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"Mechanism for increased sensitivity of acute myeloid leukemia to mitotoxic drugs"

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johan
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Joined: 4 years ago
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https://www.nature.com/articles/s41419-019-1851-3.pdf

"While a cocktail of CCCP and 2-DG inhibited mitochondrial function and depleted ATP in all cell types examined, the effects were much more pronounced for hematological malignancies, when >80% of cancer cells were killed, while approximately three-quarters of normal PBMCs remained viable. We observed that AML-derived cell lines showed higher levels of glycolytic activity than the solid cancer cell lines, like SKOV3. This is probably due to the increased proton leak and mitochondrial uncoupling that were observed in AML-derived cell lines, which limit mitochondrial contribution to cellular energy production"

 

"To the best of our knowledge, the synergistic effect of CCCP and 2-DG in cancer cells has not been reported previously, although 2-DG has been shown to exhibit synergistic effects with metformin, oligomycin, and antimycin44,45. Mitochondrial uncoupling by BCL-2 inhibitors BH3I-2′ and HA14-1 was synergistic with TRAIL-induced apoptosis in leukemia cells46. ABT-199 (venetoclax), a mitocan, and azacitidine (a nucleotide analog) have been proved to be highly active in previously untreated AML patients, eradicating leukemia stem cells20. Also, CPI-613, a novel inhibitor of mitochondrial metabolism via pyruvate dehydrogenase, was effective in patients with refractory AML when combined with cytarabine and mitoxantrone19."


   
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Daniel
(@daniel)
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Nice one Johan! For those who like to have fast access to a list of mitochondria inhibitors, here is a list indicating some accessible ones https://www.cancertreatmentsresearch.com/a-list-of-mitochondria-inhibitors/

 

Kind regards,
daniel


   
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johan
(@j)
Joined: 4 years ago
Posts: 1196
Topic starter  
Posted by: @daniel

Nice one Johan! For those who like to have fast access to a list of mitochondria inhibitors, here is a list indicating some accessible ones https://www.cancertreatmentsresearch.com/a-list-of-mitochondria-inhibitors/

 

Kind regards,
daniel

That is a very comprehensive list! ? 


   
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