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dc.contributor.authorBredholt, Thereseen_US
dc.contributor.authorDimba, Elizabeth A. O.en_US
dc.contributor.authorHagland, Hanneen_US
dc.contributor.authorWergeland, Lineen_US
dc.contributor.authorSkavland, Jørnen_US
dc.contributor.authorFossan, Kjell Oveen_US
dc.contributor.authorTronstad, Karl Johanen_US
dc.contributor.authorJohannessen, Anne Christineen_US
dc.contributor.authorVintermyr, Olav Karstenen_US
dc.contributor.authorGjertsen, Bjørn Toreen_US
dc.date.accessioned2010-09-14T12:49:15Z
dc.date.available2010-09-14T12:49:15Z
dc.date.issued2009-11-13eng
dc.PublishedMolecular Cancer 8(101)en
dc.identifier.issn1476-4598
dc.identifier.urihttps://hdl.handle.net/1956/4182
dc.description.abstractBackground: An organic extract of the recreational herb khat (Catha edulis Forsk.) triggers cell death in various leukemia cell lines in vitro. The chemotherapeutics camptothecin, a plant alkaloid topoisomerase I inhibitor, was tested side-by-side with khat in a panel of acute myeloid leukemia cell lines to elucidate mechanisms of toxicity. Results: Khat had a profound effect on MOLM-13 cells inducing mitochondrial damage, chromatin margination and morphological features of autophagy. The effects of khat on mitochondrial ultrastructure in MOLM-13 correlated with strongly impaired routine respiration, an effect neither found in the khat-resistant MV-4-11 cells nor in camptothecin treated cells. Enforced expression of anti-apoptotic Bcl-2 protein provided protection against camptothecin-induced cell death and partly against khat toxicity. Khat-induced cell death in MOLM-13 cells included reduced levels of anti-apoptotic Mcl-1 protein, while both khat and camptothecin induced c-FLIPL cleavage and procaspase-8 activation. Conclusion: Khat activated a distinct cell death pathway in sensitive leukemic cells as compared to camptothecin, involving mitochondrial damage and morphological features of autophagy. This suggests that khat should be further explored in the search for novel experimental therapeutics.en_US
dc.language.isoengeng
dc.publisherBioMed Centraleng
dc.rightsAttribution CC BYeng
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/eng
dc.titleCamptothecin and khat (Catha edulis Forsk.) induced distinct cell death phenotypes involving modulation of c-FLIPL, Mcl-1, procaspase-8 and mitochondrial function in acute myeloid leukemia cell linesen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2009 Bredholt et al; licensee BioMed Central
dc.rights.holderBredholt et al; licensee BioMed Central
dc.identifier.doihttps://doi.org/10.1186/1476-4598-8-101
dc.subject.nsiVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Hematologi: 775nob


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