Antitumor activity of a novel bis-aziridinylnaphthoquinone (AZ4) mediating cell cycle arrest and apo

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:lalalan
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
Aim:The cytotoxic activities of a series of bis-aziridinylnaphthoquinone,AZ1 toAZ4,on human lung carcinoma cell lines,H460,and normal lung cells fibroblastcell line,MRC-5,and the mechanisms of H460 cells induced by AZ4 wereinvestigated.Methods:The MTT assay was used to determine the cellproliferation.Cell cycle was analysed by FACS.The activity of caspase 3,8 and 9was determined by cell-permeable fluorogenic detection system.Western blotassay was used to evaluate the regulation of cyclin B,Cdc-2,p53,p21,and the Bcl-2 protein.Results:AZ1 to AZ4 displayed various cytotoxicity activities againstH460 and MRC-5 cells.Compared to those compounds,AZ4 was with the mosteffective agent among the 5 tested analogues at reducing H460 cell viability with anIC_(50) value of 1.23 μmol/L;it also exhibited weak cytotoxicity against MRC-5 cells withan IC_(50) value of 12.7 μmol/L.The results show that growth arrest on the G_2-M phaseof H460 cells induced by AZ4 for 24 h was discovered,and this might be alteredwith the reduced Cdc-2 protein expression of 47% at 2.0 μmol/L AZ4,but not withcyclin B protein expression.The AZ4 treated cells were then led to apoptosis after48 h.This was associated with the activation of apoptotic enzyme caspase 3 andmediated by caspase 8,but not caspase 9 at various concentrations of AZ4 afterbeing cultured for 48 h and 30 h,respectively.The anti-apoptotic protein (Bcl-2)expression in H460 cells altered by 39% with downregulation,and the p53 proteinby 25% with upregulation after being cultured with 2.0 μmol/L AZ4 for 48 h.In atime-dependent wanrer,the expression of the p53 and p21 proteins were increasedto the maximum at 24 h,and then decreased at 48.Conclusion:AZ4 represents anovel antitumor aziridinylnaphthoquinone with therapeutic potential against thenon-small cell lung cancer cells. Aim: The cytotoxic activities of a series of bis-aziridinylnaphthoquinone, AZ1 to AZ4, on human lung carcinoma cell lines, H460, and normal lung cells fibroblast cell line, MRC-5, and the mechanisms of H460 cells induced by AZ4 were investigated. The MTT assay was used to determine the cell proliferation assay. Cell cycle was analyzed by FACS. The activity of caspase 3, 8 and 9 was determined by cell-permeable fluorogenic detection system. Western blot assay was used to evaluate the regulation of cyclin B, Cdc-2, p53, p21, and the Bcl-2 protein. Results: AZ1 to AZ4 displayed various cytotoxicity activities against H460 and MRC-5 cells. Compared to these compounds, AZ4 was with the mosteffective agent among the five tested analogues at reducing H460 cell viability with an IC_ (50) value of 1.23 μmol / L; it also showed weak cytotoxicity against MRC-5 cells withan IC 50 value of 12.7 μmol / L.The results show that growth arrest on the G_2-M phase of H460 cells induced by AZ4 for 24 h was discovered, and this might be alteredwith the reduced Cdc-2 protein expression of 47% at 2.0 μmol / L AZ4, but not with cyclin B protein expression. The AZ4 treated cells were then led to apoptosis after 48 h. This was associated with the activation of apoptotic enzyme caspase 3 and mediated by caspase 8, but not caspase 9 at various concentrations of AZ4 after beating cultured for 48 h and 30 h, respectively. The anti-apoptotic protein (Bcl-2) expression in H460 cells altered by 39% with downregulation, and the p53 protein by 25% with upregulation after being cultured with 2.0 μmol / L AZ4 for 48 h. In a time-dependent wanrer, the expression of the p53 and p21 proteins were increased to the maximum at 24 h, and then decreased at 48. Conlusion: AZ4 represents an ovel antitumor aziridinylnaphthoquinone with therapeutic potential against thenon-small cell lung cancer cells.
其他文献
一张白纸,平平无奇,然而,古往今来,一些名人在上面用尽心思、做足文章,不仅展现了超群的智慧,也留下了动人的美谈。赵匡胤一张白纸的圣旨公元960年,宋太祖赵匡胤派曹彬为主帅
初中语文课堂提问学生响应不积极,提问效果不佳,学生对于课堂提问不支持,不配合是语文教育需要面对的一个现实问题.而怎样通过合理的教学措施提高语文课堂提问的质量,让学生
“绿色汽车”离我们还有多远?──’96北京国际电动汽车及代用燃料汽车技术交流、研讨会暨展览会侧记本刊记者李新生1展会、技术交流、研讨会概况《’96北京国际电动汽车及代用燃料
目的优选纤维素酶法提取响铃草总黄酮的最佳工艺。方法采用分光光度法,先分别考察乙醇体积分数、酶质量浓度、pH、提取温度、液料比、提取时间对响铃草总黄酮提取率的影响,然
老年性白内障是致盲原因之一,但摘除后可重见光明。为探讨术后远期(随访时)疗效,我们随访105只眼施行囊内和囊外术后的病人,同时对术后近期(出院时)视力均进行了统计分析,今
本文叙述了北京市汽车制动泵厂在为切诺基国产化方面所做的技术改造及近年生产经营情况。 This article describes the Beijing Automobile Brake Pump Factory in Cherokee
6月,应俄罗斯公共关系协会邀请,中国国际公共关系协会代理会长赵大力赴莫斯科开展行业交流,分别会见了俄罗斯公共关系协会会长纳乌莫夫、俄乌拉尔地区公共关系协会会长格拉齐
在社会经济高速发展的今天,公路车辆的日益增多,这就对我们现今的公路要求高了很多,所以在这样的一个现实状况下,如果要能继续保证所有运行在上面的汽车能够高速、安全的行驶
本文介绍了采用初始磁导率法和扫频共振法对轻型发动机曲轴及凸轮轴铸造质量进行综合检测的原理和方法。 This paper introduces the principles and methods of comprehens
本文旨在研究中耳压力变化对外耳的影响。作者选择28例年龄5~48岁、无其他全身性疾患的复发性外耳炎患者,清洁外耳道作排出物培养和敏感试验、测量鼓室压,并对有中耳负压的病