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Clozapine, a neuroleptic agent, inhibits Akt by counteracting Ca2+/calmodulin in PTEN-negative U-87MG human glioblastoma cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Shin, Soon Young | - |
dc.contributor.author | Choi, Byeong Hyeok | - |
dc.contributor.author | Ko, Jesang | - |
dc.contributor.author | Kim, Se Hyun | - |
dc.contributor.author | Kim, Yong Sik | - |
dc.contributor.author | Lee, Young Han | - |
dc.date.accessioned | 2009-12-23T05:09:11Z | - |
dc.date.available | 2009-12-23T05:09:11Z | - |
dc.date.issued | 2006-03-18 | - |
dc.identifier.citation | Cell Signal. 2006 Nov;18(11):1876-86. Epub 2006 Mar 6. | en |
dc.identifier.issn | 0898-6568 (Print) | - |
dc.identifier.uri | http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T2M-4JDN6F4-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=596260bb3181c322ff2d35b249c5fd5f | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16542821 | - |
dc.identifier.uri | https://hdl.handle.net/10371/22107 | - |
dc.description.abstract | Clozapine (CZP), a dibenzodiazepine derivative with a piperazinyl side chain, is in clinical use as an antipsychotic drug. This study investigated the effect of CZP on the modulation of the PI3K/Akt/GSK-3beta pathway in PTEN-negative U-87MG glioblastoma cells. Treatment with CZP rapidly inhibited the basal and EGF-induced phosphorylation of Akt. The inhibition of Akt resulted in the dephosphorylation of GSK-3beta and increased GSK-3beta kinase activity. A voltage-sensitive Ca(2+) channel blocker and calmodulin (CaM) antagonists inhibited Akt phosphorylation, whereas elevation of the intracellular Ca(2+) concentration prevented CZP-induced dephosphorylation of Akt and GSK-3beta, suggesting that Ca(2+)/CaM participates in the inhibition of Akt by CZP in U-87MG cells. In addition, similar to LY294002, CZP arrested cell cycle progression at G0/G1 phase, which was accompanied by decreased expression of cyclin D1. The reduction in the cyclin D1 level induced by CZP was abrogated by the inhibition of GSK-3beta, the inhibition of proteasome-dependent proteolysis, or an increase in the intracellular Ca(2+) concentration. These results suggest that the antipsychotic drug CZP modulates the PI3K/Akt/GSK-3beta pathway by counteracting Ca(2+)/CaM in PTEN-negative U-87MG glioblastoma cells. | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | Antipsychotic Agents/pharmacology | en |
dc.subject | Calcium/*metabolism | en |
dc.subject | Calmodulin/*metabolism | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Clozapine/*pharmacology | en |
dc.subject | Cytoskeletal Proteins/metabolism | en |
dc.subject | Gene Deletion | en |
dc.subject | Glioblastoma/drug therapy/genetics/*metabolism | en |
dc.subject | Humans | en |
dc.subject | Nuclear Proteins/metabolism | en |
dc.subject | PTEN Phosphohydrolase/genetics | en |
dc.subject | Phosphorylation | en |
dc.subject | Proto-Oncogene Proteins c-akt/*antagonists & inhibitors | en |
dc.subject | Signal Transduction | en |
dc.subject | Tumor Cells, Cultured | en |
dc.title | Clozapine, a neuroleptic agent, inhibits Akt by counteracting Ca2+/calmodulin in PTEN-negative U-87MG human glioblastoma cells | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 신순영 | - |
dc.contributor.AlternativeAuthor | 최병혁 | - |
dc.contributor.AlternativeAuthor | 고제상 | - |
dc.contributor.AlternativeAuthor | 김세현 | - |
dc.contributor.AlternativeAuthor | 김용식 | - |
dc.contributor.AlternativeAuthor | 이영한 | - |
dc.identifier.doi | 10.1016/j.cellsig.2006.02.004 | - |
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