliomas which are not always cured by radiochemotherapy associations. The study compared the in vitro etoposide sensitivity of human glioma cells VS human squamous cell carcinoma (SCC) cells. METHODS: A panel of 12 human cell lines (6 high-grade glioma cell lines and 6 head and neck SCC cell lines) were studied. A standard colony formation assay was used to assess cell survival. Since Topoisomerase II is the critical target for etoposide, Topoisomerase II content (immunoprecipitation), Topoisomerase II activity (decatenation of kDNA isolated from crithidia fasciculata) and etoposide-induced inhibition of Topoisomerase II activity for the glioma cells is the SCC cells were determined. RESULTS: Following exposure to various concentrations of etoposide, the glioma cells were found to have a similar median and range of IC 50 values compared to the SCC cells: - Gliomas: 11.2 ug/ml, 8-16 ug/ml; - SCC: 11.6 ug/ml, 2.5-24 ug/ml. The Topoisomerase II content was higher but not significant in SCC cells than glioma cells. Topoisomerase II activity was the same for both cell lines; the average of number of cells to obtain 50% of decatenation were respectively for gliomas and SCC carcinomas 7000 and 8000 cells. No difference was found in two cells lines for etoposide-induced inhibition of Topoisomerase II activity. CONCLUSIONS: These results suggest that the Topoisomerase II - reactive agents may prove to be clinically useful agents for patients with high grade gliomas.

KEY WORDS: gliomas, etoposide, Topoisomerase II, chemotherapy.

Paper presented at the International Symposium on the Impact of Cancer Biotechnology on Diagnostic and Prognostic Indicators; Nice, France; October 26 - 28, 1996; in the section on Chemotherapy.

http://www.cancerprev.org/Journal/Issues/20/5/505/1555