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Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells
Background: Standard therapy for acute promyelocytic leukaemia (APL) includes retinoic acid (all- trans retinoic acid (ATRA)), which promotes differentiation of promyelocytic blasts. Although co-administration of arsenic trioxide (ATO) with ATRA has emerged as an effective option to treat APL, the m...
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| Published in: | British journal of cancer 2014-08, Vol.111 (5), p.874-882 |
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| container_end_page | 882 |
| container_issue | 5 |
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| container_title | British journal of cancer |
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| creator | Valenzuela, M Glorieux, C Stockis, J Sid, B Sandoval, J M Felipe, K B Kviecinski, M R Verrax, J Calderon, P Buc |
| description | Background:
Standard therapy for acute promyelocytic leukaemia (APL) includes retinoic acid (all-
trans
retinoic acid (ATRA)), which promotes differentiation of promyelocytic blasts. Although co-administration of arsenic trioxide (ATO) with ATRA has emerged as an effective option to treat APL, the molecular basis of this effect remains unclear.
Methods:
Four leukaemia cancer human models (HL60, THP-1, NBR4 and NBR4-R2 cells) were treated either with ATO alone or ATO plus ATRA. Cancer cell survival was monitored by trypan blue exclusion and DEVDase activity assays. Gene and protein expression changes were assessed by RT-PCR and western blot.
Results:
ATO induced an antioxidant response characterised by Nrf2 nuclear translocation and enhanced transcription of downstream target genes (that is, HO-1, NQO1, GCLM, ferritin). In cells exposed to ATO plus ATRA, the Nrf2 nuclear translocation was prevented and cytotoxicity was enhanced. HO-1 overexpression reversed partially the cytotoxicity by ATRA-ATO in HL60 cells. The inhibitory effects of ATRA on ATO-mediated responses were not observed in either the ATRA-resistant NB4-R2 cells or in NB4 cells pre-incubated with the RAR
α
antagonist Ro-41-52-53.
Conclusions:
The augmented cytotoxicity observed in leukaemia cells following combined ATO-ATRA treatment is likely due to inhibition of Nrf2 activity, thus explaining the efficacy of combined ATO-ATRA treatment in the APL therapy. |
| doi_str_mv | 10.1038/bjc.2014.380 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4150280</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3414106921</sourcerecordid><originalsourceid>FETCH-LOGICAL-c579t-4f6708ac210c1fbb4a6cfae86828fb9aa0689656591918cd0fd60d3f80d36ec73</originalsourceid><addsrcrecordid>eNptkc-LEzEcxYMobl29eZaAeHPqN5lJJnMRyuIvqC7IevIQMt9Jaspspibp4vjXm9q6ruAlIbxP3vclj5CnDJYMavWq3-KSA2uWtYJ7ZMFEzSumeHufLACgraDjcEYepbQtxw5U-5CccQFQS8kW5Otnm32YPFKDfqBpDjZu_E-b6Orqsrq2gzfZDhTnPOXph0efZ9rPdBctjvvBhw39FB0vl7O_OWg-0NXHNUU7jukxeeDMmOyT035Ovrx9c3XxvlpfvvtwsVpXKNouV42TLSiDnAEy1_eNkeiMVVJx5frOGJCqk0KKjnVM4QBukDDUTpVFWmzrc_L66Lvb9yUx2pCjGfUu-msTZz0Zr_9Vgv-mN9ONbpgArqAYPD8ZxOn73qast9M-hpJZMyEkV1xIWaiXRwrjlFK07nYCA32oQpcq9KEKXf82fXY31S385-8L8OIEmIRmdNEE9Okvp9qWN_LwvOrIpSKFjY130v1v8C-ILaFN</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1556282566</pqid></control><display><type>article</type><title>Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells</title><source>Open Access: PubMed Central</source><creator>Valenzuela, M ; Glorieux, C ; Stockis, J ; Sid, B ; Sandoval, J M ; Felipe, K B ; Kviecinski, M R ; Verrax, J ; Calderon, P Buc</creator><creatorcontrib>Valenzuela, M ; Glorieux, C ; Stockis, J ; Sid, B ; Sandoval, J M ; Felipe, K B ; Kviecinski, M R ; Verrax, J ; Calderon, P Buc</creatorcontrib><description>Background:
Standard therapy for acute promyelocytic leukaemia (APL) includes retinoic acid (all-
trans
retinoic acid (ATRA)), which promotes differentiation of promyelocytic blasts. Although co-administration of arsenic trioxide (ATO) with ATRA has emerged as an effective option to treat APL, the molecular basis of this effect remains unclear.
Methods:
Four leukaemia cancer human models (HL60, THP-1, NBR4 and NBR4-R2 cells) were treated either with ATO alone or ATO plus ATRA. Cancer cell survival was monitored by trypan blue exclusion and DEVDase activity assays. Gene and protein expression changes were assessed by RT-PCR and western blot.
Results:
ATO induced an antioxidant response characterised by Nrf2 nuclear translocation and enhanced transcription of downstream target genes (that is, HO-1, NQO1, GCLM, ferritin). In cells exposed to ATO plus ATRA, the Nrf2 nuclear translocation was prevented and cytotoxicity was enhanced. HO-1 overexpression reversed partially the cytotoxicity by ATRA-ATO in HL60 cells. The inhibitory effects of ATRA on ATO-mediated responses were not observed in either the ATRA-resistant NB4-R2 cells or in NB4 cells pre-incubated with the RAR
α
antagonist Ro-41-52-53.
Conclusions:
The augmented cytotoxicity observed in leukaemia cells following combined ATO-ATRA treatment is likely due to inhibition of Nrf2 activity, thus explaining the efficacy of combined ATO-ATRA treatment in the APL therapy.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2014.380</identifier><identifier>PMID: 25003661</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/92/609 ; 692/699/67/1990/283/1897 ; 692/700/565/1436/1437 ; Acids ; Antioxidants ; Arsenic ; Arsenicals - pharmacology ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cancer therapies ; Cell Survival - drug effects ; Cytotoxicity ; Drug Resistance ; Drug Synergism ; Drugs ; Epidemiology ; Glutathione - metabolism ; Hematologic and hematopoietic diseases ; Heme Oxygenase-1 - metabolism ; HL-60 Cells ; Humans ; Leukemia ; Leukemia, Promyelocytic, Acute - drug therapy ; Leukemia, Promyelocytic, Acute - metabolism ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical research ; Medical sciences ; Molecular Medicine ; Mortality ; NF-E2-Related Factor 2 - metabolism ; Oncology ; Oxidation ; Oxides - pharmacology ; Receptors, Retinoic Acid - genetics ; Remission (Medicine) ; Retinoic Acid Receptor alpha ; Translational Therapeutics ; Tretinoin - pharmacology ; Tumor Cells, Cultured ; Tumors</subject><ispartof>British journal of cancer, 2014-08, Vol.111 (5), p.874-882</ispartof><rights>The Author(s) 2014</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Aug 26, 2014</rights><rights>Copyright © 2014 Cancer Research UK 2014 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c579t-4f6708ac210c1fbb4a6cfae86828fb9aa0689656591918cd0fd60d3f80d36ec73</citedby><cites>FETCH-LOGICAL-c579t-4f6708ac210c1fbb4a6cfae86828fb9aa0689656591918cd0fd60d3f80d36ec73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150280/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150280/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=28772467$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25003661$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Valenzuela, M</creatorcontrib><creatorcontrib>Glorieux, C</creatorcontrib><creatorcontrib>Stockis, J</creatorcontrib><creatorcontrib>Sid, B</creatorcontrib><creatorcontrib>Sandoval, J M</creatorcontrib><creatorcontrib>Felipe, K B</creatorcontrib><creatorcontrib>Kviecinski, M R</creatorcontrib><creatorcontrib>Verrax, J</creatorcontrib><creatorcontrib>Calderon, P Buc</creatorcontrib><title>Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
Standard therapy for acute promyelocytic leukaemia (APL) includes retinoic acid (all-
trans
retinoic acid (ATRA)), which promotes differentiation of promyelocytic blasts. Although co-administration of arsenic trioxide (ATO) with ATRA has emerged as an effective option to treat APL, the molecular basis of this effect remains unclear.
Methods:
Four leukaemia cancer human models (HL60, THP-1, NBR4 and NBR4-R2 cells) were treated either with ATO alone or ATO plus ATRA. Cancer cell survival was monitored by trypan blue exclusion and DEVDase activity assays. Gene and protein expression changes were assessed by RT-PCR and western blot.
Results:
ATO induced an antioxidant response characterised by Nrf2 nuclear translocation and enhanced transcription of downstream target genes (that is, HO-1, NQO1, GCLM, ferritin). In cells exposed to ATO plus ATRA, the Nrf2 nuclear translocation was prevented and cytotoxicity was enhanced. HO-1 overexpression reversed partially the cytotoxicity by ATRA-ATO in HL60 cells. The inhibitory effects of ATRA on ATO-mediated responses were not observed in either the ATRA-resistant NB4-R2 cells or in NB4 cells pre-incubated with the RAR
α
antagonist Ro-41-52-53.
Conclusions:
The augmented cytotoxicity observed in leukaemia cells following combined ATO-ATRA treatment is likely due to inhibition of Nrf2 activity, thus explaining the efficacy of combined ATO-ATRA treatment in the APL therapy.</description><subject>631/92/609</subject><subject>692/699/67/1990/283/1897</subject><subject>692/700/565/1436/1437</subject><subject>Acids</subject><subject>Antioxidants</subject><subject>Arsenic</subject><subject>Arsenicals - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cancer therapies</subject><subject>Cell Survival - drug effects</subject><subject>Cytotoxicity</subject><subject>Drug Resistance</subject><subject>Drug Synergism</subject><subject>Drugs</subject><subject>Epidemiology</subject><subject>Glutathione - metabolism</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Leukemia, Promyelocytic, Acute - drug therapy</subject><subject>Leukemia, Promyelocytic, Acute - metabolism</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Molecular Medicine</subject><subject>Mortality</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Oncology</subject><subject>Oxidation</subject><subject>Oxides - pharmacology</subject><subject>Receptors, Retinoic Acid - genetics</subject><subject>Remission (Medicine)</subject><subject>Retinoic Acid Receptor alpha</subject><subject>Translational Therapeutics</subject><subject>Tretinoin - pharmacology</subject><subject>Tumor Cells, Cultured</subject><subject>Tumors</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><recordid>eNptkc-LEzEcxYMobl29eZaAeHPqN5lJJnMRyuIvqC7IevIQMt9Jaspspibp4vjXm9q6ruAlIbxP3vclj5CnDJYMavWq3-KSA2uWtYJ7ZMFEzSumeHufLACgraDjcEYepbQtxw5U-5CccQFQS8kW5Otnm32YPFKDfqBpDjZu_E-b6Orqsrq2gzfZDhTnPOXph0efZ9rPdBctjvvBhw39FB0vl7O_OWg-0NXHNUU7jukxeeDMmOyT035Ovrx9c3XxvlpfvvtwsVpXKNouV42TLSiDnAEy1_eNkeiMVVJx5frOGJCqk0KKjnVM4QBukDDUTpVFWmzrc_L66Lvb9yUx2pCjGfUu-msTZz0Zr_9Vgv-mN9ONbpgArqAYPD8ZxOn73qast9M-hpJZMyEkV1xIWaiXRwrjlFK07nYCA32oQpcq9KEKXf82fXY31S385-8L8OIEmIRmdNEE9Okvp9qWN_LwvOrIpSKFjY130v1v8C-ILaFN</recordid><startdate>20140826</startdate><enddate>20140826</enddate><creator>Valenzuela, M</creator><creator>Glorieux, C</creator><creator>Stockis, J</creator><creator>Sid, B</creator><creator>Sandoval, J M</creator><creator>Felipe, K B</creator><creator>Kviecinski, M R</creator><creator>Verrax, J</creator><creator>Calderon, P Buc</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20140826</creationdate><title>Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells</title><author>Valenzuela, M ; Glorieux, C ; Stockis, J ; Sid, B ; Sandoval, J M ; Felipe, K B ; Kviecinski, M R ; Verrax, J ; Calderon, P Buc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c579t-4f6708ac210c1fbb4a6cfae86828fb9aa0689656591918cd0fd60d3f80d36ec73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>631/92/609</topic><topic>692/699/67/1990/283/1897</topic><topic>692/700/565/1436/1437</topic><topic>Acids</topic><topic>Antioxidants</topic><topic>Arsenic</topic><topic>Arsenicals - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cancer therapies</topic><topic>Cell Survival - drug effects</topic><topic>Cytotoxicity</topic><topic>Drug Resistance</topic><topic>Drug Synergism</topic><topic>Drugs</topic><topic>Epidemiology</topic><topic>Glutathione - metabolism</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Leukemia, Promyelocytic, Acute - drug therapy</topic><topic>Leukemia, Promyelocytic, Acute - metabolism</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Molecular Medicine</topic><topic>Mortality</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Oncology</topic><topic>Oxidation</topic><topic>Oxides - pharmacology</topic><topic>Receptors, Retinoic Acid - genetics</topic><topic>Remission (Medicine)</topic><topic>Retinoic Acid Receptor alpha</topic><topic>Translational Therapeutics</topic><topic>Tretinoin - pharmacology</topic><topic>Tumor Cells, Cultured</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Valenzuela, M</creatorcontrib><creatorcontrib>Glorieux, C</creatorcontrib><creatorcontrib>Stockis, J</creatorcontrib><creatorcontrib>Sid, B</creatorcontrib><creatorcontrib>Sandoval, J M</creatorcontrib><creatorcontrib>Felipe, K B</creatorcontrib><creatorcontrib>Kviecinski, M R</creatorcontrib><creatorcontrib>Verrax, J</creatorcontrib><creatorcontrib>Calderon, P Buc</creatorcontrib><collection>SpringerOpen</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Valenzuela, M</au><au>Glorieux, C</au><au>Stockis, J</au><au>Sid, B</au><au>Sandoval, J M</au><au>Felipe, K B</au><au>Kviecinski, M R</au><au>Verrax, J</au><au>Calderon, P Buc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2014-08-26</date><risdate>2014</risdate><volume>111</volume><issue>5</issue><spage>874</spage><epage>882</epage><pages>874-882</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
Standard therapy for acute promyelocytic leukaemia (APL) includes retinoic acid (all-
trans
retinoic acid (ATRA)), which promotes differentiation of promyelocytic blasts. Although co-administration of arsenic trioxide (ATO) with ATRA has emerged as an effective option to treat APL, the molecular basis of this effect remains unclear.
Methods:
Four leukaemia cancer human models (HL60, THP-1, NBR4 and NBR4-R2 cells) were treated either with ATO alone or ATO plus ATRA. Cancer cell survival was monitored by trypan blue exclusion and DEVDase activity assays. Gene and protein expression changes were assessed by RT-PCR and western blot.
Results:
ATO induced an antioxidant response characterised by Nrf2 nuclear translocation and enhanced transcription of downstream target genes (that is, HO-1, NQO1, GCLM, ferritin). In cells exposed to ATO plus ATRA, the Nrf2 nuclear translocation was prevented and cytotoxicity was enhanced. HO-1 overexpression reversed partially the cytotoxicity by ATRA-ATO in HL60 cells. The inhibitory effects of ATRA on ATO-mediated responses were not observed in either the ATRA-resistant NB4-R2 cells or in NB4 cells pre-incubated with the RAR
α
antagonist Ro-41-52-53.
Conclusions:
The augmented cytotoxicity observed in leukaemia cells following combined ATO-ATRA treatment is likely due to inhibition of Nrf2 activity, thus explaining the efficacy of combined ATO-ATRA treatment in the APL therapy.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25003661</pmid><doi>10.1038/bjc.2014.380</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2014-08, Vol.111 (5), p.874-882 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4150280 |
| source | Open Access: PubMed Central |
| subjects | 631/92/609 692/699/67/1990/283/1897 692/700/565/1436/1437 Acids Antioxidants Arsenic Arsenicals - pharmacology Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Research Cancer therapies Cell Survival - drug effects Cytotoxicity Drug Resistance Drug Synergism Drugs Epidemiology Glutathione - metabolism Hematologic and hematopoietic diseases Heme Oxygenase-1 - metabolism HL-60 Cells Humans Leukemia Leukemia, Promyelocytic, Acute - drug therapy Leukemia, Promyelocytic, Acute - metabolism Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical research Medical sciences Molecular Medicine Mortality NF-E2-Related Factor 2 - metabolism Oncology Oxidation Oxides - pharmacology Receptors, Retinoic Acid - genetics Remission (Medicine) Retinoic Acid Receptor alpha Translational Therapeutics Tretinoin - pharmacology Tumor Cells, Cultured Tumors |
| title | Retinoic acid synergizes ATO-mediated cytotoxicity by precluding Nrf2 activity in AML cells |
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