二烯丙基二硫通过活性氧介导的JNK信号通路诱导人白血病K562细胞凋亡  

Diallyl disulfide induces apoptosis of human leukemia K562 cells through activation of JNK mediated by reactive oxygen

作　　者：易岚[1,2] 谭晖[1] 吉晓霞[1] 陈歆[1] 单健[1] 苏琦[1] 

机构地区：[1]南华大学肿瘤研究所,湖南衡阳421001 [2]南华大学药学与生命科学学院,湖南衡阳421001

出　　处：《中国药理学通报》2013年第4期473-477,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81100375);南华大学博士启动基金资助项目(No 2011XQD60)

摘　　要：目的研究二烯丙基二硫(DADS)诱导人白血病K562细胞凋亡的分子机制。方法应用MTT法检测细胞的活性;用流式细胞术检测细胞凋亡以及细胞内的活性氧(reac-tive oxygen species,ROS)水平;Western blot检测JNK以及磷酸化JNK的活化。结果 DADS能明显抑制K562细胞的增殖,呈时间和剂量依赖性;5.0 mg.L-1DADS处理K562细胞,细胞内ROS水平在1 h后明显增加,8 h达到高峰,随后又开始下降。随着DADS剂量的增加,JNK的活性明显增强,在DADS处理K562细胞8 h后,磷酸化的JNK达到最高值,而在随后的4 h又明显降低。Sp600125和NAC能明显减少磷酸化JNK的表达和抑制DADS诱导的细胞凋亡。结论 ROS是DADS诱导K562细胞凋亡过程中JNK活化的有效调节剂,DADS通过ROS介导的JNK活化诱导人白血病K562细胞凋亡。Aim To research the molecular mechanisms of DADS-induced apoptosis of human leukemia K562 cells.Methods Cell viability was measured by MTT;cell apoptosis was tested by flow cytometer;Levels of DADS-induced ROS were measured by 2′,7′-dichlorofluorescein diacetate（DCFH-DA） fluorescence;DADS-induced phosphorylated JNK levels were measured by western blot.Results The DADS-treated K562 cells showed a dose-and time-dependent decrease in cell viability and proliferation.Levels of DADS-induced ROS also showed time-dependent increases in K562 cells.K562 cells exposed to 5.0 mg·L-1 DADS for 8 h showed maximum levels of phosphorylated JNK,which decreased when exposed for additional 4 hours.In contrast,Sp600125,a specific inhibitor of JNK,blocked apoptosis of K562 cells exposed to DADS.N-acetylcysteine（NAC）,a known antioxidant,also decreased ROS generation,effectively blocked apoptosis,and decreased DADS-induced phosphorylated JNK levels.Conclusion JNK is involved in DADS-induced ROS-mediated apoptosis of K562 cells.

关 键 词：DADS JNK 活性氧 凋亡 K562 细胞 

分 类 号：R284.1[医药卫生—中药学] R329.25[医药卫生—中医学]