title: t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activating NF-κB-p65.
abstract: Although sEH inhibitors are well studied in inflammatory and cardiovascular diseases, their effects on gliomas are unclear. In this study, we investigated the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87 human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell line. Our results showed that t-AUCB efficiently inhibited sEH activities in all three cell lines (the inhibition rate was more than 80% in each) and suppressed U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth inhibition on HepG2. We detected high levels of phosphorylated NF-κB-p65 (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-κB inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-κB-p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation level. We propose to further test this promising reagent for its anti-glioma activity in clinical relevant orthotopic brain glioma models.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, Jiangsu, China.
authors.forename: Junyang
authors.initials: J
authors.lastname: Li
authors.forename: Hongyi
authors.initials: H
authors.lastname: Liu
authors.forename: Biao
authors.initials: B
authors.lastname: Xing
authors.forename: Yanzhe
authors.initials: Y
authors.lastname: Yu
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Gu
authors.forename: Guofeng
authors.initials: G
authors.lastname: Zhang
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Gu
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Weixing
authors.initials: W
authors.lastname: Hu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C524106:4-(4-(3-adamantan-1-ylureido)cyclohexyloxy)benzoic acid; D001565:Benzoates; C530104:CCND1 protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D019938:Cyclin D1; D014508:Urea; D004851:Epoxide Hydrolases