Intracellular Glutathione Levels Determine Cell Sensitivity to Apoptosis Induced by the Antineoplasic Agent N-(4-hydroxyphenyl)retinamide
Background: We have previously demonstrated that the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) induces the overproduction of reactive oxygen species (ROS) in human leukemia cells, which in turn triggers the intrinsic (mitochondrial) apoptotic pathway. In order to study the role of gl...
Gespeichert in:
| Veröffentlicht in: | Anticancer research 2005-05, Vol.25 (3B), p.1945-1951 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1951 |
|---|---|
| container_issue | 3B |
| container_start_page | 1945 |
| container_title | Anticancer research |
| container_volume | 25 |
| creator | Morales, María-Celia Pérez-Yarza, Gorka Nieto-Rementeria, Naiara Boyano, María-Dolores Jangi, Muhialdin Atencia, Rafael Asumendi, Aintzane |
| description | Background: We have previously demonstrated that the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) induces the
overproduction of reactive oxygen species (ROS) in human leukemia cells, which in turn triggers the intrinsic (mitochondrial)
apoptotic pathway. In order to study the role of glutathione in 4-HPR-induced apoptosis, the levels of this antioxidant were
analyzed in cell lines which are sensitive and resistant to the effects of 4-HPR, and the effect of the modulation of glutathione
levels on 4-HPR cytotoxicity was characterized. Materials and Methods: Mitochondrial membrane potential (Îæm) and the levels
of glutathione were measured by flow cytometry. A fluorometric assay was used to measure intracellular ROS generation and
Western blot was employed to analyze tissue transglutaminase expression. Results: 4-HPR generated large quantities of ROS
in cell lines which expressed low glutathione levels, these cells being the most sensitive to the retinoid. The sensitivity
of leukemia cells to 4-HPR could be modulated, either by increasing intracellular glutathione contents using all-trans retinoic
acid (ATRA), or by decreasing it using DL-buthionine-S,R-sulfoximine (BSO). ATRA increased the level of expression of tissue
transglutaminase, whereas inhibition of this enzyme led to enhanced apoptosis. Conclusion: Our findings indicate that the
glutathione content contributes to determining the sensitivity of cells to 4-HPR and points to the potential application of
glutathione-inhibiting agents as enhancers in 4-HPR-based therapies. |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_68574152</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>68574152</sourcerecordid><originalsourceid>FETCH-LOGICAL-h270t-99149a5851b0dea92bb383d6c8e630e12a829e1c084e2db2ffc9c8ab2c21c3f13</originalsourceid><addsrcrecordid>eNpN0Mtu1DAUBuAIUdGh8ArIG1BZRPIlTuzldHphpFFZtKyjE-ekMXIutZ2WPAJvXSMGldWRfn3novMm27BKs7ySgr7NNpRLmleUytPsfQg_KS1LrcS77JSVTCrN9Sb7vR-jB4POLQ48uXFLhNjbaURywCd0gVxiRD_YFOySInc4Bhvtk40riRPZztMcp2AD2Y_tYrAlTcp7JNsxpp5pdhCsIdsHHCO5zc-LvF9bP_1a5x7H1X31mBgMtsUP2UkHLuDHYz3Lflxf3e--5YfvN_vd9pD3vKIx15oVGqSSrKEtguZNI5RoS6OwFBQZB8U1MkNVgbxteNcZbRQ03HBmRMfEWfbl79zZT48LhlgPNvx5AKRzl1CXSlYFkzzBT0e4NAO29eztAH6t_z0vgc9HAMGA6zyMxob_nKZKKvW6sbcP_bP1WIcBnEtjRQ2ey1pc1EwXUrwApVaI9w</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>68574152</pqid></control><display><type>article</type><title>Intracellular Glutathione Levels Determine Cell Sensitivity to Apoptosis Induced by the Antineoplasic Agent N-(4-hydroxyphenyl)retinamide</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Morales, María-Celia ; Pérez-Yarza, Gorka ; Nieto-Rementeria, Naiara ; Boyano, María-Dolores ; Jangi, Muhialdin ; Atencia, Rafael ; Asumendi, Aintzane</creator><creatorcontrib>Morales, María-Celia ; Pérez-Yarza, Gorka ; Nieto-Rementeria, Naiara ; Boyano, María-Dolores ; Jangi, Muhialdin ; Atencia, Rafael ; Asumendi, Aintzane</creatorcontrib><description>Background: We have previously demonstrated that the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) induces the
overproduction of reactive oxygen species (ROS) in human leukemia cells, which in turn triggers the intrinsic (mitochondrial)
apoptotic pathway. In order to study the role of glutathione in 4-HPR-induced apoptosis, the levels of this antioxidant were
analyzed in cell lines which are sensitive and resistant to the effects of 4-HPR, and the effect of the modulation of glutathione
levels on 4-HPR cytotoxicity was characterized. Materials and Methods: Mitochondrial membrane potential (Îæm) and the levels
of glutathione were measured by flow cytometry. A fluorometric assay was used to measure intracellular ROS generation and
Western blot was employed to analyze tissue transglutaminase expression. Results: 4-HPR generated large quantities of ROS
in cell lines which expressed low glutathione levels, these cells being the most sensitive to the retinoid. The sensitivity
of leukemia cells to 4-HPR could be modulated, either by increasing intracellular glutathione contents using all-trans retinoic
acid (ATRA), or by decreasing it using DL-buthionine-S,R-sulfoximine (BSO). ATRA increased the level of expression of tissue
transglutaminase, whereas inhibition of this enzyme led to enhanced apoptosis. Conclusion: Our findings indicate that the
glutathione content contributes to determining the sensitivity of cells to 4-HPR and points to the potential application of
glutathione-inhibiting agents as enhancers in 4-HPR-based therapies.</description><identifier>ISSN: 0250-7005</identifier><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 16158929</identifier><language>eng</language><publisher>Attiki: International Institute of Anticancer Research</publisher><subject>Antineoplastic Agents - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Apoptosis - drug effects ; Apoptosis - physiology ; Biological and medical sciences ; Buthionine Sulfoximine - administration & dosage ; Buthionine Sulfoximine - pharmacology ; Cadaverine - analogs & derivatives ; Cadaverine - pharmacology ; Cell Line, Tumor ; Enzyme Inhibitors - pharmacology ; Fenretinide - administration & dosage ; Fenretinide - pharmacology ; Glutathione - metabolism ; Humans ; Jurkat Cells ; Leukemia, T-Cell - drug therapy ; Leukemia, T-Cell - enzymology ; Leukemia, T-Cell - metabolism ; Leukemia, T-Cell - pathology ; Medical sciences ; Oxidative Stress - drug effects ; Transglutaminases - antagonists & inhibitors ; Transglutaminases - biosynthesis ; Transglutaminases - metabolism ; Tretinoin - administration & dosage ; Tretinoin - pharmacology ; Tumors</subject><ispartof>Anticancer research, 2005-05, Vol.25 (3B), p.1945-1951</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16908588$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16158929$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Morales, María-Celia</creatorcontrib><creatorcontrib>Pérez-Yarza, Gorka</creatorcontrib><creatorcontrib>Nieto-Rementeria, Naiara</creatorcontrib><creatorcontrib>Boyano, María-Dolores</creatorcontrib><creatorcontrib>Jangi, Muhialdin</creatorcontrib><creatorcontrib>Atencia, Rafael</creatorcontrib><creatorcontrib>Asumendi, Aintzane</creatorcontrib><title>Intracellular Glutathione Levels Determine Cell Sensitivity to Apoptosis Induced by the Antineoplasic Agent N-(4-hydroxyphenyl)retinamide</title><title>Anticancer research</title><addtitle>Anticancer Res</addtitle><description>Background: We have previously demonstrated that the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) induces the
overproduction of reactive oxygen species (ROS) in human leukemia cells, which in turn triggers the intrinsic (mitochondrial)
apoptotic pathway. In order to study the role of glutathione in 4-HPR-induced apoptosis, the levels of this antioxidant were
analyzed in cell lines which are sensitive and resistant to the effects of 4-HPR, and the effect of the modulation of glutathione
levels on 4-HPR cytotoxicity was characterized. Materials and Methods: Mitochondrial membrane potential (Îæm) and the levels
of glutathione were measured by flow cytometry. A fluorometric assay was used to measure intracellular ROS generation and
Western blot was employed to analyze tissue transglutaminase expression. Results: 4-HPR generated large quantities of ROS
in cell lines which expressed low glutathione levels, these cells being the most sensitive to the retinoid. The sensitivity
of leukemia cells to 4-HPR could be modulated, either by increasing intracellular glutathione contents using all-trans retinoic
acid (ATRA), or by decreasing it using DL-buthionine-S,R-sulfoximine (BSO). ATRA increased the level of expression of tissue
transglutaminase, whereas inhibition of this enzyme led to enhanced apoptosis. Conclusion: Our findings indicate that the
glutathione content contributes to determining the sensitivity of cells to 4-HPR and points to the potential application of
glutathione-inhibiting agents as enhancers in 4-HPR-based therapies.</description><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - physiology</subject><subject>Biological and medical sciences</subject><subject>Buthionine Sulfoximine - administration & dosage</subject><subject>Buthionine Sulfoximine - pharmacology</subject><subject>Cadaverine - analogs & derivatives</subject><subject>Cadaverine - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fenretinide - administration & dosage</subject><subject>Fenretinide - pharmacology</subject><subject>Glutathione - metabolism</subject><subject>Humans</subject><subject>Jurkat Cells</subject><subject>Leukemia, T-Cell - drug therapy</subject><subject>Leukemia, T-Cell - enzymology</subject><subject>Leukemia, T-Cell - metabolism</subject><subject>Leukemia, T-Cell - pathology</subject><subject>Medical sciences</subject><subject>Oxidative Stress - drug effects</subject><subject>Transglutaminases - antagonists & inhibitors</subject><subject>Transglutaminases - biosynthesis</subject><subject>Transglutaminases - metabolism</subject><subject>Tretinoin - administration & dosage</subject><subject>Tretinoin - pharmacology</subject><subject>Tumors</subject><issn>0250-7005</issn><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpN0Mtu1DAUBuAIUdGh8ArIG1BZRPIlTuzldHphpFFZtKyjE-ekMXIutZ2WPAJvXSMGldWRfn3novMm27BKs7ySgr7NNpRLmleUytPsfQg_KS1LrcS77JSVTCrN9Sb7vR-jB4POLQ48uXFLhNjbaURywCd0gVxiRD_YFOySInc4Bhvtk40riRPZztMcp2AD2Y_tYrAlTcp7JNsxpp5pdhCsIdsHHCO5zc-LvF9bP_1a5x7H1X31mBgMtsUP2UkHLuDHYz3Lflxf3e--5YfvN_vd9pD3vKIx15oVGqSSrKEtguZNI5RoS6OwFBQZB8U1MkNVgbxteNcZbRQ03HBmRMfEWfbl79zZT48LhlgPNvx5AKRzl1CXSlYFkzzBT0e4NAO29eztAH6t_z0vgc9HAMGA6zyMxob_nKZKKvW6sbcP_bP1WIcBnEtjRQ2ey1pc1EwXUrwApVaI9w</recordid><startdate>20050501</startdate><enddate>20050501</enddate><creator>Morales, María-Celia</creator><creator>Pérez-Yarza, Gorka</creator><creator>Nieto-Rementeria, Naiara</creator><creator>Boyano, María-Dolores</creator><creator>Jangi, Muhialdin</creator><creator>Atencia, Rafael</creator><creator>Asumendi, Aintzane</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></search><sort><creationdate>20050501</creationdate><title>Intracellular Glutathione Levels Determine Cell Sensitivity to Apoptosis Induced by the Antineoplasic Agent N-(4-hydroxyphenyl)retinamide</title><author>Morales, María-Celia ; Pérez-Yarza, Gorka ; Nieto-Rementeria, Naiara ; Boyano, María-Dolores ; Jangi, Muhialdin ; Atencia, Rafael ; Asumendi, Aintzane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h270t-99149a5851b0dea92bb383d6c8e630e12a829e1c084e2db2ffc9c8ab2c21c3f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - physiology</topic><topic>Biological and medical sciences</topic><topic>Buthionine Sulfoximine - administration & dosage</topic><topic>Buthionine Sulfoximine - pharmacology</topic><topic>Cadaverine - analogs & derivatives</topic><topic>Cadaverine - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fenretinide - administration & dosage</topic><topic>Fenretinide - pharmacology</topic><topic>Glutathione - metabolism</topic><topic>Humans</topic><topic>Jurkat Cells</topic><topic>Leukemia, T-Cell - drug therapy</topic><topic>Leukemia, T-Cell - enzymology</topic><topic>Leukemia, T-Cell - metabolism</topic><topic>Leukemia, T-Cell - pathology</topic><topic>Medical sciences</topic><topic>Oxidative Stress - drug effects</topic><topic>Transglutaminases - antagonists & inhibitors</topic><topic>Transglutaminases - biosynthesis</topic><topic>Transglutaminases - metabolism</topic><topic>Tretinoin - administration & dosage</topic><topic>Tretinoin - pharmacology</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Morales, María-Celia</creatorcontrib><creatorcontrib>Pérez-Yarza, Gorka</creatorcontrib><creatorcontrib>Nieto-Rementeria, Naiara</creatorcontrib><creatorcontrib>Boyano, María-Dolores</creatorcontrib><creatorcontrib>Jangi, Muhialdin</creatorcontrib><creatorcontrib>Atencia, Rafael</creatorcontrib><creatorcontrib>Asumendi, Aintzane</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><jtitle>Anticancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Morales, María-Celia</au><au>Pérez-Yarza, Gorka</au><au>Nieto-Rementeria, Naiara</au><au>Boyano, María-Dolores</au><au>Jangi, Muhialdin</au><au>Atencia, Rafael</au><au>Asumendi, Aintzane</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intracellular Glutathione Levels Determine Cell Sensitivity to Apoptosis Induced by the Antineoplasic Agent N-(4-hydroxyphenyl)retinamide</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2005-05-01</date><risdate>2005</risdate><volume>25</volume><issue>3B</issue><spage>1945</spage><epage>1951</epage><pages>1945-1951</pages><issn>0250-7005</issn><eissn>1791-7530</eissn><abstract>Background: We have previously demonstrated that the synthetic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR) induces the
overproduction of reactive oxygen species (ROS) in human leukemia cells, which in turn triggers the intrinsic (mitochondrial)
apoptotic pathway. In order to study the role of glutathione in 4-HPR-induced apoptosis, the levels of this antioxidant were
analyzed in cell lines which are sensitive and resistant to the effects of 4-HPR, and the effect of the modulation of glutathione
levels on 4-HPR cytotoxicity was characterized. Materials and Methods: Mitochondrial membrane potential (Îæm) and the levels
of glutathione were measured by flow cytometry. A fluorometric assay was used to measure intracellular ROS generation and
Western blot was employed to analyze tissue transglutaminase expression. Results: 4-HPR generated large quantities of ROS
in cell lines which expressed low glutathione levels, these cells being the most sensitive to the retinoid. The sensitivity
of leukemia cells to 4-HPR could be modulated, either by increasing intracellular glutathione contents using all-trans retinoic
acid (ATRA), or by decreasing it using DL-buthionine-S,R-sulfoximine (BSO). ATRA increased the level of expression of tissue
transglutaminase, whereas inhibition of this enzyme led to enhanced apoptosis. Conclusion: Our findings indicate that the
glutathione content contributes to determining the sensitivity of cells to 4-HPR and points to the potential application of
glutathione-inhibiting agents as enhancers in 4-HPR-based therapies.</abstract><cop>Attiki</cop><pub>International Institute of Anticancer Research</pub><pmid>16158929</pmid><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0250-7005 |
| ispartof | Anticancer research, 2005-05, Vol.25 (3B), p.1945-1951 |
| issn | 0250-7005 1791-7530 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68574152 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis - drug effects Apoptosis - physiology Biological and medical sciences Buthionine Sulfoximine - administration & dosage Buthionine Sulfoximine - pharmacology Cadaverine - analogs & derivatives Cadaverine - pharmacology Cell Line, Tumor Enzyme Inhibitors - pharmacology Fenretinide - administration & dosage Fenretinide - pharmacology Glutathione - metabolism Humans Jurkat Cells Leukemia, T-Cell - drug therapy Leukemia, T-Cell - enzymology Leukemia, T-Cell - metabolism Leukemia, T-Cell - pathology Medical sciences Oxidative Stress - drug effects Transglutaminases - antagonists & inhibitors Transglutaminases - biosynthesis Transglutaminases - metabolism Tretinoin - administration & dosage Tretinoin - pharmacology Tumors |
| title | Intracellular Glutathione Levels Determine Cell Sensitivity to Apoptosis Induced by the Antineoplasic Agent N-(4-hydroxyphenyl)retinamide |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-11T00%3A35%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Intracellular%20Glutathione%20Levels%20Determine%20Cell%20Sensitivity%20to%20Apoptosis%20Induced%20by%20the%20Antineoplasic%20Agent%20N-(4-hydroxyphenyl)retinamide&rft.jtitle=Anticancer%20research&rft.au=Morales,%20Mar%C3%ADa-Celia&rft.date=2005-05-01&rft.volume=25&rft.issue=3B&rft.spage=1945&rft.epage=1951&rft.pages=1945-1951&rft.issn=0250-7005&rft.eissn=1791-7530&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E68574152%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=68574152&rft_id=info:pmid/16158929&rfr_iscdi=true |