Co-treatment with BEZ235 Enhances Sensitivity of BRCA1-negative Breast Cancer Cells to Olaparib
The poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib has been reported as having preferential anti-proliferative effects on breast cancer 1 (BRCA1)-deficient breast and ovarian cancer cells and was recently approved by the US Food and Drug Administration (FDA) for advanced, BRCA1-mutated ovari...
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| Veröffentlicht in: | Anticancer research 2015-07, Vol.35 (7), p.3829-3838 |
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| container_title | Anticancer research |
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| creator | Yi, Yong Weon Park, Jeong-Soo Kwak, Sahng-June Seong, Yeon-Sun |
| description | The poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib has been reported as having preferential anti-proliferative effects on breast cancer 1 (BRCA1)-deficient breast and ovarian cancer cells and was recently approved by the US Food and Drug Administration (FDA) for advanced, BRCA1-mutated ovarian cancer. Herein, we show that BEZ235, a protein kinase inhibitor, enhanced the tumor cell-killing effect of olaparib in BRCA1-mutated breast cancer cells in vitro. BEZ235 reduced olaparib-induced phosphorylation of p53 binding protein 1 (53BP1) and 53BP1 foci formation, as well as phosphorylation of AKT (S473). Long-term colony-formation assay revealed more strong synergistic effects of this combination in SUM149PT and MDA-MB-468 breast cancer cell lines. BEZ235 treatment combined with olaparib may be a candidate for effective therapeutic treatment of BRCA1-mutated breast cancer. |
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Herein, we show that BEZ235, a protein kinase inhibitor, enhanced the tumor cell-killing effect of olaparib in BRCA1-mutated breast cancer cells in vitro. BEZ235 reduced olaparib-induced phosphorylation of p53 binding protein 1 (53BP1) and 53BP1 foci formation, as well as phosphorylation of AKT (S473). Long-term colony-formation assay revealed more strong synergistic effects of this combination in SUM149PT and MDA-MB-468 breast cancer cell lines. BEZ235 treatment combined with olaparib may be a candidate for effective therapeutic treatment of BRCA1-mutated breast cancer.</description><identifier>EISSN: 1791-7530</identifier><identifier>PMID: 26124328</identifier><language>eng</language><publisher>Greece</publisher><subject><![CDATA[Antineoplastic Agents - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; BRCA1 Protein - metabolism ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; Cell Line, Tumor ; Enzyme Inhibitors - administration & dosage ; Female ; Humans ; Imidazoles - administration & dosage ; Intracellular Signaling Peptides and Proteins - metabolism ; Phosphorylation - drug effects ; Phthalazines - administration & dosage ; Piperazines - administration & dosage ; Poly(ADP-ribose) Polymerases - metabolism ; Proto-Oncogene Proteins c-akt - metabolism ; Quinolines - administration & dosage ; Receptor, ErbB-2 - metabolism ; Tumor Suppressor p53-Binding Protein 1]]></subject><ispartof>Anticancer research, 2015-07, Vol.35 (7), p.3829-3838</ispartof><rights>Copyright© 2015 International Institute of Anticancer Research (Dr. John G. 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Herein, we show that BEZ235, a protein kinase inhibitor, enhanced the tumor cell-killing effect of olaparib in BRCA1-mutated breast cancer cells in vitro. BEZ235 reduced olaparib-induced phosphorylation of p53 binding protein 1 (53BP1) and 53BP1 foci formation, as well as phosphorylation of AKT (S473). Long-term colony-formation assay revealed more strong synergistic effects of this combination in SUM149PT and MDA-MB-468 breast cancer cell lines. BEZ235 treatment combined with olaparib may be a candidate for effective therapeutic treatment of BRCA1-mutated breast cancer.</description><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>BRCA1 Protein - metabolism</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Enzyme Inhibitors - administration & dosage</subject><subject>Female</subject><subject>Humans</subject><subject>Imidazoles - administration & dosage</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Phosphorylation - drug effects</subject><subject>Phthalazines - administration & dosage</subject><subject>Piperazines - administration & dosage</subject><subject>Poly(ADP-ribose) Polymerases - metabolism</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Quinolines - administration & dosage</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Tumor Suppressor p53-Binding Protein 1</subject><issn>1791-7530</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kE1LxDAYhIMg7rr6FyRHL4UmaZLmuC31AxYW_Lh4KW_bN26kXzapsv_eiutpYHhmGOaMrJk2LNJSxCty6f1HHCtlUnFBVlwxngierkmZD1GYEEKHfaDfLhxoVrxxIWnRH6Cv0dNn7L0L7suFIx0szZ7yLYt6fIfFQ5otYR9o_stONMe29TQMdN_CCJOrrsi5hdbj9Uk35PWueMkfot3-_jHf7qKRMxYiLTjwWmClUgMAOrW6Mo2SYJtKSR43Ups0Ro2qhgWzYIyEpDZKWG6aRooNuf3rHafhc0Yfys75elkDPQ6zL5kyXEspZLKgNyd0rjpsynFyHUzH8v8U8QNALFxG</recordid><startdate>201507</startdate><enddate>201507</enddate><creator>Yi, Yong Weon</creator><creator>Park, Jeong-Soo</creator><creator>Kwak, Sahng-June</creator><creator>Seong, Yeon-Sun</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>201507</creationdate><title>Co-treatment with BEZ235 Enhances Sensitivity of BRCA1-negative Breast Cancer Cells to Olaparib</title><author>Yi, Yong Weon ; Park, Jeong-Soo ; Kwak, Sahng-June ; Seong, Yeon-Sun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p211t-732a2c3eb689aaa78f7b9d65afdb6520d57980e7e6cac3efa995a4c963f29dd53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>BRCA1 Protein - metabolism</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Enzyme Inhibitors - administration & dosage</topic><topic>Female</topic><topic>Humans</topic><topic>Imidazoles - administration & dosage</topic><topic>Intracellular Signaling Peptides and Proteins - metabolism</topic><topic>Phosphorylation - drug effects</topic><topic>Phthalazines - administration & dosage</topic><topic>Piperazines - administration & dosage</topic><topic>Poly(ADP-ribose) Polymerases - metabolism</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Quinolines - administration & dosage</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Tumor Suppressor p53-Binding Protein 1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yi, Yong Weon</creatorcontrib><creatorcontrib>Park, Jeong-Soo</creatorcontrib><creatorcontrib>Kwak, Sahng-June</creatorcontrib><creatorcontrib>Seong, Yeon-Sun</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>Yi, Yong Weon</au><au>Park, Jeong-Soo</au><au>Kwak, Sahng-June</au><au>Seong, Yeon-Sun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Co-treatment with BEZ235 Enhances Sensitivity of BRCA1-negative Breast Cancer Cells to Olaparib</atitle><jtitle>Anticancer research</jtitle><addtitle>Anticancer Res</addtitle><date>2015-07</date><risdate>2015</risdate><volume>35</volume><issue>7</issue><spage>3829</spage><epage>3838</epage><pages>3829-3838</pages><eissn>1791-7530</eissn><abstract>The poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib has been reported as having preferential anti-proliferative effects on breast cancer 1 (BRCA1)-deficient breast and ovarian cancer cells and was recently approved by the US Food and Drug Administration (FDA) for advanced, BRCA1-mutated ovarian cancer. Herein, we show that BEZ235, a protein kinase inhibitor, enhanced the tumor cell-killing effect of olaparib in BRCA1-mutated breast cancer cells in vitro. BEZ235 reduced olaparib-induced phosphorylation of p53 binding protein 1 (53BP1) and 53BP1 foci formation, as well as phosphorylation of AKT (S473). Long-term colony-formation assay revealed more strong synergistic effects of this combination in SUM149PT and MDA-MB-468 breast cancer cell lines. BEZ235 treatment combined with olaparib may be a candidate for effective therapeutic treatment of BRCA1-mutated breast cancer.</abstract><cop>Greece</cop><pmid>26124328</pmid><tpages>10</tpages></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antineoplastic Agents - administration & dosage Antineoplastic Combined Chemotherapy Protocols - pharmacology BRCA1 Protein - metabolism Breast Neoplasms - drug therapy Breast Neoplasms - metabolism Cell Line, Tumor Enzyme Inhibitors - administration & dosage Female Humans Imidazoles - administration & dosage Intracellular Signaling Peptides and Proteins - metabolism Phosphorylation - drug effects Phthalazines - administration & dosage Piperazines - administration & dosage Poly(ADP-ribose) Polymerases - metabolism Proto-Oncogene Proteins c-akt - metabolism Quinolines - administration & dosage Receptor, ErbB-2 - metabolism Tumor Suppressor p53-Binding Protein 1 |
| title | Co-treatment with BEZ235 Enhances Sensitivity of BRCA1-negative Breast Cancer Cells to Olaparib |
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