Glioma cell sensitivity to topotecan: the role of p53 and topotecan-induced DNA damage.
Topotecan is a topoisomerase I inhibitor which is currently evaluated as an adjuvant agent for malignant glioma. Here, we analysed the effects of topotecan on 12 human malignant glioma cell lines in vitro. All cell lines expressed topoisomerase I mRNA. High p53 protein levels, but not genetic or functional p53 status, were associated with increased topotecan-induced DNA/topoisomerase I complex formation. Neither functional p53 status, nor p53 protein levels, nor complex formation predicted topotecan-induced growth inhibition. We thus confirm a possible role for p53 protein in modulating topoisomerase I activity but conclude that the major molecular determinants of topotecan sensitivity in glioma cells await identification.
Schmidt
F
F
Laboratory of Molecular Neuro-Oncology, Department of Neurology, University of Tübingen, Medical School, Tübingen, Germany.
Rieger
J
J
Wischhusen
J
J
Naumann
U
U
Weller
M
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects* / Q000502:physiology; D004264:DNA Topoisomerases, Type I / Q000187:drug effects* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects*; D016158:Genes, p53 / Q000187:drug effects* / Q000502:physiology; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D019772:Topotecan / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D019772:Topotecan; D004264:DNA Topoisomerases, Type I