File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: A novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation

TitleA novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation
Authors
KeywordsAntitumor
Hsp90 inhibitor
Nasopharyngeal carcinoma
Senescence
AT13387
Issue Date2013
Citation
Molecular Cancer, 2013, v. 12, n. 1, article no. 128 How to Cite?
AbstractBackground: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy strongly associated with Epstein-Barr virus (EBV). AT13387 is a novel heat shock protein 90 (Hsp90) inhibitor, which inhibits the chaperone function of Hsp90 and reduces expression of Hsp90-dependent client oncoproteins. This study aimed to evaluate both the in vitro and in vivo antitumor effects of AT13387 in the EBV-positive NPC cell line C666-1.Results: Our results showed that AT13387 inhibited C666-1 cell growth and induced cellular senescence with the downregulation of multiple Hsp90 client oncoproteins EGFR, AKT, CDK4, and restored the protein expression of negative cell cycle regulator p27. We also studied the ability of AT13387 to restore p27 expression by downregulation of AKT and the p27 ubiquitin mediator, Skp2, using AKT inhibitor and Skp2 siRNA. In the functional study, AT13387 inhibited cell migration with downregulation of a cell migration regulator, HDAC6, and increased the acetylation and stabilization of α-tubulin. We also examined the effect of AT13387 on putative cancer stem cells (CSC) by 3-D tumor sphere formation assay. AT13387 effectively reduced both the number and size of C666-1 tumor spheres with decreased expression of NPC CSC-like markers CD44 and SOX2. In the in vivo study, AT13387 significantly suppressed tumor formation in C666-1 NPC xenografts.Conclusion: AT13387 suppressed cell growth, cell migration, tumor sphere formation and induced cellular senescence on EBV-positive NPC cell line C666-1. Also, the antitumor effect of AT13387 was demonstrated in an in vivo model. This study provided experimental evidence for the preclinical value of using AT13387 as an effective antitumor agent in treatment of NPC. © 2013 Chan et al.; licensee BioMed Central Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/214021
ISSN
2015 Impact Factor: 5.888
2015 SCImago Journal Rankings: 2.337
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, King C.-
dc.contributor.authorTing, Choi M.-
dc.contributor.authorChan, Pui S.-
dc.contributor.authorLo, Ming C.-
dc.contributor.authorLo, Kwok W.-
dc.contributor.authorCurry, Jayne E.-
dc.contributor.authorSmyth, Tomoko-
dc.contributor.authorLee, Anne Wing M-
dc.contributor.authorNg, Wai T.-
dc.contributor.authorTsao, George Sai W-
dc.contributor.authorWong, Ricky Ngok S-
dc.contributor.authorLung, Maria L.-
dc.contributor.authorMak, Nai K.-
dc.date.accessioned2015-08-19T13:41:34Z-
dc.date.available2015-08-19T13:41:34Z-
dc.date.issued2013-
dc.identifier.citationMolecular Cancer, 2013, v. 12, n. 1, article no. 128-
dc.identifier.issn1476-4598-
dc.identifier.urihttp://hdl.handle.net/10722/214021-
dc.description.abstractBackground: Nasopharyngeal carcinoma (NPC) is an epithelial malignancy strongly associated with Epstein-Barr virus (EBV). AT13387 is a novel heat shock protein 90 (Hsp90) inhibitor, which inhibits the chaperone function of Hsp90 and reduces expression of Hsp90-dependent client oncoproteins. This study aimed to evaluate both the in vitro and in vivo antitumor effects of AT13387 in the EBV-positive NPC cell line C666-1.Results: Our results showed that AT13387 inhibited C666-1 cell growth and induced cellular senescence with the downregulation of multiple Hsp90 client oncoproteins EGFR, AKT, CDK4, and restored the protein expression of negative cell cycle regulator p27. We also studied the ability of AT13387 to restore p27 expression by downregulation of AKT and the p27 ubiquitin mediator, Skp2, using AKT inhibitor and Skp2 siRNA. In the functional study, AT13387 inhibited cell migration with downregulation of a cell migration regulator, HDAC6, and increased the acetylation and stabilization of α-tubulin. We also examined the effect of AT13387 on putative cancer stem cells (CSC) by 3-D tumor sphere formation assay. AT13387 effectively reduced both the number and size of C666-1 tumor spheres with decreased expression of NPC CSC-like markers CD44 and SOX2. In the in vivo study, AT13387 significantly suppressed tumor formation in C666-1 NPC xenografts.Conclusion: AT13387 suppressed cell growth, cell migration, tumor sphere formation and induced cellular senescence on EBV-positive NPC cell line C666-1. Also, the antitumor effect of AT13387 was demonstrated in an in vivo model. This study provided experimental evidence for the preclinical value of using AT13387 as an effective antitumor agent in treatment of NPC. © 2013 Chan et al.; licensee BioMed Central Ltd.-
dc.languageeng-
dc.relation.ispartofMolecular Cancer-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectAntitumor-
dc.subjectHsp90 inhibitor-
dc.subjectNasopharyngeal carcinoma-
dc.subjectSenescence-
dc.subjectAT13387-
dc.titleA novel Hsp90 inhibitor AT13387 induces senescence in EBV-positive nasopharyngeal carcinoma cells and suppresses tumor formation-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1186/1476-4598-12-128-
dc.identifier.pmid24156782-
dc.identifier.scopuseid_2-s2.0-84886739871-
dc.identifier.hkuros266372-
dc.identifier.volume12-
dc.identifier.issue1-
dc.identifier.spagearticle no. 128-
dc.identifier.epagearticle no. 128-
dc.identifier.eissn1476-4598-
dc.identifier.isiWOS:000329123200001-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats