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Article: Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib

TitleInduction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib
Authors
Issue Date2016
PublisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html
Citation
Oncotarget, 2016, v. 7 n. 4, p. 4454-4467 How to Cite?
AbstractProteasome inhibitors and histone deacetylase (HDAC) inhibitors can synergistically induce apoptotic cell death in certain cancer cell types but their combinatorial effect on the induction of autophagy remains unknown. Here, we investigated the combinatorial effects of a proteasome inhibitor, bortezomib, and an HDAC inhibitor, romidepsin, on the induction of apoptotic and autophagic cell death in gastric carcinoma (GC) cells. Isobologram analysis showed that low nanomolar concentrations of bortezomib/romidepsin could synergistically induce killing of GC cells. The synergistic killing was due to the summative effect of caspase-dependent intrinsic apoptosis and caspase-independent autophagy. The autophagic cell death was dependent on the activation of MAPK family members (ERK1/2 and JNK), and generation of reactive oxygen species (ROS), but was independent of Epstein-Barr virus infection. In vivo, bortezomib/romidepsin also significantly induced apoptosis and autophagy in GC xenografts in nude mice. This is the first report demonstrating the potent effect of combination of HDAC and proteasome inhibitors on the induction of MAPK- and ROS-dependent autophagy in addition to caspase-dependent apoptosis in a cancer type.
Persistent Identifierhttp://hdl.handle.net/10722/234743
ISSN
2015 Impact Factor: 5.008
2015 SCImago Journal Rankings: 2.294

 

DC FieldValueLanguage
dc.contributor.authorHui, KF-
dc.contributor.authorChiang, AKS-
dc.date.accessioned2016-10-14T13:49:00Z-
dc.date.available2016-10-14T13:49:00Z-
dc.date.issued2016-
dc.identifier.citationOncotarget, 2016, v. 7 n. 4, p. 4454-4467-
dc.identifier.issn1949-2553-
dc.identifier.urihttp://hdl.handle.net/10722/234743-
dc.description.abstractProteasome inhibitors and histone deacetylase (HDAC) inhibitors can synergistically induce apoptotic cell death in certain cancer cell types but their combinatorial effect on the induction of autophagy remains unknown. Here, we investigated the combinatorial effects of a proteasome inhibitor, bortezomib, and an HDAC inhibitor, romidepsin, on the induction of apoptotic and autophagic cell death in gastric carcinoma (GC) cells. Isobologram analysis showed that low nanomolar concentrations of bortezomib/romidepsin could synergistically induce killing of GC cells. The synergistic killing was due to the summative effect of caspase-dependent intrinsic apoptosis and caspase-independent autophagy. The autophagic cell death was dependent on the activation of MAPK family members (ERK1/2 and JNK), and generation of reactive oxygen species (ROS), but was independent of Epstein-Barr virus infection. In vivo, bortezomib/romidepsin also significantly induced apoptosis and autophagy in GC xenografts in nude mice. This is the first report demonstrating the potent effect of combination of HDAC and proteasome inhibitors on the induction of MAPK- and ROS-dependent autophagy in addition to caspase-dependent apoptosis in a cancer type.-
dc.languageeng-
dc.publisherImpact Journals LLC. The Journal's web site is located at http://www.impactjournals.com/oncotarget/index.html-
dc.relation.ispartofOncotarget-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.titleInduction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib-
dc.typeArticle-
dc.identifier.emailHui, KF: kfhui@hku.hk-
dc.identifier.emailChiang, AKS: chiangak@hku.hk-
dc.identifier.authorityChiang, AKS=rp00403-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.18632/oncotarget.6601-
dc.identifier.hkuros269001-
dc.identifier.volume7-
dc.identifier.issue4-
dc.identifier.spage4454-
dc.identifier.epage4467-
dc.publisher.placeUnited States-

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