典型文献
Omeprazole suppresses aggressive cancer growth and metastasis in mice through promoting Snail degradation
文献摘要：
Omeprazole is a proton pump inhibitor that has recently been reported to exhibit anticancer activity against several types of cancer.However,the anticancer mechanisms of omeprazole remain elusive.Snail is an oncogenic zinc finger transcription factor;aberrant activation of Snail is associated with the occurrence and progression of cancer.In this study,we investigated whether Snail acted as a direct anticancer target of omeprazole.We showed that omeprazole displayed a high binding-affinity to recombinant Snail protein(Kd = 0.076 mM),suggesting that omeprazole directly and physically binds to the Snail protein.We further revealed that omeprazole disrupted CREB-binding protein(CBP)/p300-mediated Snail acetylation and then promoted Snail degradation through the ubiquitin-proteasome pathway in HCT116 cells.Omeprazole treatment markedly suppressed Snail-driven epithelial-mesenchymal transition(EMT)in aggressive HCT116,SUM159,and 4T1 cancer cells in vitro and reduced EMT-associated tumor invasion and metastasis in cancer cell xenograft models.Omeprazole also inhibited tumor growth by limiting Snail-dependent cell cycle progression.Overall,this study,for the first time,identifies Snail as a target of omeprazole and reveals a novel mechanism underlying the therapeutic effects of omeprazole against cancer.This study strongly suggests that omeprazole may be an excellent auxiliary drug for treating patients with malignant tumors.
文献关键词：
中图分类号：
作者姓名：
Yang Li;Bo-xue Ren;Hong-mei Li;Tao Lu;Rong Fu;Zhao-qiu Wu
作者机构：
State Key Laboratory of Natural Medicines,School of Biopharmacy,China Pharmaceutical University,Nanjing 211198,China;State Key Laboratory of Natural Medicines,Laboratory of Molecular Design and Drug Discovery,School of Science,China Pharmaceutical University,Nanjing 211198,China
文献出处：
引用格式：
[1]Yang Li;Bo-xue Ren;Hong-mei Li;Tao Lu;Rong Fu;Zhao-qiu Wu-.Omeprazole suppresses aggressive cancer growth and metastasis in mice through promoting Snail degradation)[J].中国药理学报（英文版）,2022(07):1816-1828
A类：
Omeprazole,omeprazole
B类：
suppresses,aggressive,growth,metastasis,mice,through,promoting,Snail,degradation,proton,pump,inhibitor,that,has,recently,been,reported,exhibit,anticancer,activity,against,several,types,However,mechanisms,remain,elusive,oncogenic,zinc,finger,transcription,aberrant,activation,associated,occurrence,progression,In,this,study,investigated,whether,acted,target,We,showed,displayed,high,binding,affinity,recombinant,protein,Kd,mM,suggesting,directly,physically,binds,further,revealed,disrupted,CREB,CBP,p300,mediated,acetylation,then,promoted,ubiquitin,proteasome,pathway,HCT116,cells,treatment,markedly,suppressed,driven,epithelial,mesenchymal,transition,EMT,SUM159,4T1,vitro,reduced,invasion,xenograft,models,also,inhibited,by,limiting,dependent,cycle,Overall,first,identifies,reveals,novel,underlying,therapeutic,effects,This,strongly,suggests,may,excellent,auxiliary,drug,treating,patients,malignant,tumors
AB值：
0.559545
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