Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia

Cancer Cell. 2011 Nov 15;20(5):674-88. doi: 10.1016/j.ccr.2011.10.015.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Genes, Mitochondrial*
  • Humans
  • Leukemia / drug therapy*
  • Mice
  • Minocycline / analogs & derivatives*
  • Minocycline / pharmacology
  • Mitochondria / drug effects*
  • Mitochondrial Proteins / genetics
  • Neoplastic Stem Cells / drug effects*
  • Peptide Elongation Factor Tu / genetics
  • Protein Biosynthesis / drug effects*
  • RNA, Small Interfering
  • Saccharomyces cerevisiae / drug effects
  • Tigecycline


  • Antineoplastic Agents
  • Mitochondrial Proteins
  • RNA, Small Interfering
  • Tigecycline
  • Peptide Elongation Factor Tu
  • Minocycline