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海南粗榧新碱衍生物HH07A对肿瘤细胞内DNA拓扑异构酶Ⅱ和蛋白激酶C活性的影响
Effect of hainanensine derivative HH07A on activities of DNA topoisomerase Ⅱ and protein kinase C in tumor cells
【摘要】 HH07A5.5μmolL-1作用L1210细胞24h后,可使细胞的DNA拓扑异构酶Ⅱ活性下降;在无细胞系统,HH07A0.55mmolL-1也能直接促进DNA拓扑异构酶Ⅱ引起的DNA链断裂.经HH07A(L1210细胞5.5μmolL-1,HL-60细胞8.25μmolL-1)作用24h后,L1210及HL-60细胞的胞浆蛋白激酶C(PKC)活性升高,胞膜PKC活性下降,而全细胞PKC活性变化不大.在无细胞系统中,HH07A1.1mmolL-1能明显抑制PKC的活性.
【Abstract】 The activity of DNA topoisomerase Ⅱ was determined with PBR322 DNA as the substrate. The experimental results showed that the activity of the enzyme of L1210 cells was decreased after the cells were exposed to HH07A {1 (3′ methyl butyl) 14,15 methylene dioxy 3, 4, 5, 6, 7, 9, 10 heptahydro cyclopentano(j,k) pyrrolo benzoazepine} 5.5 μmol·L 1 for 24 h, and high concentration of HH07A (0.55 mmol·L 1 ) can directly stimulate the DNA cleavage induced by DNA topoisomerase Ⅱ, but HH07A itself did not induce PBR322 DNA cleavage. These results suggest that the cleavage of DNA induced by HH07A may be mediated by its effect on the activity of DNA topoisomerase Ⅱ. The activities of the protein kinase C (PKC) of L1210 cells and HL 60 cells were measured. After the cells were incubated with HH07A for 24 h, the decrease in cell membrane PKC activity was accompanied by an increase in cytosolic PKC activity, but the whole cellular PKC activity was not changed obviously. The results suggest that HH07A may influence the distribution of cellular PKC in L1210 cells and HL 60 cells. In the cell free system, HH07A also inhibited the activity of PKC in dose dependent way.
【Key words】 antineoplastic agents; HH07A; cell line,L1210; cell line,HL 60; DNA topoisomerase Ⅱ; protein kinases;
- 【文献出处】 中国药理学与毒理学杂志 ,CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY , 编辑部邮箱 ,1997年03期
- 【分类号】R979.1
- 【被引频次】4
- 【下载频次】74