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

作　　者：叶玉梅[1] 徐承熊[1] 

机构地区：[1]中国医学科学院中国协和医科大学药物研究所

出　　处：《中国药理学与毒理学杂志》1997年第3期211-214,共4页Chinese Journal of Pharmacology and Toxicology

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．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.

关 键 词：肿瘤 海南粗榧新碱 衍生物 DNA 拓扑异构酶 

分 类 号：R979.1[医药卫生—药品]