Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma
Summary Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. D...
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| Veröffentlicht in: | British journal of haematology 2004-04, Vol.125 (2), p.156-161 |
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| creator | Khan, S. B. Maududi, T. Barton, K. Ayers, J. Alkan, S. |
| description | Summary
Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)‐6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL‐2 family proteins (BCL‐2, BCL‐XL, BAX and MCL‐1) were also investigated. In addition, the RPMI 8226 cell line (IL‐6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time‐ and dose‐dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL‐2, BCL‐XL and MCL‐1 showed decreased expression in depsipeptide‐treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM. |
| doi_str_mv | 10.1111/j.1365-2141.2004.04882.x |
| format | Article |
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Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)‐6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL‐2 family proteins (BCL‐2, BCL‐XL, BAX and MCL‐1) were also investigated. In addition, the RPMI 8226 cell line (IL‐6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time‐ and dose‐dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL‐2, BCL‐XL and MCL‐1 showed decreased expression in depsipeptide‐treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/j.1365-2141.2004.04882.x</identifier><identifier>PMID: 15059137</identifier><identifier>CODEN: BJHEAL</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Antibiotics, Antineoplastic - therapeutic use ; apoptosis ; Apoptosis - drug effects ; bcl-2-Associated X Protein ; bcl-X Protein ; Biological and medical sciences ; Cell Line, Tumor ; depsipeptide ; Depsipeptides ; Flow Cytometry ; Hematologic and hematopoietic diseases ; Hematology ; histone deacytylase inhibitors ; Humans ; Immunodeficiencies. Immunoglobulinopathies ; Immunoglobulinopathies ; Immunopathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical sciences ; Middle Aged ; multiple myeloma ; Multiple Myeloma - drug therapy ; Multiple Myeloma - pathology ; Peptides, Cyclic - therapeutic use ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Recurrence ; U266</subject><ispartof>British journal of haematology, 2004-04, Vol.125 (2), p.156-161</ispartof><rights>2004 INIST-CNRS</rights><rights>Copyright Blackwell Scientific Publications Ltd. Apr 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5382-fbdfcb7d4a04ebd09c01e79064656dc7be68bfd9c628bca0e7a2f422546711df3</citedby><cites>FETCH-LOGICAL-c5382-fbdfcb7d4a04ebd09c01e79064656dc7be68bfd9c628bca0e7a2f422546711df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1365-2141.2004.04882.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1365-2141.2004.04882.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27903,27904,45553,45554,46388,46812</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15624213$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15059137$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khan, S. B.</creatorcontrib><creatorcontrib>Maududi, T.</creatorcontrib><creatorcontrib>Barton, K.</creatorcontrib><creatorcontrib>Ayers, J.</creatorcontrib><creatorcontrib>Alkan, S.</creatorcontrib><title>Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)‐6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL‐2 family proteins (BCL‐2, BCL‐XL, BAX and MCL‐1) were also investigated. In addition, the RPMI 8226 cell line (IL‐6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time‐ and dose‐dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL‐2, BCL‐XL and MCL‐1 showed decreased expression in depsipeptide‐treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM.</description><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein</subject><subject>bcl-X Protein</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>depsipeptide</subject><subject>Depsipeptides</subject><subject>Flow Cytometry</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>histone deacytylase inhibitors</subject><subject>Humans</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>multiple myeloma</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - pathology</subject><subject>Peptides, Cyclic - therapeutic use</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Recurrence</subject><subject>U266</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkN9r1TAUx8NQtuvcvzDCQJiw1nPStGkf9jCHc8pAEH01pMkJy6W_bHpx_e9tvZfpo3lJOOdzvpx8GOMIKS7n3TbFrMgTgRJTASBTkGUp0qcjtnluvGAbAFAJLr0T9irGLQBmkOMxO8Ec8goztWE_bjrTzDFE3nv-GOLUd8QdGUvT3JhIPHSPoQ5TP14t5SGGgYYpOOKXd18rQCHKt1ecvCc78b7j7a6ZwtAQb2dq-ta8Zi-9aSKdHe5T9v3uw7fb--Thy8dPtzcPic2zUiS-dt7WykkDkmoHlQUkVUEhi7xwVtVUlLV3lS1EWVsDpIzwUohcFgrR-eyUXexzh7H_uaM46W2_G5evRY1VmSupZLVA5R6yYx_jSF4PY2jNOGsEvXrVW73q06s-vXrVf7zqp2X0_JC_q1tyfwcPIhfgzQEw0ZrGj6azIf7DFUIKzBbues_9Cg3N_72Afv_5fn1lvwHUlpKp</recordid><startdate>200404</startdate><enddate>200404</enddate><creator>Khan, S. B.</creator><creator>Maududi, T.</creator><creator>Barton, K.</creator><creator>Ayers, J.</creator><creator>Alkan, S.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><general>Blackwell Publishing Ltd</general><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>7T5</scope><scope>H94</scope></search><sort><creationdate>200404</creationdate><title>Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma</title><author>Khan, S. B. ; Maududi, T. ; Barton, K. ; Ayers, J. ; Alkan, S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5382-fbdfcb7d4a04ebd09c01e79064656dc7be68bfd9c628bca0e7a2f422546711df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antibiotics, Antineoplastic - therapeutic use</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>bcl-2-Associated X Protein</topic><topic>bcl-X Protein</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>depsipeptide</topic><topic>Depsipeptides</topic><topic>Flow Cytometry</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>histone deacytylase inhibitors</topic><topic>Humans</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>multiple myeloma</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - pathology</topic><topic>Peptides, Cyclic - therapeutic use</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Recurrence</topic><topic>U266</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khan, S. B.</creatorcontrib><creatorcontrib>Maududi, T.</creatorcontrib><creatorcontrib>Barton, K.</creatorcontrib><creatorcontrib>Ayers, J.</creatorcontrib><creatorcontrib>Alkan, S.</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>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khan, S. B.</au><au>Maududi, T.</au><au>Barton, K.</au><au>Ayers, J.</au><au>Alkan, S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2004-04</date><risdate>2004</risdate><volume>125</volume><issue>2</issue><spage>156</spage><epage>161</epage><pages>156-161</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><coden>BJHEAL</coden><abstract>Summary
Multiple myeloma (MM) is a neoplastic proliferation of plasma cells and remains an incurable disease because of the development of drug resistance. Histone deacytylase (HDAC) inhibitors are a new class of chemotherapeutic reagents that cause growth arrest and apoptosis of neoplastic cells. Depsipeptide, a new member of the HDAC inhibitors, was found to be safe in humans and has been shown to induce apoptosis in various cancers. In order to evaluate the effects of depsipeptide, a MM cell line, U266 [interleukin (IL)‐6 dependent], was analysed for viability and apoptosis. The combined effect of depsipeptide with melphalan and changes in BCL‐2 family proteins (BCL‐2, BCL‐XL, BAX and MCL‐1) were also investigated. In addition, the RPMI 8226 cell line (IL‐6 independent), and primary patient myeloma cells were also analysed for apoptosis after depsipeptide treatment. Depsipeptide induced apoptosis in both U266 and RPMI 8226 cell lines in a time‐ and dose‐dependent fashion, and in primary patient myeloma cells. We also demonstrated that depsipeptide had an additive effect with melphalan (10 μmol/l). BCL‐2, BCL‐XL and MCL‐1 showed decreased expression in depsipeptide‐treated samples. Based on recent clinical trials demonstrating minimal clinical toxicity, our study supports the future clinical utilization of depsipeptide in the management of MM.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>15059137</pmid><doi>10.1111/j.1365-2141.2004.04882.x</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antibiotics, Antineoplastic - therapeutic use apoptosis Apoptosis - drug effects bcl-2-Associated X Protein bcl-X Protein Biological and medical sciences Cell Line, Tumor depsipeptide Depsipeptides Flow Cytometry Hematologic and hematopoietic diseases Hematology histone deacytylase inhibitors Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulinopathies Immunopathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical sciences Middle Aged multiple myeloma Multiple Myeloma - drug therapy Multiple Myeloma - pathology Peptides, Cyclic - therapeutic use Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins c-bcl-2 - metabolism Recurrence U266 |
| title | Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma |
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