Inhibition of topoisomerase II alpha subunit de novo synthesis by specific antisense oligonucleotides suppresses human glioma T98G cell growth.
Deoxyribonucleic acid (DNA) topoisomerases are enzymes which resolve topological problems in eukaryotic DNA, and may be involved in cell proliferation. The involvement of topoisomerase II in cell proliferation was examined in the human glioma cell line T98G. The growth rate of T98G cells was suppressed by treatment with topoisomerase II antisense oligonucleotides dose-dependently, with significant suppression at concentrations greater than of 0.1 mM. The growth rate of T98G treated with control oligonucleotide was suppressed at concentrations greater than 3.0 mM. The activity of topoisomerase II in T98G cells treated with 0.5 mM topoisomerase II antisense oligonucleotide was one fourth of that in cells treated with control oligonucleotide. When topoisomerase II translation was suppressed, the activity of topoisomerase I was increased. These results suggest that de novo synthesis of the topoisomerase II protein is required to maintain a normal growth rate in cultured T98G cells. These topoisomerases may be functionally related, and might provide compensatory mechanisms in the case of compromised function.
Shin
M
M
Department of Neurological Surgery, Faculty of Medicine, Kagawa Medical University, Japan.
Kimura
S
S
Nagao
S
S
D000951:Antigens, Neoplasm; D002455:Cell Division / Q000187:drug effects; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D016376:Oligonucleotides, Antisense; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II