| (+)α-Tocopheryl succinate inhibits the mitochondrial respiratory chain complex I and is as effective as arsenic trioxide or ATRA against acute promyelocytic leukemia in vivo. | |
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MedLine Citation:
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PMID: 21869839 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The vitamin E derivative (+)α-tocopheryl succinate (α-TOS) exerts pro-apoptotic effects in a wide range of tumors and is well tolerated by normal tissues. Previous studies point to a mitochondrial involvement in the action mechanism; however, the early steps have not been fully elucidated. In a model of acute promyelocytic leukemia (APL) derived from hCG-PML-RARα transgenic mice, we demonstrated that α-TOS is as effective as arsenic trioxide or all-trans retinoic acid, the current gold standards of therapy. We also demonstrated that α-TOS induces an early dissipation of the mitochondrial membrane potential in APL cells and studies with isolated mitochondria revealed that this action may result from the inhibition of mitochondrial respiratory chain complex I. Moreover, α-TOS promoted accumulation of reactive oxygen species hours before mitochondrial cytochrome c release and caspases activation. Therefore, an in vivo antileukemic action and a novel mitochondrial target were revealed for α-TOS, as well as mitochondrial respiratory complex I was highlighted as potential target for anticancer therapy.Leukemia advance online publication, 26 August 2011; doi:10.1038/leu.2011.216. |
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Authors:
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G A S Dos Santos; R S Abreu E Lima; C R Pestana; A S G Lima; P S Scheucher; C H Thomé; H L Gimenes-Teixeira; B A A Santana-Lemos; A R Lucena-Araujo; F P Rodrigues; R Nasr; S A Uyemura; R P Falcão; H de Thé; P P Pandolfi; C Curti; E M Rego |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-26 |
Journal Detail:
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Title: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K Volume: - ISSN: 1476-5551 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8704895 Medline TA: Leukemia Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Hematology Division, Department of Internal Medicine, National Institute of Science and Technology on Cell Based Therapy, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil [2] Department of Physics and Chemistry, Pharmaceutical Sciences Faculty of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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