典型文献
Benzimidazoles induce concurrent apoptosis and pyroptosis of human glioblastoma cells via arresting cell cycle
文献摘要：
Glioblastoma multiforme(GBM)is the most malignant and lethal primary brain tumor in adults accounting for about 50％of all gliomas.The only treatment available for GBM is the drug temozolomide,which unfortunately has frequent drug resistance issue.By analyzing the hub genes of GBM via weighted gene co-expression network analysis(WGCNA)of the cancer genome atlas(TCGA)dataset,and using the connectivity map(CMAP)platform for drug repurposing,we found that multiple azole compounds had potential anti-GBM activity.When their anti-GBM activity was examined,however,only three benzimidazole compounds,i.e.flubendazole,mebendazole and fenbendazole,potently and dose-dependently inhibited proliferation of U87 and U251 cells with IC50 values below 0.26 μM.Benzimidazoles(0.125-0.5 μM)dose-dependently suppressed DNA synthesis,cell migration and invasion,and regulated the expression of key epithelial-mesenchymal transition(EMT)markers in U87 and U251 cells.Benzimidazoles treatment also dose-dependently induced the GBM cell cycle arrest at the G2/M phase via the P53/P21/cyclin B1 pathway.Furthermore,the drugs triggered pyroptosis of GBM cells through the NF-KB/NLRP3/GSDMD pathway,and might also concurrently induced mitochondria-dependent apoptosis.In a nude mouse U87 cell xenograft model,administration of flubendazole(12.5,25,and 50 mg.kg-1·d-1,i.p,for 3 weeks)dose-dependently suppressed the tumor growth without obvious adverse effects.Taken together,our results demonstrated that benzimidazoles might be promising candidates for the treatment of GBM.
文献关键词：
中图分类号：
作者姓名：
Li-wen Ren;Wan Li;Xiang-jin Zheng;Jin-yi Liu;Yi-hui Yang;Sha Li;Sen Zhang;Wei-qi Fu;Bin Xiao;Jin-hua Wang;Guan-hua Du
作者机构：
The State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100050,China;Key Laboratory of Drug Target Research and Drug Screen,Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College,Beijing 100050,China;Laboratory of Clinical Pharmacy,Ordos School of Clinical Medicine,Inner Mongolia Medical University,Ordos 017099,China
文献出处：
引用格式：
[1]Li-wen Ren;Wan Li;Xiang-jin Zheng;Jin-yi Liu;Yi-hui Yang;Sha Li;Sen Zhang;Wei-qi Fu;Bin Xiao;Jin-hua Wang;Guan-hua Du-.Benzimidazoles induce concurrent apoptosis and pyroptosis of human glioblastoma cells via arresting cell cycle)[J].中国药理学报（英文版）,2022(01):194-208
A类：
Benzimidazoles,azole,flubendazole,mebendazole,fenbendazole,benzimidazoles
B类：
apoptosis,pyroptosis,human,glioblastoma,cells,via,arresting,cycle,Glioblastoma,multiforme,GBM,most,malignant,lethal,primary,brain,tumor,adults,accounting,about,all,gliomas,only,treatment,available,temozolomide,which,unfortunately,frequent,resistance,issue,By,analyzing,hub,genes,weighted,expression,network,analysis,WGCNA,cancer,genome,atlas,TCGA,dataset,using,connectivity,map,CMAP,platform,repurposing,found,that,multiple,compounds,had,potential,anti,activity,When,their,was,examined,however,three,potently,dose,dependently,inhibited,proliferation,U87,U251,IC50,values,below,suppressed,synthesis,migration,invasion,regulated,key,epithelial,mesenchymal,transition,EMT,markers,also,induced,G2,phase,P53,P21,cyclin,B1,pathway,Furthermore,drugs,triggered,through,KB,NLRP3,GSDMD,might,concurrently,mitochondria,In,nude,mouse,xenograft,model,administration,weeks,growth,without,obvious,adverse,effects,Taken,together,our,results,demonstrated,promising,candidates
AB值：
0.570477
相似文献
机标中图分类号，由域田数据科技根据网络公开资料自动分析生成，仅供学习研究参考。
