Abstract:
BACKGROUND: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.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Bredholt T,Dimba EA,Hagland HR,Wergeland L,Skavland J,Fossan KO,Tronstad KJ,Johannessen AC,Vintermyr OK,Gjertsen BTdoi
10.1186/1476-4598-8-101subject
Has Abstractpub_date
2009-11-13 00:00:00pages
101issn
1476-4598pii
1476-4598-8-101journal_volume
8pub_type
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