Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide.

The Journal of Biological Chemistry
Dennis J GoussetisLeonidas C Platanias

Abstract

Arsenic trioxide (As(2)O(3)) 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 As(2)O(3) is a potent inducer of autophagy in leukemia cells. Such induction of autophagy by As(2)O(3) appears to require activation of the MEK/ERK pathway but not the AKT/mammalian target of rapamycin 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 results in reversal of the suppressive effects of As(2)O(3) on leukemic cell lines and primary leukemic progenitors from acute myelogenous leukemia patients. Altogether, our data provide direct evidence that autophagic cell death is critical for the generation of the effects of As(2)O(3) on acute myelogenous leukemia cells and raise the potential of modulation of elements of the autophagic machinery as an approach to enhance the antitumor properties of As(2)O(3) and possibly other heavy metal derivatives.

References

May 16, 2002·Seminars in Hematology·Kelly DavisonWilson H Miller
Sep 20, 2002·The Journal of Biological Chemistry·Amit VermaLeonidas C Platanias
Aug 25, 2004·Cell Cycle·Li YuEric H Baehrecke
May 12, 2005·PLoS Biology·William T JacksonKarla Kirkegaard
Sep 9, 2005·Nature Reviews. Cancer·Yasuko KondoSeiji Kondo
Jun 10, 2006·The Journal of Biological Chemistry·Padma Kannan-ThulasiramanLeonidas C Platanias
Jul 29, 2006·Autophagy·Patrick F FinnJ Fred Dice
Sep 28, 2006·Annual Review of Pharmacology and Toxicology·Yoshito Kumagai, Daigo Sumi
Nov 24, 2006·Molecular Cancer Therapeutics·Patrick YoonLeonidas C Platanias
Dec 6, 2006·Cancer Research·David ShackelfordRuibao Ren
Mar 3, 2007·Leukemia·A ErtmerH M Schätzl
Dec 1, 2007·The Journal of Biological Chemistry·Jessica K AltmanLeonidas C Platanias
Jan 5, 2008·British Journal of Haematology·Jianguo WenChung-Che Chang
Feb 27, 2008·The Journal of Biological Chemistry·Blazej DolniakLeonidas C Platanias
May 13, 2008·Nature·Keisuke ItoPier Paolo Pandolfi
Sep 2, 2008·Seminars in Hematology·Martin S Tallman
Jan 28, 2009·Apoptosis : an International Journal on Programmed Cell Death·Avital Eisenberg-Lerner, Adi Kimchi
Feb 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Qun-Ye ZhangZhu Chen
Apr 14, 2009·The Journal of Biological Chemistry·Leonidas C Platanias
May 20, 2009·International Journal of Cancer. Journal International Du Cancer·Anja ApelIngrid Herr
Feb 11, 2010·Cell·Noboru MizushimaBeth Levine

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Citations

Oct 24, 2012·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Alex ZhavoronkovAlexey Moskalev
Sep 1, 2011·Molecular Cancer Therapeutics·Zhineng J YangFrank A Sinicrope
Dec 2, 2011·PloS One·Fernanda Caroline CarvalhoMaria-Cristina Roque-Barreira
Aug 3, 2012·Chinese Journal of Cancer·Su-Ping ZhangJian-Rong Wang
Jul 26, 2012·International Journal of Cell Biology·Versha Banerji, Spencer B Gibson
Apr 4, 2014·Experimental Cell Research·Nina OrfaliNigel P Mongan
Sep 14, 2011·Evidence-based Complementary and Alternative Medicine : ECAM·Min Ho HanYung Hyun Choi
Jul 14, 2011·Leukemia & Lymphoma·Ganchimeg IshdorjSpencer B Gibson
Jan 15, 2015·International Journal of Molecular Sciences·Amr AminRegine Schneider-Stock
Mar 19, 2013·Biochemical and Biophysical Research Communications·Sung Youl KimJeen-Woo Park
Jul 10, 2012·American Journal of Otolaryngology·Rong KangShu-Xin Wen
Feb 22, 2012·Current Opinion in Chemical Biology·Jian-Xiang LiuZhu Chen
May 27, 2011·Critical Reviews in Oncology/hematology·Huseyin Atakan EkizYusuf Baran
Apr 23, 2011·Cancer Letters·Guangmin XiHuiqing Yuan
Oct 7, 2014·Biochimica Et Biophysica Acta·Cecilia EvangelistiAlberto M Martelli
Aug 23, 2011·International Journal of Cancer. Journal International Du Cancer·Satoshi ShimizuNorio Hayashi
Dec 20, 2011·Biochimica Et Biophysica Acta·Seoung Woo ShinJeen-Woo Park
Feb 5, 2013·Cancer Biology & Therapy·John P GalvinLeonidas C Platanias
Feb 6, 2014·Cancer Biology & Therapy·Edward J WuLeonidas C Platanias
Dec 3, 2014·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Victoria CavaliereGuillermo A Blanco
May 2, 2014·European Journal of Pharmacology·Sina KardehAli Mohammad Alizadeh
Oct 14, 2014·Chemical Research in Toxicology·Sarmishtha ChatterjeeShelley Bhattacharya
Jan 1, 2012·Cells·Roberto Chiarelli, Maria Carmela Roccheri
Jan 1, 2011·Cancers·Niamh H MolloyAdrienne M Gorman
Feb 2, 2019·Cells·Mojgan Djavaheri-MergnyMagali Humbert
Jan 1, 2012·Asian Pacific Journal of Cancer Prevention : APJCP·Guo-Xuan LuoYong Zhang
Aug 12, 2018·Scientific Reports·Marzieh Zeinvand-LorestaniSoheila Alboghobeish

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