| Literature DB >> 22094260 |
Marko Skrtić1, Shrivani Sriskanthadevan, Bozhena Jhas, Marinella Gebbia, Xiaoming Wang, Zezhou Wang, Rose Hurren, Yulia Jitkova, Marcela Gronda, Neil Maclean, Courteney K Lai, Yanina Eberhard, Justyna Bartoszko, Paul Spagnuolo, Angela C Rutledge, Alessandro Datti, Troy Ketela, Jason Moffat, Brian H Robinson, Jessie H Cameron, Jeffery Wrana, Connie J Eaves, Mark D Minden, Jean C Y Wang, John E Dick, Keith Humphries, Corey Nislow, Guri Giaever, Aaron D Schimmer.
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. 2011 Elsevier Inc. All rights reserved.Entities:
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Year: 2011 PMID： 22094260 PMCID： PMC3221282 DOI： 10.1016/j.ccr.2011.10.015
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743