Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide.
Posted by rob on July 27, 2010 under Uncategorized | 
Comments are off for this article
| Related Articles |
Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide.
J Biol Chem. 2010 Jul 23;
Authors: Goussetis DJ, Altman JK, Glaser H, McNeer JL, Tallman MS, Platanias LC
Arsenic trioxide (As2O3) exhibits potent antitumor effects in vitro and in vivo, but the precise mechanisms by which it generates such responses are not well understood. We provide evidence that As2O3 is a potent inducer of autophagy in leukemia cells. Such induction of autophagy by As2O3 appears to require activation of the MEK/ERK pathway, but not the AKT/mTOR or JNK pathways. In efforts to understand the functional relevance of arsenic-induced autophagy, we found that pharmacological inhibitors of autophagy or molecular targeting of beclin 1 or Atg7 result in reversal of the suppressive effects of As2O3 on leukemic cell lines and primary leukemic progenitors from acute myelogenous leukemia (AML) patients. Altogether, our data provide direct evidence that autophagic cell death is critical for the generation of the effects of As2O3 on AML cells and raise the potential of modulating of elements of the autophagic machinery as an approach to enhance the antitumor properties of As2O3 and possibly other heavy metal derivatives.
PMID: 20656687 [PubMed - as supplied by publisher]