2种苯并呋喃衍生物对肝癌细胞的毒性及活性氧机制  

Cytotoxicity and Reactive Oxygen Species Related Mechanism on HepG2 Cells of Two Benzofuran Derivatives

作　　者：赵晶[1] 蒲丽平[1] 杨精涛[1] 刘权[2] 高清祥[1] 王勤[1] 王春明[1] 

机构地区：[1]兰州大学生命科学学院生物物理研究所,兰州730000 [2]兰州大学功能有机分子化学国家重点实验室,兰州730000

出　　处：《中国实验方剂学杂志》2010年第16期105-108,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：省部共建新疆特种植物药资源教育部重点实验室开放课题(ZWY200806)

摘　　要：目的:比较离舌橐吾Ligularia veitchiana(Hemsl.)Greenm的2种苯并呋喃衍生物5,6-二甲氧基-2-异丙基-苯并呋喃(5,6-dimethoxy-2-isopropenyl-benzofuran,化合物1),5-乙酰基-6-甲氧基-2-异丙基-苯并呋喃(5-acetyl-6-methoxy-2-isopropenyl-benzofuran,化合物2)对人肝癌细胞HepG2和正常肝细胞L02的毒性,并分析其可能机制。方法:用台盼蓝排染法检测化合物细胞毒性、用DCFH-DA荧光分光光度计法检测细胞活性氧含量、用钼酸铵比色法检测过氧化氢酶活性。结果:化合物1和2对L02的IC50分别为(171.2±3.3)mg·L-1和(79.0±4.1)mg·L-1,高于对HepG2的IC50(84.2±6.5)mg.L-1和(65.2±1.9)mg·L-1,表明肿瘤细胞比正常细胞对化合物更加敏感。用化合物1和2 IC50处理细胞48 h,测得HepG2细胞活性氧分别是对照组的1.6倍和3.2倍;L02细胞活性氧分别是对照组的1.2倍和1.8倍。化合物1和2处理后,HepG2细胞过氧化氢酶活力分别从对照组的(17.2±1.7)U·mg-1下降到(12.8±0.4)和(6.4±0.1)U·mg-1;L02细胞过氧化氢酶活力分别从对照组的(17.7±1.2)U·mg-1下降到(14.3±1.5)和(8.6±0.5)U·mg-1;HepG2过氧化氢酶活力降低幅度大于L02。结论:2个化合物对HepG2的毒性和活性氧的增幅均大于L02,同时HepG2过氧化氢酶活力降幅也大于L02。据此推测2个化合物细胞毒性与活性氧有关。Objective：This study was to evaluate the effect of two benzofuran derivatives on human liver hepatocellular carcinoma cells HepG2 and human hepatic L02 cells in vitro.Method：5,6-dimethoxy-2-isopropenyl-benzofuran（compound 1） and 5-acetyl-6-methoxy-2-isopropenyl-benzofuran（compound 2） were isolated from Ligularia veitchiana（Hemsl.） Greenm.Trypan blue exclusion staining,2′,7′-dichlorofluorescin diacetate（DCFHDA） fluorescence spectrophotometry,and ammonium molybdate colorimetric assay were used to evaluate cytotoxicity,reactive oxygen species（ROS） generation,and catalase activity respectively.Result：The results showed that IC50 of compound 1 and 2 on L02 cells are（171.2±3.3）mg·L^-1 and（79.0±4.1）mg·L^-1,higher than that on HepG2,（84.2±6.5）mg·L^-1 and（65.2±1.9）mg·L^-1,exhibited more potent cytotoxic effect on tumor cells.After treated with the half inhibitory concentration（IC50） of compound 1 and 2 for 48 hours,ROS generated in HepG2 cells were 1.6 and 3.2 folds to the control group,and 1.2 and 1.8 folds in L02 cells respectively.Higher ROS generations in HepG2 cells than L02 were found.The catalase activity decreased from the control group（17.2± 1.7） U.mg·L^-1 to（12.8 ± 0.4） and（6.4 ± 0.1） U.mg·L^-1 after treated with compound 1 and 2 in HepG2 cell respectively,and decreased from the control group（17.7±1.2）U·mg·L^-1 to（14.3±1.5）and（8.6±0.5）U·mg·L^-1 in L02 cells.Higher catalase activity reduced in HepG2 cells than L02.Conclusion：According to the more potent cytotoxicity,the ROS generation increasing in HepG2 than L02,and the decreasing of catalase activity in HepG2 cells,we suppose that the mechanism of the cytotoxicity for these two benzofuran deravatives may relate to ROS theory.

关 键 词：离舌橐吾 苯并呋喃 细胞毒 活性氧 

分 类 号：R285.5[医药卫生—中药学]