OSU-03012 sensitizes TIB-196 myeloma cells to imatinib mesylate via AMP-activated protein kinase and STAT3 pathways
Abstract Although c-Kit is expressed on the surface of myeloma cells in one-third of myeloma patients, the efficacy of imatinib mesylate for patients with myeloma is still controversial. To investigate the combinatorial effect of OSU-03012 and imatinib mesylate, we treated a c-Kit-expressing myeloma...
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| Veröffentlicht in: | Leukemia research 2010-06, Vol.34 (6), p.816-820 |
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| creator | Bai, Li-Yuan Weng, Jing-Ru Tsai, Chen-Hsun Sargeant, Aaron Lin, Cheng-Wen Chiu, Chang-Fang |
| description | Abstract Although c-Kit is expressed on the surface of myeloma cells in one-third of myeloma patients, the efficacy of imatinib mesylate for patients with myeloma is still controversial. To investigate the combinatorial effect of OSU-03012 and imatinib mesylate, we treated a c-Kit-expressing myeloma cell line, TIB-196, with DMSO, OSU-03012 alone, imatinib mesylate alone and OSU-03012 plus imatinib mesylate. OSU-03012 sensitized TIB-196 cells to imatinib mesylate cytotoxicity. p-STAT3 (Tyr705), as well as down-stream cyclin D1 and Mcl-1, was down regulated. Additionally, there was markedly increased p-AMPK (Thr172) and down-regulation of p-p70S6K (Thr386) in the combination group. Combined treatments targeting c-Kit, AMPK and STAT3 may be a potential strategy for treating patients with myeloma. |
| doi_str_mv | 10.1016/j.leukres.2009.11.014 |
| format | Article |
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To investigate the combinatorial effect of OSU-03012 and imatinib mesylate, we treated a c-Kit-expressing myeloma cell line, TIB-196, with DMSO, OSU-03012 alone, imatinib mesylate alone and OSU-03012 plus imatinib mesylate. OSU-03012 sensitized TIB-196 cells to imatinib mesylate cytotoxicity. p-STAT3 (Tyr705), as well as down-stream cyclin D1 and Mcl-1, was down regulated. Additionally, there was markedly increased p-AMPK (Thr172) and down-regulation of p-p70S6K (Thr386) in the combination group. Combined treatments targeting c-Kit, AMPK and STAT3 may be a potential strategy for treating patients with myeloma.</description><identifier>ISSN: 0145-2126</identifier><identifier>EISSN: 1873-5835</identifier><identifier>DOI: 10.1016/j.leukres.2009.11.014</identifier><identifier>PMID: 20006997</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>AMP-Activated Protein Kinases - metabolism ; AMP-Activated Protein Kinases - physiology ; AMPK ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Benzamides ; Cell Line, Tumor ; Dose-Response Relationship, Drug ; Drug Evaluation, Preclinical ; Drug Resistance, Neoplasm - drug effects ; Drug Synergism ; Hematology, Oncology and Palliative Medicine ; HL-60 Cells ; Humans ; Imatinib Mesylate ; Multiple Myeloma - drug therapy ; Multiple Myeloma - metabolism ; Multiple Myeloma - pathology ; Myeloma ; OSU-03012 ; Piperazines - administration & dosage ; Protein Kinase Inhibitors - pharmacology ; Pyrazoles - administration & dosage ; Pyrazoles - pharmacology ; Pyrimidines - administration & dosage ; Signal Transduction - drug effects ; STAT3 ; STAT3 Transcription Factor - metabolism ; STAT3 Transcription Factor - physiology ; Sulfonamides - administration & dosage ; Sulfonamides - pharmacology ; Time Factors</subject><ispartof>Leukemia research, 2010-06, Vol.34 (6), p.816-820</ispartof><rights>Elsevier Ltd</rights><rights>2009 Elsevier Ltd</rights><rights>Copyright 2009 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-3ff50bd4d2ba77fb90bdeb4a9c270843de064128fdb80dbac32644ceb2473c283</citedby><cites>FETCH-LOGICAL-c451t-3ff50bd4d2ba77fb90bdeb4a9c270843de064128fdb80dbac32644ceb2473c283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0145212609005360$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20006997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bai, Li-Yuan</creatorcontrib><creatorcontrib>Weng, Jing-Ru</creatorcontrib><creatorcontrib>Tsai, Chen-Hsun</creatorcontrib><creatorcontrib>Sargeant, Aaron</creatorcontrib><creatorcontrib>Lin, Cheng-Wen</creatorcontrib><creatorcontrib>Chiu, Chang-Fang</creatorcontrib><title>OSU-03012 sensitizes TIB-196 myeloma cells to imatinib mesylate via AMP-activated protein kinase and STAT3 pathways</title><title>Leukemia research</title><addtitle>Leuk Res</addtitle><description>Abstract Although c-Kit is expressed on the surface of myeloma cells in one-third of myeloma patients, the efficacy of imatinib mesylate for patients with myeloma is still controversial. To investigate the combinatorial effect of OSU-03012 and imatinib mesylate, we treated a c-Kit-expressing myeloma cell line, TIB-196, with DMSO, OSU-03012 alone, imatinib mesylate alone and OSU-03012 plus imatinib mesylate. OSU-03012 sensitized TIB-196 cells to imatinib mesylate cytotoxicity. p-STAT3 (Tyr705), as well as down-stream cyclin D1 and Mcl-1, was down regulated. Additionally, there was markedly increased p-AMPK (Thr172) and down-regulation of p-p70S6K (Thr386) in the combination group. Combined treatments targeting c-Kit, AMPK and STAT3 may be a potential strategy for treating patients with myeloma.</description><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>AMP-Activated Protein Kinases - physiology</subject><subject>AMPK</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Benzamides</subject><subject>Cell Line, Tumor</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drug Synergism</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>HL-60 Cells</subject><subject>Humans</subject><subject>Imatinib Mesylate</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - metabolism</subject><subject>Multiple Myeloma - pathology</subject><subject>Myeloma</subject><subject>OSU-03012</subject><subject>Piperazines - administration & dosage</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Pyrazoles - administration & dosage</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyrimidines - administration & dosage</subject><subject>Signal Transduction - drug effects</subject><subject>STAT3</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>STAT3 Transcription Factor - physiology</subject><subject>Sulfonamides - administration & dosage</subject><subject>Sulfonamides - pharmacology</subject><subject>Time Factors</subject><issn>0145-2126</issn><issn>1873-5835</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkkmPEzEQhS0EYsLATwD5xqmb8tKLL6AwYhlp0CAlc7bcdrVw0ktoO0HNr8etBA5c5mS59KrKft8j5DWDnAEr3-3yDo_7CUPOAVTOWA5MPiErVlciK2pRPCWrVCkyznh5RV6EsAOAQjH1nFylFiiVqlYk3G8eMhDAOA04BB_9bwx0e_sxY6qk_Yzd2BtqsesCjSP1vYl-8A3tMcydiUhP3tD1t--ZsdGfUsHRwzRG9APd-8EEpGZwdLNdbwU9mPjjl5nDS_KsNV3AV5fzmjx8_rS9-Zrd3X-5vVnfZVYWLGaibQtonHS8MVXVNipdsJFGWV5BLYVDKCXjdeuaGlxjrOCllBYbLitheS2uydvz3PSin0cMUfc-LF8xA47HoOtagCxryR5VVkKw5KlalMVZaacxhAlbfZiSKdOsGegFjN7pCxi9gNGM6YQh9b25bDg2Pbp_XX9JJMGHswCTIyePkw7W42DR-Qlt1G70j654_98E2yVW1nR7nDHsxuM0JLs104Fr0JslHUs4QKVciBLEH82dtXM</recordid><startdate>20100601</startdate><enddate>20100601</enddate><creator>Bai, Li-Yuan</creator><creator>Weng, Jing-Ru</creator><creator>Tsai, Chen-Hsun</creator><creator>Sargeant, Aaron</creator><creator>Lin, Cheng-Wen</creator><creator>Chiu, Chang-Fang</creator><general>Elsevier Ltd</general><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>7X8</scope><scope>7T5</scope><scope>H94</scope></search><sort><creationdate>20100601</creationdate><title>OSU-03012 sensitizes TIB-196 myeloma cells to imatinib mesylate via AMP-activated protein kinase and STAT3 pathways</title><author>Bai, Li-Yuan ; Weng, Jing-Ru ; Tsai, Chen-Hsun ; Sargeant, Aaron ; Lin, Cheng-Wen ; Chiu, Chang-Fang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-3ff50bd4d2ba77fb90bdeb4a9c270843de064128fdb80dbac32644ceb2473c283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>AMP-Activated Protein Kinases - physiology</topic><topic>AMPK</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Benzamides</topic><topic>Cell Line, Tumor</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Drug Synergism</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>HL-60 Cells</topic><topic>Humans</topic><topic>Imatinib Mesylate</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - metabolism</topic><topic>Multiple Myeloma - pathology</topic><topic>Myeloma</topic><topic>OSU-03012</topic><topic>Piperazines - administration & dosage</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Pyrazoles - administration & dosage</topic><topic>Pyrazoles - pharmacology</topic><topic>Pyrimidines - administration & dosage</topic><topic>Signal Transduction - drug effects</topic><topic>STAT3</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>STAT3 Transcription Factor - physiology</topic><topic>Sulfonamides - administration & dosage</topic><topic>Sulfonamides - pharmacology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bai, Li-Yuan</creatorcontrib><creatorcontrib>Weng, Jing-Ru</creatorcontrib><creatorcontrib>Tsai, Chen-Hsun</creatorcontrib><creatorcontrib>Sargeant, Aaron</creatorcontrib><creatorcontrib>Lin, Cheng-Wen</creatorcontrib><creatorcontrib>Chiu, Chang-Fang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Leukemia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bai, Li-Yuan</au><au>Weng, Jing-Ru</au><au>Tsai, Chen-Hsun</au><au>Sargeant, Aaron</au><au>Lin, Cheng-Wen</au><au>Chiu, Chang-Fang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>OSU-03012 sensitizes TIB-196 myeloma cells to imatinib mesylate via AMP-activated protein kinase and STAT3 pathways</atitle><jtitle>Leukemia research</jtitle><addtitle>Leuk Res</addtitle><date>2010-06-01</date><risdate>2010</risdate><volume>34</volume><issue>6</issue><spage>816</spage><epage>820</epage><pages>816-820</pages><issn>0145-2126</issn><eissn>1873-5835</eissn><abstract>Abstract Although c-Kit is expressed on the surface of myeloma cells in one-third of myeloma patients, the efficacy of imatinib mesylate for patients with myeloma is still controversial. To investigate the combinatorial effect of OSU-03012 and imatinib mesylate, we treated a c-Kit-expressing myeloma cell line, TIB-196, with DMSO, OSU-03012 alone, imatinib mesylate alone and OSU-03012 plus imatinib mesylate. OSU-03012 sensitized TIB-196 cells to imatinib mesylate cytotoxicity. p-STAT3 (Tyr705), as well as down-stream cyclin D1 and Mcl-1, was down regulated. Additionally, there was markedly increased p-AMPK (Thr172) and down-regulation of p-p70S6K (Thr386) in the combination group. Combined treatments targeting c-Kit, AMPK and STAT3 may be a potential strategy for treating patients with myeloma.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>20006997</pmid><doi>10.1016/j.leukres.2009.11.014</doi><tpages>5</tpages></addata></record> |
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| subjects | AMP-Activated Protein Kinases - metabolism AMP-Activated Protein Kinases - physiology AMPK Antineoplastic Combined Chemotherapy Protocols - therapeutic use Benzamides Cell Line, Tumor Dose-Response Relationship, Drug Drug Evaluation, Preclinical Drug Resistance, Neoplasm - drug effects Drug Synergism Hematology, Oncology and Palliative Medicine HL-60 Cells Humans Imatinib Mesylate Multiple Myeloma - drug therapy Multiple Myeloma - metabolism Multiple Myeloma - pathology Myeloma OSU-03012 Piperazines - administration & dosage Protein Kinase Inhibitors - pharmacology Pyrazoles - administration & dosage Pyrazoles - pharmacology Pyrimidines - administration & dosage Signal Transduction - drug effects STAT3 STAT3 Transcription Factor - metabolism STAT3 Transcription Factor - physiology Sulfonamides - administration & dosage Sulfonamides - pharmacology Time Factors |
| title | OSU-03012 sensitizes TIB-196 myeloma cells to imatinib mesylate via AMP-activated protein kinase and STAT3 pathways |
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