Difference between revisions of "Bredholt T 2009 Mol Cancer"
| (10 intermediate revisions by 4 users not shown) | |||
| Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=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. | |title=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. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/19912650 PMID: 19912650] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/19912650 PMID: 19912650 Open Access] | ||
|authors=Bredholt T, Dimba EA, Hagland HR, Wergeland L, Skavland J, Fossan KO, Tronstad KJ, Johannessen AC, Vintermyr OK, Gjertsen BT | |authors=Bredholt T, Dimba EA, Hagland HR, Wergeland L, Skavland J, Fossan KO, Tronstad KJ, Johannessen AC, Vintermyr OK, Gjertsen BT | ||
|year=2009 | |year=2009 | ||
|journal=Mol Cancer | |journal=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. | |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. | 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. | ||
| Line 11: | Line 11: | ||
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. | 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. | ||
|keywords=Mitochondria, Oxidative phosphorilation, Programmed cell death, Camptothecin | |keywords=Mitochondria, Oxidative phosphorilation, Programmed cell death, Camptothecin | ||
|mipnetlab=NO Bergen Tronstad KJ | |mipnetlab=NO Bergen Tronstad KJ | ||
|discipline=Mitochondrial Physiology, Environmental Physiology; Toxicology, Pharmacology; Biotechnology | |discipline=Mitochondrial Physiology, Environmental Physiology; Toxicology, Pharmacology; Biotechnology | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Genetic knockout;overexpression, Pharmacology;toxicology | |||
|diseases=Cancer | |||
|injuries=Cell death | |||
|organism=Human | |||
|tissues=Blood cells | |||
|preparations=Intact cells | |||
|enzymes=Complex II;succinate dehydrogenase | |||
|topics=ADP, Inhibitor | |||
|couplingstates=ROUTINE | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
| | |additional=Leukemia, | ||
|discipline=Mitochondrial Physiology, Environmental Physiology; Toxicology, Pharmacology; Biotechnology | |discipline=Mitochondrial Physiology, Environmental Physiology; Toxicology, Pharmacology; Biotechnology | ||
}} | }} | ||
Latest revision as of 18:19, 31 January 2020
| 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. |
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. • Keywords: Mitochondria, Oxidative phosphorilation, Programmed cell death, Camptothecin
• 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
