Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of protein tyrosine kinase and phosphatidylinositol turnover have been found to be associated with cell growth and differentiation. We examined the effects of some inhibitors for these biochemical activities in human myelogenous leukemia cells. Genistein, which is known to inhibit the activities of protein tyrosine kinase, phosphatidylinositol turnover and topoisomerase II, induced nitroblue tetrazolium (NBT) reduction and lysozyme activity in ML-1, HL-60 and U937 cells. Morphological studies showed that genistein-induced differentiation of myeloblastic ML-1 cells into promyelocytes and of promyelocytic HL-60 cells into mature granulocytes. The differentiation-inducing effect of genistein was augmented by addition of 1 alpha,25-dihydroxyvitamin D3 (VD3) or retinoic acid, VD3 being more effective than retinoic acid. Methyl 2,5-dihydroxycinamate, a protein tyrosine kinase inhibitor, had only a weak effect in inducing differentiation of ML-1 cells. On the other hand, psi-tectorigenin was more effective than genistein in inducing the differentiations of ML-1 and HL-60 cells. Psi-tectorigenin is reported to inhibit phosphatidylinositol turnover without inhibiting protein tyrosine kinase. Thus modulation of phosphatidylinositol turnover might be more important than that of protein tyrosine kinase activity for differentiation of some myelogenous leukemia cells.
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PMID:Effects of inhibitors of protein tyrosine kinase activity and/or phosphatidylinositol turnover on differentiation of some human myelomonocytic leukemia cells. 189 51

The effect of genistein, a protein tyrosine kinase and topoisomerase II inhibitor, on the DNA synthesis rate was studied in 21 human glioma specimens obtained at routine craniotomies for tumor resection. Ongoing DNA synthesis rate was determined by using a method based on the generation of tissue mini-units immediately after tumor resection and short incubation time (0-120 min) with [methyl-3H]-thymidine. A 9-77% inhibition of DNA synthesis rate by 100 microM genistein was observed in 18/21 of the glioma specimens. In these cases, the average percentage of inhibition was 55+/-20% (mean+/-SD, P<0.0001, Student's t-test) and the inhibitory effect was >50% in 12/18 of the cases. In 3 cases genistein increased the DNA synthesis rate. The inhibitory effect of genistein had a short-time onset and was concentration-dependent. Additional experiments in 4 cases showed that herbimycin A had no effect on DNA synthesis rate while etoposide inhibited similarly to that of genistein. Our results suggest that the effect of genistein on DNA synthesis rate in gliomas is independent of protein kinase inhibition and probably mediated by topoisomerase II inhibition. In the RG2 model, 50 microM genistein inhibited ongoing DNA synthesis in glioma cells with little or no effect in normal tissue. The data also encourage further investigations on the therapeutic potential of genistein for gliomas.
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PMID:Rapid inhibition of ongoing DNA synthesis in human glioma tissue by genistein. 1963 5