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Article: Acridine yellow G blocks glioblastoma growth via dual inhibition of epidermal growth factor receptor and protein kinase C kinases

TitleAcridine yellow G blocks glioblastoma growth via dual inhibition of epidermal growth factor receptor and protein kinase C kinases
Authors
Issue Date2012
Citation
Journal of Biological Chemistry, 2012, v. 287, n. 9, p. 6113-6127 How to Cite?
AbstractAmplification of the epidermal growth factor receptor (EGFR), frequently expressed as a constitutively active deletion mutant (EGFRvIII), occurs commonly in glioblastoma multiformes (GBM). However, blockade of EGFR is therapeutically disappointing for gliomas with PTEN deletion. To search for small molecules treating this aggressive cancer, we have established a cell-based screening and successfully identified acridine yellow G that preferentially blocks cell proliferation of the most malignant U87MG/EGFRvIII cells over the less malignant U87MG/PTEN cells. Oral administration of this compound markedly diminishes the brain tumor volumes in both subcutaneous and intracranial models. It directly inhibits EGFR and PKCs with IC 50 values of ∼7.5 and 5 μM, respectively. It dually inhibits EGFR and PKCs, resulting in a blockade of mammalian target of rapamycin signaling and cell cycle arrest in the G 1phase, which leads to activation of apoptosis in the tumors. Hence, combinatorial inhibition of EGFR and PKCs might provide proof of concept in developing therapeutic agents for treating malignant glioma and other human cancers.
Persistent Identifierhttp://hdl.handle.net/10722/225035
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151

 

DC FieldValueLanguage
dc.contributor.authorQi, Qi-
dc.contributor.authorHe, Kunyan-
dc.contributor.authorYoo, Min Heui-
dc.contributor.authorChan, Chi Bun-
dc.contributor.authorLiu, Xia-
dc.contributor.authorZhang, Zhaobin-
dc.contributor.authorOlson, Jeffrey J.-
dc.contributor.authorXiao, Ge-
dc.contributor.authorWang, Liya-
dc.contributor.authorMao, Hui-
dc.contributor.authorFu, Haian-
dc.contributor.authorTao, Hui-
dc.contributor.authorRamalingam, Suresh S.-
dc.contributor.authorSun, Shi Yong-
dc.contributor.authorMischel, Paul S.-
dc.contributor.authorYe, Keqiang-
dc.date.accessioned2016-04-18T11:16:34Z-
dc.date.available2016-04-18T11:16:34Z-
dc.date.issued2012-
dc.identifier.citationJournal of Biological Chemistry, 2012, v. 287, n. 9, p. 6113-6127-
dc.identifier.issn0021-9258-
dc.identifier.urihttp://hdl.handle.net/10722/225035-
dc.description.abstractAmplification of the epidermal growth factor receptor (EGFR), frequently expressed as a constitutively active deletion mutant (EGFRvIII), occurs commonly in glioblastoma multiformes (GBM). However, blockade of EGFR is therapeutically disappointing for gliomas with PTEN deletion. To search for small molecules treating this aggressive cancer, we have established a cell-based screening and successfully identified acridine yellow G that preferentially blocks cell proliferation of the most malignant U87MG/EGFRvIII cells over the less malignant U87MG/PTEN cells. Oral administration of this compound markedly diminishes the brain tumor volumes in both subcutaneous and intracranial models. It directly inhibits EGFR and PKCs with IC 50 values of ∼7.5 and 5 μM, respectively. It dually inhibits EGFR and PKCs, resulting in a blockade of mammalian target of rapamycin signaling and cell cycle arrest in the G 1phase, which leads to activation of apoptosis in the tumors. Hence, combinatorial inhibition of EGFR and PKCs might provide proof of concept in developing therapeutic agents for treating malignant glioma and other human cancers.-
dc.languageeng-
dc.relation.ispartofJournal of Biological Chemistry-
dc.titleAcridine yellow G blocks glioblastoma growth via dual inhibition of epidermal growth factor receptor and protein kinase C kinases-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1074/jbc.M111.293605-
dc.identifier.pmid22215664-
dc.identifier.scopuseid_2-s2.0-84863119515-
dc.identifier.volume287-
dc.identifier.issue9-
dc.identifier.spage6113-
dc.identifier.epage6127-
dc.identifier.eissn1083-351X-

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