Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines
Transferrin (Tf) conjugates of monomeric artemisinin (ART) and artemisinin dimer were synthesized. The two conjugates, ART-Tf and dimer-Tf, retained the original protein structure, and formed stable aggregates in aqueous buffer. ART-Tf induced declines in proteins involved in apoptosis (survivin), c...
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| Veröffentlicht in: | Anticancer research 2013-01, Vol.33 (1), p.123-132 |
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| creator | Gong, Yongmei Gallis, Byron M Goodlett, David R Yang, Yi Lu, Hailing Lacoste, Eric Lai, Henry Sasaki, Tomikazu |
| description | Transferrin (Tf) conjugates of monomeric artemisinin (ART) and artemisinin dimer were synthesized. The two conjugates, ART-Tf and dimer-Tf, retained the original protein structure, and formed stable aggregates in aqueous buffer. ART-Tf induced declines in proteins involved in apoptosis (survivin), cell cycling (cyclin D1), oncogenesis (c-myelocytomatosis oncogene product (c-MYC)), and dysregulated WNT signaling (beta-catenin) in both the human prostate (DU145) and breast (MCF7) cancer cell lines. Both ART-Tf and dimer-Tf induced down-regulation of survivin, c-MYC and mutated human epidermal growth factor receptor-2 (ERBB2 or HER2) in the BT474 breast cancer cell line. To our knowledge, this is the first demonstration that an ART derivative can cause a decline of ERBB2 in a human cancer cell line. Potential mechanisms for the observed effects are presented. Both transferrin conjugates strongly inhibited the growth of BT474 cells in the same concentration range that the conjugates caused declines in the levels of ERBB2, survivin, and c-MYC, while showing essentially no toxicity towards MCF10A normal breast cells. |
| format | Article |
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The two conjugates, ART-Tf and dimer-Tf, retained the original protein structure, and formed stable aggregates in aqueous buffer. ART-Tf induced declines in proteins involved in apoptosis (survivin), cell cycling (cyclin D1), oncogenesis (c-myelocytomatosis oncogene product (c-MYC)), and dysregulated WNT signaling (beta-catenin) in both the human prostate (DU145) and breast (MCF7) cancer cell lines. Both ART-Tf and dimer-Tf induced down-regulation of survivin, c-MYC and mutated human epidermal growth factor receptor-2 (ERBB2 or HER2) in the BT474 breast cancer cell line. To our knowledge, this is the first demonstration that an ART derivative can cause a decline of ERBB2 in a human cancer cell line. Potential mechanisms for the observed effects are presented. 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The two conjugates, ART-Tf and dimer-Tf, retained the original protein structure, and formed stable aggregates in aqueous buffer. ART-Tf induced declines in proteins involved in apoptosis (survivin), cell cycling (cyclin D1), oncogenesis (c-myelocytomatosis oncogene product (c-MYC)), and dysregulated WNT signaling (beta-catenin) in both the human prostate (DU145) and breast (MCF7) cancer cell lines. Both ART-Tf and dimer-Tf induced down-regulation of survivin, c-MYC and mutated human epidermal growth factor receptor-2 (ERBB2 or HER2) in the BT474 breast cancer cell line. To our knowledge, this is the first demonstration that an ART derivative can cause a decline of ERBB2 in a human cancer cell line. Potential mechanisms for the observed effects are presented. Both transferrin conjugates strongly inhibited the growth of BT474 cells in the same concentration range that the conjugates caused declines in the levels of ERBB2, survivin, and c-MYC, while showing essentially no toxicity towards MCF10A normal breast cells.</description><subject>Apoptosis - drug effects</subject><subject>Artemisinins - administration & dosage</subject><subject>Artemisinins - chemistry</subject><subject>beta Catenin - metabolism</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cyclin D1 - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Inhibitor of Apoptosis Proteins - metabolism</subject><subject>Male</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Protein Multimerization</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Transferrin - administration & dosage</subject><subject>Transferrin - chemistry</subject><subject>Wnt Signaling Pathway - drug effects</subject><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtPwzAQhC0kREvhLyAfuUSyvfEjR1SVh1SJC5wj21mjVIlTbOfAvydAOfS0mp1vV6O5IGuuG15pCWxFrnM-MKZUY-CKrAQIpTnoNXG7ENCXTKdAS7IxB0ypj9RP8TB_2IK_jk0Fxz73cXFs7M5014-Y6BSpS2hzod5Gvyw8DgMd-oj5hlwGO2S8Pc0NeX_cvW2fq_3r08v2YV8dBeel0mCM80Z0TnHovBBeQ7COc22AIUMLDUopGgAna60EyMZ4p-paciEVdLAh939_j2n6nDGXdon4E8NGnObccqFhuQRmFvTuhM5uxK49pn606av97wW-ARC5Xd8</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>Gong, Yongmei</creator><creator>Gallis, Byron M</creator><creator>Goodlett, David R</creator><creator>Yang, Yi</creator><creator>Lu, Hailing</creator><creator>Lacoste, Eric</creator><creator>Lai, Henry</creator><creator>Sasaki, Tomikazu</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>201301</creationdate><title>Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines</title><author>Gong, Yongmei ; Gallis, Byron M ; Goodlett, David R ; Yang, Yi ; Lu, Hailing ; Lacoste, Eric ; Lai, Henry ; Sasaki, Tomikazu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-7388bc82db613dc22c73fab117830e0ea39e552933b547623598cb644512563d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Apoptosis - drug effects</topic><topic>Artemisinins - administration & dosage</topic><topic>Artemisinins - chemistry</topic><topic>beta Catenin - metabolism</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Cyclin D1 - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Inhibitor of Apoptosis Proteins - metabolism</topic><topic>Male</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Protein Multimerization</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Transferrin - administration & dosage</topic><topic>Transferrin - chemistry</topic><topic>Wnt Signaling Pathway - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gong, Yongmei</creatorcontrib><creatorcontrib>Gallis, Byron M</creatorcontrib><creatorcontrib>Goodlett, David R</creatorcontrib><creatorcontrib>Yang, Yi</creatorcontrib><creatorcontrib>Lu, Hailing</creatorcontrib><creatorcontrib>Lacoste, Eric</creatorcontrib><creatorcontrib>Lai, Henry</creatorcontrib><creatorcontrib>Sasaki, Tomikazu</creatorcontrib><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>Gong, Yongmei</au><au>Gallis, Byron M</au><au>Goodlett, David R</au><au>Yang, Yi</au><au>Lu, Hailing</au><au>Lacoste, Eric</au><au>Lai, Henry</au><au>Sasaki, Tomikazu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2013-01</date><risdate>2013</risdate><volume>33</volume><issue>1</issue><spage>123</spage><epage>132</epage><pages>123-132</pages><eissn>1791-7530</eissn><abstract>Transferrin (Tf) conjugates of monomeric artemisinin (ART) and artemisinin dimer were synthesized. The two conjugates, ART-Tf and dimer-Tf, retained the original protein structure, and formed stable aggregates in aqueous buffer. ART-Tf induced declines in proteins involved in apoptosis (survivin), cell cycling (cyclin D1), oncogenesis (c-myelocytomatosis oncogene product (c-MYC)), and dysregulated WNT signaling (beta-catenin) in both the human prostate (DU145) and breast (MCF7) cancer cell lines. Both ART-Tf and dimer-Tf induced down-regulation of survivin, c-MYC and mutated human epidermal growth factor receptor-2 (ERBB2 or HER2) in the BT474 breast cancer cell line. To our knowledge, this is the first demonstration that an ART derivative can cause a decline of ERBB2 in a human cancer cell line. Potential mechanisms for the observed effects are presented. Both transferrin conjugates strongly inhibited the growth of BT474 cells in the same concentration range that the conjugates caused declines in the levels of ERBB2, survivin, and c-MYC, while showing essentially no toxicity towards MCF10A normal breast cells.</abstract><cop>Greece</cop><pmid>23267137</pmid><tpages>10</tpages></addata></record> |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
| subjects | Apoptosis - drug effects Artemisinins - administration & dosage Artemisinins - chemistry beta Catenin - metabolism Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - metabolism Cell Line, Tumor Cell Proliferation - drug effects Cyclin D1 - metabolism Female Humans Inhibitor of Apoptosis Proteins - metabolism Male Prostatic Neoplasms - drug therapy Prostatic Neoplasms - genetics Prostatic Neoplasms - metabolism Protein Multimerization Proto-Oncogene Proteins c-myc - metabolism Receptor, ErbB-2 - metabolism Transferrin - administration & dosage Transferrin - chemistry Wnt Signaling Pathway - drug effects |
| title | Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines |
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