RapamycinFungusV1, Main, Exploration, bibRecord, 000E67

Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells.

Identifieur interne : 000E67 ( Main/Exploration ); précédent : 000E66; suivant : 000E68

Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells.

Auteurs : Biljana Ristic [Serbie] ; Mihajlo Bosnjak [Serbie] ; Katarina Arsikin [Serbie] ; Aleksandar Mircic [Serbie] ; Violeta Suzin-Zivkovic [Serbie] ; Andrija Bogdanovic [Serbie] ; Vladimir Perovic [Serbie] ; Tamara Martinovic [Serbie] ; Tamara Kravic-Stevovic [Serbie] ; Vladimir Bumbasirevic [Serbie] ; Vladimir Trajkovic [Serbie] ; Ljubica Harhaji-Trajkovic [Serbie]

Source :

Experimental cell research [ 1090-2422 ] ; 2014.

RBID : pubmed:24907655

Descripteurs français

English descriptors

Abstract

We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy.

DOI: 10.1016/j.yexcr.2014.05.021
PubMed: 24907655

Affiliations:

Serbie

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<author><name sortKey="Kravic Stevovic, Tamara" sort="Kravic Stevovic, Tamara" uniqKey="Kravic Stevovic T" first="Tamara" last="Kravic-Stevovic">Tamara Kravic-Stevovic</name>
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<author><name sortKey="Mircic, Aleksandar" sort="Mircic, Aleksandar" uniqKey="Mircic A" first="Aleksandar" last="Mircic">Aleksandar Mircic</name>
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<author><name sortKey="Bogdanovic, Andrija" sort="Bogdanovic, Andrija" uniqKey="Bogdanovic A" first="Andrija" last="Bogdanovic">Andrija Bogdanovic</name>
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<author><name sortKey="Perovic, Vladimir" sort="Perovic, Vladimir" uniqKey="Perovic V" first="Vladimir" last="Perovic">Vladimir Perovic</name>
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<author><name sortKey="Martinovic, Tamara" sort="Martinovic, Tamara" uniqKey="Martinovic T" first="Tamara" last="Martinovic">Tamara Martinovic</name>
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<country xml:lang="fr">Serbie</country>
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<author><name sortKey="Kravic Stevovic, Tamara" sort="Kravic Stevovic, Tamara" uniqKey="Kravic Stevovic T" first="Tamara" last="Kravic-Stevovic">Tamara Kravic-Stevovic</name>
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<country xml:lang="fr">Serbie</country>
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<author><name sortKey="Bumbasirevic, Vladimir" sort="Bumbasirevic, Vladimir" uniqKey="Bumbasirevic V" first="Vladimir" last="Bumbasirevic">Vladimir Bumbasirevic</name>
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<country xml:lang="fr">Serbie</country>
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<author><name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name>
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<country xml:lang="fr">Serbie</country>
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<author><name sortKey="Harhaji Trajkovic, Ljubica" sort="Harhaji Trajkovic, Ljubica" uniqKey="Harhaji Trajkovic L" first="Ljubica" last="Harhaji-Trajkovic">Ljubica Harhaji-Trajkovic</name>
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<idno type="eISSN">1090-2422</idno>
<imprint><date when="2014" type="published">2014</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult (MeSH)</term>
<term>Antibiotics, Antineoplastic (pharmacology)</term>
<term>Apoptosis (drug effects)</term>
<term>Apoptosis Regulatory Proteins (metabolism)</term>
<term>Autophagy (drug effects)</term>
<term>Beclin-1 (MeSH)</term>
<term>Cell Proliferation (drug effects)</term>
<term>Humans (MeSH)</term>
<term>Idarubicin (pharmacology)</term>
<term>Immunoenzyme Techniques (MeSH)</term>
<term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (drug therapy)</term>
<term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (metabolism)</term>
<term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive (pathology)</term>
<term>Lymphocytes (cytology)</term>
<term>Lymphocytes (drug effects)</term>
<term>Lymphocytes (metabolism)</term>
<term>Membrane Potential, Mitochondrial (drug effects)</term>
<term>Membrane Proteins (metabolism)</term>
<term>Microscopy, Electron, Scanning (MeSH)</term>
<term>Microscopy, Fluorescence (MeSH)</term>
<term>Phosphorylation (drug effects)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (metabolism)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology)</term>
<term>Proto-Oncogene Proteins c-akt (metabolism)</term>
<term>Signal Transduction (drug effects)</term>
<term>TOR Serine-Threonine Kinases (metabolism)</term>
<term>Tumor Cells, Cultured (MeSH)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte (MeSH)</term>
<term>Antibiotiques antinéoplasiques (pharmacologie)</term>
<term>Apoptose (effets des médicaments et des substances chimiques)</term>
<term>Autophagie (effets des médicaments et des substances chimiques)</term>
<term>Bécline-1 (MeSH)</term>
<term>Cellules cancéreuses en culture (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Idarubicine (pharmacologie)</term>
<term>Leucémie myéloïde chronique BCR-ABL positive (anatomopathologie)</term>
<term>Leucémie myéloïde chronique BCR-ABL positive (métabolisme)</term>
<term>Leucémie myéloïde chronique BCR-ABL positive (traitement médicamenteux)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (anatomopathologie)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (métabolisme)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (traitement médicamenteux)</term>
<term>Lymphocytes (cytologie)</term>
<term>Lymphocytes (effets des médicaments et des substances chimiques)</term>
<term>Lymphocytes (métabolisme)</term>
<term>Microscopie de fluorescence (MeSH)</term>
<term>Microscopie électronique à balayage (MeSH)</term>
<term>Phosphorylation (effets des médicaments et des substances chimiques)</term>
<term>Potentiel de membrane mitochondriale (effets des médicaments et des substances chimiques)</term>
<term>Prolifération cellulaire (effets des médicaments et des substances chimiques)</term>
<term>Protéines membranaires (métabolisme)</term>
<term>Protéines proto-oncogènes c-akt (métabolisme)</term>
<term>Protéines régulatrices de l'apoptose (métabolisme)</term>
<term>Sérine-thréonine kinases TOR (métabolisme)</term>
<term>Techniques immunoenzymatiques (MeSH)</term>
<term>Transduction du signal (effets des médicaments et des substances chimiques)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Apoptosis Regulatory Proteins</term>
<term>Membrane Proteins</term>
<term>Proto-Oncogene Proteins c-akt</term>
<term>TOR Serine-Threonine Kinases</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Antibiotics, Antineoplastic</term>
<term>Idarubicin</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Leucémie myéloïde chronique BCR-ABL positive</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
</keywords>
<keywords scheme="MESH" qualifier="cytologie" xml:lang="fr"><term>Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="cytology" xml:lang="en"><term>Lymphocytes</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term>
<term>Autophagy</term>
<term>Cell Proliferation</term>
<term>Lymphocytes</term>
<term>Membrane Potential, Mitochondrial</term>
<term>Phosphorylation</term>
<term>Signal Transduction</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Apoptose</term>
<term>Autophagie</term>
<term>Lymphocytes</term>
<term>Phosphorylation</term>
<term>Potentiel de membrane mitochondriale</term>
<term>Prolifération cellulaire</term>
<term>Transduction du signal</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</term>
<term>Lymphocytes</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Leucémie myéloïde chronique BCR-ABL positive</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
<term>Lymphocytes</term>
<term>Protéines membranaires</term>
<term>Protéines proto-oncogènes c-akt</term>
<term>Protéines régulatrices de l'apoptose</term>
<term>Sérine-thréonine kinases TOR</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Leukemia, Myelogenous, Chronic, BCR-ABL Positive</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Antibiotiques antinéoplasiques</term>
<term>Idarubicine</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Leucémie myéloïde chronique BCR-ABL positive</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Beclin-1</term>
<term>Humans</term>
<term>Immunoenzyme Techniques</term>
<term>Microscopy, Electron, Scanning</term>
<term>Microscopy, Fluorescence</term>
<term>Tumor Cells, Cultured</term>
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<term>Bécline-1</term>
<term>Cellules cancéreuses en culture</term>
<term>Humains</term>
<term>Microscopie de fluorescence</term>
<term>Microscopie électronique à balayage</term>
<term>Techniques immunoenzymatiques</term>
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<front><div type="abstract" xml:lang="en">We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy. </div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24907655</PMID>
<DateCompleted><Year>2014</Year>
<Month>09</Month>
<Day>23</Day>
</DateCompleted>
<DateRevised><Year>2016</Year>
<Month>11</Month>
<Day>25</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1090-2422</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>326</Volume>
<Issue>1</Issue>
<PubDate><Year>2014</Year>
<Month>Aug</Month>
<Day>01</Day>
</PubDate>
</JournalIssue>
<Title>Experimental cell research</Title>
<ISOAbbreviation>Exp Cell Res</ISOAbbreviation>
</Journal>
<ArticleTitle>Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells.</ArticleTitle>
<Pagination><MedlinePgn>90-102</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.yexcr.2014.05.021</ELocationID>
<ELocationID EIdType="pii" ValidYN="Y">S0014-4827(14)00229-8</ELocationID>
<Abstract><AbstractText>We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy. </AbstractText>
<CopyrightInformation>Copyright © 2014 Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ristic</LastName>
<ForeName>Biljana</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bosnjak</LastName>
<ForeName>Mihajlo</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Arsikin</LastName>
<ForeName>Katarina</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mircic</LastName>
<ForeName>Aleksandar</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Suzin-Zivkovic</LastName>
<ForeName>Violeta</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bogdanovic</LastName>
<ForeName>Andrija</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Clinic for Hematology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Perovic</LastName>
<ForeName>Vladimir</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Martinovic</LastName>
<ForeName>Tamara</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Kravic-Stevovic</LastName>
<ForeName>Tamara</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bumbasirevic</LastName>
<ForeName>Vladimir</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade, Serbia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Trajkovic</LastName>
<ForeName>Vladimir</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade, Serbia. Electronic address: vtrajkovic@med.bg.ac.rs.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Harhaji-Trajkovic</LastName>
<ForeName>Ljubica</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Institute for Biological Research, University of Belgrade, Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade, Serbia. Electronic address: buajk@yahoo.com.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2014</Year>
<Month>06</Month>
<Day>05</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>Exp Cell Res</MedlineTA>
<NlmUniqueID>0373226</NlmUniqueID>
<ISSNLinking>0014-4827</ISSNLinking>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000903">Antibiotics, Antineoplastic</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D051017">Apoptosis Regulatory Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="C491997">BECN1 protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000071186">Beclin-1</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D008565">Membrane Proteins</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="C546842">MTOR protein, human</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.1.1</RegistryNumber>
<NameOfSubstance UI="D058570">TOR Serine-Threonine Kinases</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber>
<NameOfSubstance UI="D051057">Proto-Oncogene Proteins c-akt</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>ZRP63D75JW</RegistryNumber>
<NameOfSubstance UI="D015255">Idarubicin</NameOfSubstance>
</Chemical>
</ChemicalList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000903" MajorTopicYN="N">Antibiotics, Antineoplastic</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
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<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051017" MajorTopicYN="N">Apoptosis Regulatory Proteins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D001343" MajorTopicYN="N">Autophagy</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000071186" MajorTopicYN="N">Beclin-1</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D049109" MajorTopicYN="N">Cell Proliferation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015255" MajorTopicYN="N">Idarubicin</DescriptorName>
<QualifierName UI="Q000494" MajorTopicYN="Y">pharmacology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007124" MajorTopicYN="N">Immunoenzyme Techniques</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015464" MajorTopicYN="N">Leukemia, Myelogenous, Chronic, BCR-ABL Positive</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008214" MajorTopicYN="N">Lymphocytes</DescriptorName>
<QualifierName UI="Q000166" MajorTopicYN="N">cytology</QualifierName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D053078" MajorTopicYN="N">Membrane Potential, Mitochondrial</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008565" MajorTopicYN="N">Membrane Proteins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008855" MajorTopicYN="N">Microscopy, Electron, Scanning</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008856" MajorTopicYN="N">Microscopy, Fluorescence</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D054198" MajorTopicYN="N">Precursor Cell Lymphoblastic Leukemia-Lymphoma</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="N">drug therapy</QualifierName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D051057" MajorTopicYN="N">Proto-Oncogene Proteins c-akt</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015398" MajorTopicYN="N">Signal Transduction</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058570" MajorTopicYN="N">TOR Serine-Threonine Kinases</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014407" MajorTopicYN="N">Tumor Cells, Cultured</DescriptorName>
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<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Apoptosis</Keyword>
<Keyword MajorTopicYN="N">Autophagy</Keyword>
<Keyword MajorTopicYN="N">Idarubicin</Keyword>
<Keyword MajorTopicYN="N">Leukemia</Keyword>
<Keyword MajorTopicYN="N">mTOR</Keyword>
</KeywordList>
</MedlineCitation>
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<Month>03</Month>
<Day>07</Day>
</PubMedPubDate>
<PubMedPubDate PubStatus="revised"><Year>2014</Year>
<Month>05</Month>
<Day>21</Day>
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<PubMedPubDate PubStatus="accepted"><Year>2014</Year>
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<tree><country name="Serbie"><noRegion><name sortKey="Ristic, Biljana" sort="Ristic, Biljana" uniqKey="Ristic B" first="Biljana" last="Ristic">Biljana Ristic</name>
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<name sortKey="Arsikin, Katarina" sort="Arsikin, Katarina" uniqKey="Arsikin K" first="Katarina" last="Arsikin">Katarina Arsikin</name>
<name sortKey="Bogdanovic, Andrija" sort="Bogdanovic, Andrija" uniqKey="Bogdanovic A" first="Andrija" last="Bogdanovic">Andrija Bogdanovic</name>
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<name sortKey="Bumbasirevic, Vladimir" sort="Bumbasirevic, Vladimir" uniqKey="Bumbasirevic V" first="Vladimir" last="Bumbasirevic">Vladimir Bumbasirevic</name>
<name sortKey="Harhaji Trajkovic, Ljubica" sort="Harhaji Trajkovic, Ljubica" uniqKey="Harhaji Trajkovic L" first="Ljubica" last="Harhaji-Trajkovic">Ljubica Harhaji-Trajkovic</name>
<name sortKey="Kravic Stevovic, Tamara" sort="Kravic Stevovic, Tamara" uniqKey="Kravic Stevovic T" first="Tamara" last="Kravic-Stevovic">Tamara Kravic-Stevovic</name>
<name sortKey="Martinovic, Tamara" sort="Martinovic, Tamara" uniqKey="Martinovic T" first="Tamara" last="Martinovic">Tamara Martinovic</name>
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<name sortKey="Perovic, Vladimir" sort="Perovic, Vladimir" uniqKey="Perovic V" first="Vladimir" last="Perovic">Vladimir Perovic</name>
<name sortKey="Suzin Zivkovic, Violeta" sort="Suzin Zivkovic, Violeta" uniqKey="Suzin Zivkovic V" first="Violeta" last="Suzin-Zivkovic">Violeta Suzin-Zivkovic</name>
<name sortKey="Trajkovic, Vladimir" sort="Trajkovic, Vladimir" uniqKey="Trajkovic V" first="Vladimir" last="Trajkovic">Vladimir Trajkovic</name>
</country>
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Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells.

Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells.

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