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Bredholt T 2009 Mol Cancer

From Bioblast
Publications in the MiPMap
Bredholt T, Dimba EA, Hagland HR, Wergeland L, Skavland J, Fossan KO, Tronstad KJ, Johannessen AC, Vintermyr OK, Gjertsen BT (2009) Camptothecin 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 lines. Mol Cancer 8:101.

Β» PMID: 19912650 Open Access

Bredholt T, Dimba EA, Hagland HR, Wergeland L, Skavland J, Fossan KO, Tronstad KJ, Johannessen AC, Vintermyr OK, Gjertsen BT (2009) Mol Cancer

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. β€’ Keywords: Mitochondria, Oxidative phosphorilation, Programmed cell death, Camptothecin

β€’ O2k-Network Lab: NO Bergen Tronstad KJ


Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology  Pathology: Cancer  Stress:Cell death  Organism: Human  Tissue;cell: Blood cells  Preparation: Intact cells  Enzyme: Complex II;succinate dehydrogenase  Regulation: ADP, Inhibitor  Coupling state: ROUTINE 

HRR: Oxygraph-2k 

Leukemia