野鸦椿对HeLa细胞的抗增殖作用及其机制的初步研究  

Anti-proliferative Activity and the Mechanisms of Euscaphis Japonica Kanitz in HeLa Cell Line

作　　者：左敏[1] 倪志宇[1] 许立[1] 于峰[1] 吕飒[2] 陈仕萍[2] 广田满[3] 铃木信夫[2] 董玫[1] 

机构地区：[1]河北医科大学法医学系,河北石家庄050017 [2]千叶大学医学部环境影响生物化学教室 [3]信州大学农学部生理活性化学教室

出　　处：《癌变．畸变．突变》2008年第5期350-353,共4页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家教育部归国留学基金(2000479)

摘　　要：背景与目的:从野鸦椿(euscaphis japonica kanitz)枝叶的甲醇提取物分离纯化得到3种酯类化合物7-hydroxy-2-octen-5-olide(1),methyl 5,7-dihydroxy-2(Z)-octenoate(2)和3,7-dihydroxy-5-octanolide(3),对这3种酯类化合物的抗肿瘤细胞增殖作用及其机制进行研究。材料与方法:利用四唑盐(MTT)比色法测定这3种酯类化合物对HeLa细胞增殖的抑制作用;采用流式细胞术检测化合物1对HeLa细胞的凋亡和P53蛋白表达的影响;利用电镜观察化合物1引起HeLa细胞的形态学改变。结果:化合物1和化合物2对体外培养的HeLa细胞的增殖均具有明显地抑制作用,并有较好量效关系,对HeLa细胞增殖的半数抑制浓度分别为49.34μmol/L和24.53μmol/L;流式细胞学检查发现化合物1处理后的HeLa细胞发生凋亡,且P53蛋白表达增加,与对照组比较差异有统计学意义(P<0.01);电镜下可见化合物1引起HeLa细胞凋亡的形态学改变。结论:野鸦椿的提取物7-hydroxy-2-octen-5-olide(1)和methyl 5,7-dihydroxy-2(Z)-octenoate(2)能抑制体外培养的HeLa细胞的增殖,其作用机制可能与调节HeLa细胞P53蛋白表达及诱导HeLa细胞的凋亡有关。BACKGROUND AND AIM: In order to investigate the anti-proliferative activity against HeLa cell line and to explore the possible mechanism of three natural compounds: 7-hydroxy-2-octen-5-olide(1),methyl 5,7-dihydroxy-2(Z)-octenoate(2) and 3,7-dihydroxy-5-octanolide(3) isolated from leaves of Euscaphis japoneca Kantiz.MATERIALS AND METHODS: The anti-proliferative effects of the three compounds on HeLa cells were tested by MTT assay in vitro.The apoptosis induced by above three compounds was studied by FCM.The morphological changes of HeLa cells were examined by transmission electron microscope.RESULTS: Compounds 1 and 2 exhibited dose-dependent anti-proliferative activity on cultured HeLa cells.The concentrations of compounds 1 and 2 resulting in 50% survival rates(IC50) for HeLa cells were 49.34 μmol/L and 24.53 μmol/L,respectively.Comparing with the control group,the apoptosis rate and the expression of P53 in HeLa cells were markedly higher for compound 1 group(P<0.01).The morphological changes of HeLa cells incubated with compound 1 showed chromatin condensation,marginal and nuclear fragmentation.CONCLUSION: 7-Hydroxy-2-octen-5-olide and methyl 5,7-dihydroxy-2(Z)-octenoate isolated from the leaves of Euscaphis japoneca Kanitz could inhibit the proliferation of HeLa cells in vitro.Its anti-prolifrative activity might be associated with upregulating the expression of P53 and inducing the occurrence of apoptosis.

关 键 词：野鸦椿 酯类化合物 抗肿瘤细胞增殖活性 细胞凋亡 P53 

分 类 号：R285.5[医药卫生—中药学]