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  4. The Aurora kinase inhibitor VE-465 has anticancer effects in pre-clinical studies of human hepatocellular carcinoma
 
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The Aurora kinase inhibitor VE-465 has anticancer effects in pre-clinical studies of human hepatocellular carcinoma

Journal
Journal of Hepatology
Journal Volume
50
Journal Issue
3
Pages
518-527
Date Issued
2009
Author(s)
ZHONG-ZHE LIN  
Hsu H.-C.
CHIH-HUNG HSU  
Yeh P.-Y.
Huang C.-Y.F.
Huang Y.-F.
Chen T.-J.
SUNG-HSIN KUO  
CHIUN HSU  
Hu F.-C.
YUNG-MING JENG  
Chung Y.
ANN-LII CHENG  
DOI
10.1016/j.jhep.2008.10.022
URI
https://www.scopus.com/inward/record.uri?eid=2-s2.0-59349096086&doi=10.1016%2fj.jhep.2008.10.022&partnerID=40&md5=61d7ac8ef71d579d8fef36b84e4a278d
https://scholars.lib.ntu.edu.tw/handle/123456789/473421
Abstract
Background/Aims: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and novel therapies are urgently needed. Recently, aberrant expression of Aurora kinases has been reported in various human cancers including HCC. We sought to investigate the potential of a potent and selective Aurora kinase inhibitor, VE-465, for targeted therapy of HCC. Methods: Cytotoxicity effects of VE-465 were tested in Huh-7 and HepG2 cell lines. Inhibition of Aurora kinase activity was demonstrated by Western blotting and immunofluorescence staining. Mitotic perturbation was visualized by confocal microscopy. Cell cycle profiles and apoptosis were assessed by flow cytometry. In vivo efficacy was determined in nude mice with human HCC xenografts. Results: We demonstrated that VE-465 induced proliferation blockade, histone H3 (Ser10) dephosphorylation, mitotic disturbance, endoreduplication, and apoptosis in Huh-7 and HepG2 cells. We also found that VE-465 suppressed Aurora kinase activity, prevented tumor growth, and induced apoptosis in a Huh-7 xenograft model. Conclusions: These findings show that VE-465 has potent anticancer effects in human HCC. Inhibitors of Aurora kinases may deserve further exploration as molecular targeted agents against HCC. ? 2008 European Association for the Study of the Liver.
SDGs

[SDGs]SDG3

Other Subjects
aurora kinase inhibitor; cyclopropanecarboxylic acid [4 [4 (4 methyl 1 piperazinyl) 6 (5 methyl 2h pyrazol 3 ylamino) 2 pyrimidinylthio]phenyl]amide; histone H3; protein serine threonine kinase; unclassified drug; ve 465; animal experiment; animal model; antineoplastic activity; apoptosis; article; cancer inhibition; cell cycle; cell proliferation; cell strain HepG2; confocal microscopy; controlled study; cytotoxicity; drug efficacy; drug screening; drug structure; endoreduplication; enzyme activity; enzyme inhibition; enzyme repression; flow cytometry; human; human cell; immunofluorescence test; in vivo study; liver cell carcinoma; mitosis; mouse; nonhuman; nude mouse; priority journal; protein dephosphorylation; Western blotting; xenograft; Antineoplastic Agents; Apoptosis; Carcinoma, Hepatocellular; Cell Division; Cell Line, Tumor; Cell Survival; Histones; Humans; Liver Neoplasms; Mitosis; Piperazines; Protein-Serine-Threonine Kinases
Type
journal article

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