ZM-66, a New Podophyllotoxin Derivative Inhibits Proliferation and Induces Apoptosis in K562/ADM Cells
To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM. The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4×10−3 mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and ap...
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| Veröffentlicht in: | Chinese medical sciences journal 2014-09, Vol.29 (3), p.174-179 |
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| creator | Li, Ling Li, Hong-jie zhi, Jian-sheng Chen, Hong Xie, Wen-li |
| description | To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM.
The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4×10−3 mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay.
SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4×10−3 mmol/L) had significantly inhibitory effect on K562/ADM cells (all P |
| doi_str_mv | 10.1016/S1001-9294(14)60064-X |
| format | Article |
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The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4×10−3 mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay.
SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4×10−3 mmol/L) had significantly inhibitory effect on K562/ADM cells (all P<0.01). The acridine orange/propidium iodide dual staining showed that there were typical condensation of chromatin and nuclear fragmentation nuclei with red color in ZM-66 treated cells. Flow cytometric analysis showed that there was a significantly increase of apoptotic cells in K562/ADM cells after treated with ZM-66. RT-PCR showed that the p53 and bax mRNA expression levels in K562/ADM cells treated with ZM-66 at 1, 2, 4×10−3 mmol/L were higher than those in the cell without treatment. Western blot showed that the P53 and Bax protein expression levels in K562/ADM cells treated with ZM-66 at 2, 4×10−3 mmol/L were higher than those in the cell without treatment. But the P-gp protein expression level in K562/ADM cells treated with ZM-66 at 2, 4×10−3 mmol/L was gradually lower than those in the cell without treatment.
ZM-66 is able to induce cell death by apoptosis in vitro, as a result of the reverse of the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression of key factors associated with apoptosis induction.</description><identifier>ISSN: 1001-9294</identifier><identifier>DOI: 10.1016/S1001-9294(14)60064-X</identifier><identifier>PMID: 25264886</identifier><language>eng</language><publisher>China: Elsevier B.V</publisher><subject>apoptosis ; Apoptosis - drug effects ; Blotting, Western ; Cell Proliferation - drug effects ; Flow Cytometry ; Humans ; K562 Cells ; multidrug resistance ; P-glycoprotein ; podophyllotoxin ; Podophyllotoxin - analogs & derivatives ; Podophyllotoxin - chemistry ; Podophyllotoxin - pharmacology ; RNA, Messenger - genetics ; ZM-66</subject><ispartof>Chinese medical sciences journal, 2014-09, Vol.29 (3), p.174-179</ispartof><rights>2014 Chinese Academy Medical Sciences</rights><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3128-f7d3bf6e663233ff1fe7ce43ced62786fbb855a71054401f2c8d18b0515cc7a43</citedby><cites>FETCH-LOGICAL-c3128-f7d3bf6e663233ff1fe7ce43ced62786fbb855a71054401f2c8d18b0515cc7a43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.wanfangdata.com.cn/images/PeriodicalImages/cmsj-e/cmsj-e.jpg</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25264886$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ling</creatorcontrib><creatorcontrib>Li, Hong-jie</creatorcontrib><creatorcontrib>zhi, Jian-sheng</creatorcontrib><creatorcontrib>Chen, Hong</creatorcontrib><creatorcontrib>Xie, Wen-li</creatorcontrib><title>ZM-66, a New Podophyllotoxin Derivative Inhibits Proliferation and Induces Apoptosis in K562/ADM Cells</title><title>Chinese medical sciences journal</title><addtitle>Chin Med Sci J</addtitle><description>To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM.
The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4×10−3 mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay.
SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4×10−3 mmol/L) had significantly inhibitory effect on K562/ADM cells (all P<0.01). The acridine orange/propidium iodide dual staining showed that there were typical condensation of chromatin and nuclear fragmentation nuclei with red color in ZM-66 treated cells. Flow cytometric analysis showed that there was a significantly increase of apoptotic cells in K562/ADM cells after treated with ZM-66. RT-PCR showed that the p53 and bax mRNA expression levels in K562/ADM cells treated with ZM-66 at 1, 2, 4×10−3 mmol/L were higher than those in the cell without treatment. Western blot showed that the P53 and Bax protein expression levels in K562/ADM cells treated with ZM-66 at 2, 4×10−3 mmol/L were higher than those in the cell without treatment. But the P-gp protein expression level in K562/ADM cells treated with ZM-66 at 2, 4×10−3 mmol/L was gradually lower than those in the cell without treatment.
ZM-66 is able to induce cell death by apoptosis in vitro, as a result of the reverse of the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression of key factors associated with apoptosis induction.</description><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Blotting, Western</subject><subject>Cell Proliferation - drug effects</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>K562 Cells</subject><subject>multidrug resistance</subject><subject>P-glycoprotein</subject><subject>podophyllotoxin</subject><subject>Podophyllotoxin - analogs & derivatives</subject><subject>Podophyllotoxin - chemistry</subject><subject>Podophyllotoxin - pharmacology</subject><subject>RNA, Messenger - genetics</subject><subject>ZM-66</subject><issn>1001-9294</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkVFPHCEUhXmwqdb2J2h40yadCgww7JPZrLU11dakNTG-EIa5KJtZmMLMqv--6Fpf-0Ry73c4cA5Ce5R8poTKo1-UEFrN2IwfUv5REiJ5db2Fdl7H2-hdzktSFlTxt2ibCSa5UnIHuZuLSspP2OAfcI8vYxeHu8e-j2N88AGfQPJrM_o14LNw51s_ZnyZYu8dpDKOAZvQlVU3Wch4PsRhjNlnXKTfhWRH85MLvIC-z-_RG2f6DB9ezl10dfrl9-Jbdf7z69lifl7ZmjJVuaarWydByprVtXPUQWOB1xY6yRolXdsqIUxDieCcUMes6qhqiaDC2sbwehcdbO69N8GZcKuXcUqhOGq7yksNjFBOakJUIQ835JDinwnyqFc-2_JWEyBOWVMhpWJEzJqCig1qU8w5gdND8iuTHjUl-qkA_VyAfkpaU66fC9DXRbf_YjG1K-heVf_SL8DxBoASydpD0tl6COW3PoEddRf9fyz-AgswlZM</recordid><startdate>20140901</startdate><enddate>20140901</enddate><creator>Li, Ling</creator><creator>Li, Hong-jie</creator><creator>zhi, Jian-sheng</creator><creator>Chen, Hong</creator><creator>Xie, Wen-li</creator><general>Elsevier B.V</general><general>Department of Pharmacology, Logistics University of Chinese People’s Armed Police Forces, Tianjin 300309, China%Department of 0ral Pathology, Stomatological Hospital, Tianjin Medical University, Tianjin 300309, China%Department of Anatomy, Tianjin Medical University, Tianjin 300309, China</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>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>20140901</creationdate><title>ZM-66, a New Podophyllotoxin Derivative Inhibits Proliferation and Induces Apoptosis in K562/ADM Cells</title><author>Li, Ling ; Li, Hong-jie ; zhi, Jian-sheng ; Chen, Hong ; Xie, Wen-li</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3128-f7d3bf6e663233ff1fe7ce43ced62786fbb855a71054401f2c8d18b0515cc7a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Blotting, Western</topic><topic>Cell Proliferation - drug effects</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>K562 Cells</topic><topic>multidrug resistance</topic><topic>P-glycoprotein</topic><topic>podophyllotoxin</topic><topic>Podophyllotoxin - analogs & derivatives</topic><topic>Podophyllotoxin - chemistry</topic><topic>Podophyllotoxin - pharmacology</topic><topic>RNA, Messenger - genetics</topic><topic>ZM-66</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ling</creatorcontrib><creatorcontrib>Li, Hong-jie</creatorcontrib><creatorcontrib>zhi, Jian-sheng</creatorcontrib><creatorcontrib>Chen, Hong</creatorcontrib><creatorcontrib>Xie, Wen-li</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>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>Chinese medical sciences journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Ling</au><au>Li, Hong-jie</au><au>zhi, Jian-sheng</au><au>Chen, Hong</au><au>Xie, Wen-li</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ZM-66, a New Podophyllotoxin Derivative Inhibits Proliferation and Induces Apoptosis in K562/ADM Cells</atitle><jtitle>Chinese medical sciences journal</jtitle><addtitle>Chin Med Sci J</addtitle><date>2014-09-01</date><risdate>2014</risdate><volume>29</volume><issue>3</issue><spage>174</spage><epage>179</epage><pages>174-179</pages><issn>1001-9294</issn><abstract>To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM.
The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4×10−3 mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay.
SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4×10−3 mmol/L) had significantly inhibitory effect on K562/ADM cells (all P<0.01). The acridine orange/propidium iodide dual staining showed that there were typical condensation of chromatin and nuclear fragmentation nuclei with red color in ZM-66 treated cells. Flow cytometric analysis showed that there was a significantly increase of apoptotic cells in K562/ADM cells after treated with ZM-66. RT-PCR showed that the p53 and bax mRNA expression levels in K562/ADM cells treated with ZM-66 at 1, 2, 4×10−3 mmol/L were higher than those in the cell without treatment. Western blot showed that the P53 and Bax protein expression levels in K562/ADM cells treated with ZM-66 at 2, 4×10−3 mmol/L were higher than those in the cell without treatment. But the P-gp protein expression level in K562/ADM cells treated with ZM-66 at 2, 4×10−3 mmol/L was gradually lower than those in the cell without treatment.
ZM-66 is able to induce cell death by apoptosis in vitro, as a result of the reverse of the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression of key factors associated with apoptosis induction.</abstract><cop>China</cop><pub>Elsevier B.V</pub><pmid>25264886</pmid><doi>10.1016/S1001-9294(14)60064-X</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; Alma/SFX Local Collection |
| subjects | apoptosis Apoptosis - drug effects Blotting, Western Cell Proliferation - drug effects Flow Cytometry Humans K562 Cells multidrug resistance P-glycoprotein podophyllotoxin Podophyllotoxin - analogs & derivatives Podophyllotoxin - chemistry Podophyllotoxin - pharmacology RNA, Messenger - genetics ZM-66 |
| title | ZM-66, a New Podophyllotoxin Derivative Inhibits Proliferation and Induces Apoptosis in K562/ADM Cells |
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