Carvedilol in glioma treatment alone and with imatinib in vitro

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dc.contributor.authorErguven, Mine
dc.contributor.authorYazihan, Nuray
dc.contributor.authorAktas, Esin
dc.contributor.authorSabanci, Akin
dc.contributor.authorLi, Chiang J.
dc.contributor.authorOktem, Gulperi
dc.contributor.authorBilir, Ayhan
dc.date.accessioned2019-10-27T21:18:21Z
dc.date.available2019-10-27T21:18:21Z
dc.date.issued2010
dc.departmentEge Üniversitesien_US
dc.description.abstractThe purpose of the study was to investigate whether carvedilol has an antiproliferative effect alone and whether carvedilol provides an additive, synergistic or antagonistic effect on imatinib mesylate-induced cytotoxicity in both C6 glioma monolayer and spheroid culture. The C6 rat glioma chemoresistant experimental brain tumour cell line, that is notoriously difficult to treat with combination chemotherapy, was used both in monolayer and spheroid Cultures. We treated C6 glioma cells with carvedilol alone and a combination of carvedilol and imatinib mesylate at a concentration of 10 mu M. Following treatment, we evaluated cell proliferation index. bromodeoxyuridine labelling index (BrDU-LI), cell cycle distributions, apoptotic cell percentages, cAMP levels and three dimensional cell morphology at monolayer cultures. In addition BrDU-LI, volume and morphology of spheroids were also assessed. Carvedilol and imatinib mesylate alone reduced cell number. BrDU-LI cAMP levels and spheroid volume. Carvedilol and imatinib mesylate arrested cells at G0/G1 phase in a time-dependent manner and time-independent manner, respectively. Carvedilol increased apoptosis rate only at the 24th h but imatinib mesylate did for all time intervals. Interestingly carvedilol, drug with well-known protective effect on mitochondria, induced severe mitochondria damage, and imatinib mesylate induced autophagy confirmed only by transmission electron microscopy. These results suggest that carvedilol showed antitumour activity against rat C6 glioma cells and a combination of carvedilol with imatinib mesylate resulted in enhanced in vitro antitumour activity.en_US
dc.description.sponsorshipIstanbul UniversityIstanbul University [484/05052006]; Novartis AG, Basel, Switzerland; Novartis AG, Istanbul, Turkeyen_US
dc.description.sponsorshipThe present work was supported by the Research Fund of Istanbul University, project number 484/05052006. Imatinib was provided by Novartis AG, Basel, Switzerland and Novartis AG, Istanbul, Turkey. The authors thank Fusun Oncu and Ebru Karabulut for their technical assistance. Some parts of this manuscript was presented at the 12th World Congress on Advances in Oncology and and 10th International Symposium On Molecular Medicine, October, 2007, Hersonissos, Crete, Greece.en_US
dc.identifier.doi10.3892/ijo_00000563en_US
dc.identifier.endpage866en_US
dc.identifier.issn1019-6439
dc.identifier.issue4en_US
dc.identifier.pmid20198329en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.startpage857en_US
dc.identifier.urihttps://doi.org/10.3892/ijo_00000563
dc.identifier.urihttps://hdl.handle.net/11454/43967
dc.identifier.volume36en_US
dc.identifier.wosWOS:000275794300014en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpandidos Publ Ltden_US
dc.relation.ispartofInternational Journal of Oncologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectcarvedilolen_US
dc.subjectimatinib mesylateen_US
dc.subjectC6 gliomaen_US
dc.subjectmitochondria damageen_US
dc.subjectautophagyen_US
dc.subjectspheroiden_US
dc.titleCarvedilol in glioma treatment alone and with imatinib in vitroen_US
dc.typeArticleen_US

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