Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis

dc.contributor.authorGhoochani, Ali
dc.contributor.authorMajernik, Gökce Hatipoglu
dc.contributor.authorSehm, Tina
dc.contributor.authorWach, Sven
dc.contributor.authorBuchfelder, Michael
dc.contributor.authorTaubert, Helge
dc.contributor.authorEyupoglu, Ilker Y.
dc.contributor.authorSavaskan, Nicolai
dc.date.accessioned2017-10-09
dc.date.available2017-09-27
dc.date.created2016
dc.date.issued2017-10-09
dc.description.abstractTaxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. Cabazitaxel (XRP-6258, Jevtana®) is a second generation semisynthetic taxane with high chemotherapeutic potential in prostate cancer. There, cabazitaxel can overcome docetaxel-resistant prostate cancer. Here, we tested the effects of cabazitaxel on glioma cells, and non-transformed cells such as neurons and astrocytes. Cabazitaxel operates highly toxic in various human glioma cells at nanomolar concentrations. In contrast, primary astrocytes and neurons are not affected by this agent. Cabazitaxel disrupts cytoskeletal F-actin fibers and induces apoptotic cell death in gliomas. Moreover, cabazitaxel displayed highest efficacy in inhibiting glioma cell migration and invasion. Here we demonstrate that cabazitaxel inhibited tumor migration already at 1 nM. We also tested cabazitaxel in the ex vivo VOGiM assay. Cabazitaxel stalled glioma growth and at the same time inhibited tumor-induced angiogenesis. In summary, we found that cabazitaxel operates as an apoptosis-inducing gliomatoxic agent with strongest effects on migration and invasive growth. Thus, our report uncovered cabazitaxel actions on gliomas and on the brain tumor microenvironment. These data reveal novel aspects for adjuvant approaches when applied to brain tumor patients.en
dc.format.extent38306-38318
dc.identifier.citationOncotarget 7.25 (2016): S. 38306-38318. <http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=9439&path[]=30950>
dc.identifier.doihttps://doi.org/10.18632/oncotarget.9439
dc.identifier.opus-id8794
dc.identifier.urihttps://open.fau.de/handle/openfau/8794
dc.identifier.urnurn:nbn:de:bvb:29-opus4-87942
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/de/deed.de
dc.subjectgliomas
dc.subjectneurotoxicity
dc.subjecttaxane
dc.subjectangiogenesis
dc.subjectcell death
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleCabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesisen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.issue25
local.journal.titleOncotarget
local.journal.volume7
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.gnd-
local.subject.sammlungUniversität Erlangen-Nürnberg / Von der FAU geförderte Open Access Artikel / Von der FAU geförderte Open Access Artikel 2016
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