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dc.contributor.authorProchazka, Lubomir
dc.contributor.authorTuranek, Jaroslav
dc.contributor.authorTesarik, Radek
dc.contributor.authorKnotigova, Pavlina
dc.contributor.authorPolaskova, Pavlina
dc.contributor.authorAndrysik, Zdenek
dc.contributor.authorKozubik, Alois
dc.contributor.authorZak, Frantisek
dc.contributor.authorSova, Petr
dc.contributor.authorNeuzil, Jiri
dc.contributor.authorMachala, Miroslav
dc.date.accessioned2017-05-03T12:46:25Z
dc.date.available2017-05-03T12:46:25Z
dc.date.issued2007
dc.date.modified2009-09-09T07:17:42Z
dc.identifier.issn0003-9861
dc.identifier.doi10.1016/j.abb.2007.03.021
dc.identifier.urihttp://hdl.handle.net/10072/18792
dc.description.abstractA new hydrophobic platinum(IV) complex, LA-12, a very efficient anticancer drug lacking cross-resistance with cisplatin (CDDP), is now being tested in clinical trials. Here we investigated the apoptogenic activity of LA-12 and its effect on gap-junctional intercellular communication (GJIC) in the rat liver epithelial cell line WB-F344. LA-12 induced apoptosis much more efficiently than did CDDP due to a combination of rapid penetration into the cell and attack on DNA, leading to fast activation of p53 and caspase-3. Exposure of WB-F344 cells to LA-12 led to rapid induction of the time- and dose-dependent decrease in GJIC. On the molecular level, loss of GJIC induced by LA-12 was mediated by activation of extracellular signal-regulated kinase (ERK)-1 and ERK-2, as demonstrated by the use of inhibitors of ERK activation. Inhibition of GJIC was linked to rapid hyperphosphorylation of connexin-43 and disappearance of connexon clusters from membranes, which was not observed in the case of CDDP.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.publisher.placeThe Netherlands
dc.publisher.urihttp://www.elsevier.com/wps/find/journaldescription.cws_home/622787/description#description
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom54
dc.relation.ispartofpageto61
dc.relation.ispartofissue1
dc.relation.ispartofjournalArchives of Biochemistry and Biophysics
dc.relation.ispartofvolume462
dc.rights.retentionY
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchcode3101
dc.titleApoptosis and inhibition of gap-junctional intercellular communication induced by LA-12, a novel hydrophobic platinum(IV) complex
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.rights.copyright© 2007 Elsevier. Please refer to the journal's website for access to the definitive, published version.
gro.date.issued2007
gro.hasfulltextNo Full Text
gro.griffith.authorNeuzil, Jiri


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