Enalapril-induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves STAT5A
In this study, we aimed at evaluating the cytotoxic and apoptotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death. Cell viability and cytotoxicity...
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Veröffentlicht in: | Anticancer research 2012-07, Vol.32 (7), p.2885-2893 |
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creator | PURCLUTEPE, Ozlem ISKENDER, Guniz SAYDAM, Guray DEMET KIPER, Hatice TEZCANLI, Burcin SELVI, Nur BIRAY AVCI, Cigir KOSOVA, Buket ADAN GOKBULUT, Aysun SAHIN, Fahri BARAN, Usuf |
description | In this study, we aimed at evaluating the cytotoxic and apoptotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death.
Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the AnnexinV-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).
The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose- and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls.
Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia. |
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Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the AnnexinV-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).
The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose- and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls.
Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 22753752</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Angiotensin-Converting Enzyme Inhibitors - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Biological and medical sciences ; Cell proliferation ; Cytotoxicity ; Data processing ; Dose-Response Relationship, Drug ; Enalapril - pharmacology ; Gene Expression - drug effects ; Green fluorescent protein ; Hematologic and hematopoietic diseases ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute - drug therapy ; Leukemia, Promyelocytic, Acute - genetics ; Leukemia, Promyelocytic, Acute - metabolism ; Leukemia, Promyelocytic, Acute - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Polymerase chain reaction ; Salts ; Stat3 protein ; STAT3 Transcription Factor - biosynthesis ; STAT3 Transcription Factor - genetics ; STAT5 Transcription Factor - biosynthesis ; STAT5 Transcription Factor - genetics ; Transcription ; Tumor Suppressor Proteins - biosynthesis ; Tumor Suppressor Proteins - genetics ; Tumors</subject><ispartof>Anticancer research, 2012-07, Vol.32 (7), p.2885-2893</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26084385$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22753752$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>PURCLUTEPE, Ozlem</creatorcontrib><creatorcontrib>ISKENDER, Guniz</creatorcontrib><creatorcontrib>SAYDAM, Guray</creatorcontrib><creatorcontrib>DEMET KIPER, Hatice</creatorcontrib><creatorcontrib>TEZCANLI, Burcin</creatorcontrib><creatorcontrib>SELVI, Nur</creatorcontrib><creatorcontrib>BIRAY AVCI, Cigir</creatorcontrib><creatorcontrib>KOSOVA, Buket</creatorcontrib><creatorcontrib>ADAN GOKBULUT, Aysun</creatorcontrib><creatorcontrib>SAHIN, Fahri</creatorcontrib><creatorcontrib>BARAN, Usuf</creatorcontrib><title>Enalapril-induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves STAT5A</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>In this study, we aimed at evaluating the cytotoxic and apoptotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death.
Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the AnnexinV-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).
The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose- and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls.
Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia.</description><subject>Angiotensin-Converting Enzyme Inhibitors - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Cell proliferation</subject><subject>Cytotoxicity</subject><subject>Data processing</subject><subject>Dose-Response Relationship, Drug</subject><subject>Enalapril - pharmacology</subject><subject>Gene Expression - drug effects</subject><subject>Green fluorescent protein</subject><subject>Hematologic and hematopoietic diseases</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Leukemia, Promyelocytic, Acute - drug therapy</subject><subject>Leukemia, Promyelocytic, Acute - genetics</subject><subject>Leukemia, Promyelocytic, Acute - metabolism</subject><subject>Leukemia, Promyelocytic, Acute - pathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Polymerase chain reaction</subject><subject>Salts</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - biosynthesis</subject><subject>STAT3 Transcription Factor - genetics</subject><subject>STAT5 Transcription Factor - biosynthesis</subject><subject>STAT5 Transcription Factor - genetics</subject><subject>Transcription</subject><subject>Tumor Suppressor Proteins - biosynthesis</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumors</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0MtKw0AYBeBBFFurryCzEdwEJvNnbstQqhYCitZ1mM4FopNMzCSFvr0BK25dnc3H4XDO0DIXKs8EA3KOloQykglC2AJdpfRBCOdKwiVaUDoLwegSvW46HXQ_NCFrOjsZZ3HZx36MqUk4elyaaXT4ZYjt0YVojmNjcOWmT-3aRuO1CyHhbXeI4eASftuVO1ZeowuvQ3I3p1yh94fNbv2UVc-P23VZZT0VxZgJoyVRgnrDwQMUjheegdNKaMVyLo0yNs_3vqDOWm7yPXgphAJhOSsMsbBC9z-9_RC_JpfGum2SmRfpzsUp1TkByYkAkP-gFKgSiqmZ3p7otG-dredrWj0c69_LZnB3AjoZHfygO9OkP8eJLEAy-AblHnSK</recordid><startdate>20120701</startdate><enddate>20120701</enddate><creator>PURCLUTEPE, Ozlem</creator><creator>ISKENDER, Guniz</creator><creator>SAYDAM, Guray</creator><creator>DEMET KIPER, Hatice</creator><creator>TEZCANLI, Burcin</creator><creator>SELVI, Nur</creator><creator>BIRAY AVCI, Cigir</creator><creator>KOSOVA, Buket</creator><creator>ADAN GOKBULUT, Aysun</creator><creator>SAHIN, Fahri</creator><creator>BARAN, Usuf</creator><general>International Institute of Anticancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20120701</creationdate><title>Enalapril-induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves STAT5A</title><author>PURCLUTEPE, Ozlem ; ISKENDER, Guniz ; SAYDAM, Guray ; DEMET KIPER, Hatice ; TEZCANLI, Burcin ; SELVI, Nur ; BIRAY AVCI, Cigir ; KOSOVA, Buket ; ADAN GOKBULUT, Aysun ; SAHIN, Fahri ; BARAN, Usuf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p274t-7ca80972fc63f334e64f53ea97a95168c9cd11bf42edd6c1b3f877937d654c0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Angiotensin-Converting Enzyme Inhibitors - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Cell proliferation</topic><topic>Cytotoxicity</topic><topic>Data processing</topic><topic>Dose-Response Relationship, Drug</topic><topic>Enalapril - pharmacology</topic><topic>Gene Expression - drug effects</topic><topic>Green fluorescent protein</topic><topic>Hematologic and hematopoietic diseases</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Leukemia, Promyelocytic, Acute - drug therapy</topic><topic>Leukemia, Promyelocytic, Acute - genetics</topic><topic>Leukemia, Promyelocytic, Acute - metabolism</topic><topic>Leukemia, Promyelocytic, Acute - pathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><topic>Polymerase chain reaction</topic><topic>Salts</topic><topic>Stat3 protein</topic><topic>STAT3 Transcription Factor - biosynthesis</topic><topic>STAT3 Transcription Factor - genetics</topic><topic>STAT5 Transcription Factor - biosynthesis</topic><topic>STAT5 Transcription Factor - genetics</topic><topic>Transcription</topic><topic>Tumor Suppressor Proteins - biosynthesis</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>PURCLUTEPE, Ozlem</creatorcontrib><creatorcontrib>ISKENDER, Guniz</creatorcontrib><creatorcontrib>SAYDAM, Guray</creatorcontrib><creatorcontrib>DEMET KIPER, Hatice</creatorcontrib><creatorcontrib>TEZCANLI, Burcin</creatorcontrib><creatorcontrib>SELVI, Nur</creatorcontrib><creatorcontrib>BIRAY AVCI, Cigir</creatorcontrib><creatorcontrib>KOSOVA, Buket</creatorcontrib><creatorcontrib>ADAN GOKBULUT, Aysun</creatorcontrib><creatorcontrib>SAHIN, Fahri</creatorcontrib><creatorcontrib>BARAN, Usuf</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>PURCLUTEPE, Ozlem</au><au>ISKENDER, Guniz</au><au>SAYDAM, Guray</au><au>DEMET KIPER, Hatice</au><au>TEZCANLI, Burcin</au><au>SELVI, Nur</au><au>BIRAY AVCI, Cigir</au><au>KOSOVA, Buket</au><au>ADAN GOKBULUT, Aysun</au><au>SAHIN, Fahri</au><au>BARAN, Usuf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enalapril-induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves STAT5A</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2012-07-01</date><risdate>2012</risdate><volume>32</volume><issue>7</issue><spage>2885</spage><epage>2893</epage><pages>2885-2893</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>In this study, we aimed at evaluating the cytotoxic and apoptotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death.
Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the AnnexinV-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).
The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose- and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls.
Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>22753752</pmid><tpages>9</tpages></addata></record> |
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subjects | Angiotensin-Converting Enzyme Inhibitors - pharmacology Apoptosis Apoptosis - drug effects Biological and medical sciences Cell proliferation Cytotoxicity Data processing Dose-Response Relationship, Drug Enalapril - pharmacology Gene Expression - drug effects Green fluorescent protein Hematologic and hematopoietic diseases HL-60 Cells Humans Leukemia, Promyelocytic, Acute - drug therapy Leukemia, Promyelocytic, Acute - genetics Leukemia, Promyelocytic, Acute - metabolism Leukemia, Promyelocytic, Acute - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Polymerase chain reaction Salts Stat3 protein STAT3 Transcription Factor - biosynthesis STAT3 Transcription Factor - genetics STAT5 Transcription Factor - biosynthesis STAT5 Transcription Factor - genetics Transcription Tumor Suppressor Proteins - biosynthesis Tumor Suppressor Proteins - genetics Tumors |
title | Enalapril-induced Apoptosis of Acute Promyelocytic Leukaemia Cells Involves STAT5A |
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