Abstract:
:To identify FDA-approved agents targeting leukemic cells, we performed a chemical screen on two human leukemic cell lines and identified the antimicrobial tigecycline. A genome-wide screen in yeast identified mitochondrial translation inhibition as the mechanism of tigecycline-mediated lethality. Tigecycline selectively killed leukemia stem and progenitor cells compared to their normal counterparts and also showed antileukemic activity in mouse models of human leukemia. ShRNA-mediated knockdown of EF-Tu mitochondrial translation factor in leukemic cells reproduced the antileukemia activity of tigecycline. These effects were derivative of mitochondrial biogenesis that, together with an increased basal oxygen consumption, proved to be enhanced in AML versus normal hematopoietic cells and were also important for their difference in tigecycline sensitivity.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Skrtić M,Sriskanthadevan S,Jhas B,Gebbia M,Wang X,Wang Z,Hurren R,Jitkova Y,Gronda M,Maclean N,Lai CK,Eberhard Y,Bartoszko J,Spagnuolo P,Rutledge AC,Datti A,Ketela T,Moffat J,Robinson BH,Cameron JH,Wrana J,Eavesdoi
10.1016/j.ccr.2011.10.015subject
Has Abstractpub_date
2011-11-15 00:00:00pages
674-88issue
5eissn
1535-6108issn
1878-3686pii
S1535-6108(11)00398-9journal_volume
20pub_type
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