Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer
Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical...
Gespeichert in:
| Veröffentlicht in: | Oncotarget 2016-09, Vol.7 (36), p.58038-58050 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 58050 |
|---|---|
| container_issue | 36 |
| container_start_page | 58038 |
| container_title | Oncotarget |
| container_volume | 7 |
| creator | Liu, Bing Huang, XinPing Hu, YunLong Chen, TingTing Peng, BoYa Gao, NingNing Jin, ZhenChao Jia, TieLiu Zhang, Na Wang, ZhuLin Jin, GuangYi |
| description | Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer. |
| doi_str_mv | 10.18632/oncotarget.10846 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5295410</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1826741523</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-ea553c9623e263160975e2ec09310343030ea88328e2660bd2847b02a4d41ed73</originalsourceid><addsrcrecordid>eNpVUctO3DAUtVARoCkfwKbyks1Qv5I4m0oVAloJqRu6thznZuI2sdNrz6D5Bn4a8yild3OPdM59HkLOOLvgupbicwwuZosbyBecaVUfkBPeqnYtqkp-eIePyWlKv1iJSjVatEfkWDRKN1zoE_JwlUfrcB-8o9b5nvp5wbiDRPMI1Ibs83aOSGEYwOVE40A9IuwAk-8moLD4HnC2E91gvM8jHazLRY_gYHkCeY8x-QD0tw82AfVh9J0vTCqQdgg2ZepscIAfyeFgpwSnr3lFfl5f3V1-W9_-uPl--fV27WRV5zXYcpRrayFB1JLXrG0qEOBYKzmTSjLJwGothS58zbpeaNV0TFjVKw59I1fky0vfZdvN0DsIGe1kFvSzxb2J1pv_meBHs4k7U4m2UmXGipy_NsD4Zwspm9knB9NkA8RtMlyLulG8ErJI-YvUlTckhOFtDGfm2Ufzz0fz7GOp-fR-v7eKv67JR8l_oAg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1826741523</pqid></control><display><type>article</type><title>Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free E- Journals</source><source>PubMed Central Open Access</source><creator>Liu, Bing ; Huang, XinPing ; Hu, YunLong ; Chen, TingTing ; Peng, BoYa ; Gao, NingNing ; Jin, ZhenChao ; Jia, TieLiu ; Zhang, Na ; Wang, ZhuLin ; Jin, GuangYi</creator><creatorcontrib>Liu, Bing ; Huang, XinPing ; Hu, YunLong ; Chen, TingTing ; Peng, BoYa ; Gao, NingNing ; Jin, ZhenChao ; Jia, TieLiu ; Zhang, Na ; Wang, ZhuLin ; Jin, GuangYi</creatorcontrib><description>Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.10846</identifier><identifier>PMID: 27487128</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Apoptosis - drug effects ; Breast - pathology ; Breast Neoplasms - drug therapy ; Breast Neoplasms - pathology ; Cell Cycle Checkpoints - drug effects ; Cell Proliferation - drug effects ; Drug Resistance, Neoplasm - drug effects ; Drug Synergism ; Ethacrynic Acid - pharmacology ; Ethacrynic Acid - therapeutic use ; Female ; Humans ; MAP Kinase Signaling System - drug effects ; MCF-7 Cells ; Mice, Inbred BALB C ; Protein Kinase Inhibitors - pharmacology ; Protein Kinase Inhibitors - therapeutic use ; Quinazolines - pharmacology ; Quinazolines - therapeutic use ; Quinolines - pharmacology ; Quinolines - therapeutic use ; Receptor, Epidermal Growth Factor - antagonists & inhibitors ; Research Paper ; Wnt Signaling Pathway - drug effects ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2016-09, Vol.7 (36), p.58038-58050</ispartof><rights>Copyright: © 2016 Liu et al. 2016</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-ea553c9623e263160975e2ec09310343030ea88328e2660bd2847b02a4d41ed73</citedby><cites>FETCH-LOGICAL-c356t-ea553c9623e263160975e2ec09310343030ea88328e2660bd2847b02a4d41ed73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295410/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295410/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27487128$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Bing</creatorcontrib><creatorcontrib>Huang, XinPing</creatorcontrib><creatorcontrib>Hu, YunLong</creatorcontrib><creatorcontrib>Chen, TingTing</creatorcontrib><creatorcontrib>Peng, BoYa</creatorcontrib><creatorcontrib>Gao, NingNing</creatorcontrib><creatorcontrib>Jin, ZhenChao</creatorcontrib><creatorcontrib>Jia, TieLiu</creatorcontrib><creatorcontrib>Zhang, Na</creatorcontrib><creatorcontrib>Wang, ZhuLin</creatorcontrib><creatorcontrib>Jin, GuangYi</creatorcontrib><title>Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Breast - pathology</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Drug Synergism</subject><subject>Ethacrynic Acid - pharmacology</subject><subject>Ethacrynic Acid - therapeutic use</subject><subject>Female</subject><subject>Humans</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>MCF-7 Cells</subject><subject>Mice, Inbred BALB C</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Kinase Inhibitors - therapeutic use</subject><subject>Quinazolines - pharmacology</subject><subject>Quinazolines - therapeutic use</subject><subject>Quinolines - pharmacology</subject><subject>Quinolines - therapeutic use</subject><subject>Receptor, Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Research Paper</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVUctO3DAUtVARoCkfwKbyks1Qv5I4m0oVAloJqRu6thznZuI2sdNrz6D5Bn4a8yild3OPdM59HkLOOLvgupbicwwuZosbyBecaVUfkBPeqnYtqkp-eIePyWlKv1iJSjVatEfkWDRKN1zoE_JwlUfrcB-8o9b5nvp5wbiDRPMI1Ibs83aOSGEYwOVE40A9IuwAk-8moLD4HnC2E91gvM8jHazLRY_gYHkCeY8x-QD0tw82AfVh9J0vTCqQdgg2ZepscIAfyeFgpwSnr3lFfl5f3V1-W9_-uPl--fV27WRV5zXYcpRrayFB1JLXrG0qEOBYKzmTSjLJwGothS58zbpeaNV0TFjVKw59I1fky0vfZdvN0DsIGe1kFvSzxb2J1pv_meBHs4k7U4m2UmXGipy_NsD4Zwspm9knB9NkA8RtMlyLulG8ErJI-YvUlTckhOFtDGfm2Ufzz0fz7GOp-fR-v7eKv67JR8l_oAg</recordid><startdate>20160906</startdate><enddate>20160906</enddate><creator>Liu, Bing</creator><creator>Huang, XinPing</creator><creator>Hu, YunLong</creator><creator>Chen, TingTing</creator><creator>Peng, BoYa</creator><creator>Gao, NingNing</creator><creator>Jin, ZhenChao</creator><creator>Jia, TieLiu</creator><creator>Zhang, Na</creator><creator>Wang, ZhuLin</creator><creator>Jin, GuangYi</creator><general>Impact Journals LLC</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>5PM</scope></search><sort><creationdate>20160906</creationdate><title>Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer</title><author>Liu, Bing ; Huang, XinPing ; Hu, YunLong ; Chen, TingTing ; Peng, BoYa ; Gao, NingNing ; Jin, ZhenChao ; Jia, TieLiu ; Zhang, Na ; Wang, ZhuLin ; Jin, GuangYi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-ea553c9623e263160975e2ec09310343030ea88328e2660bd2847b02a4d41ed73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>Breast - pathology</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Drug Synergism</topic><topic>Ethacrynic Acid - pharmacology</topic><topic>Ethacrynic Acid - therapeutic use</topic><topic>Female</topic><topic>Humans</topic><topic>MAP Kinase Signaling System - drug effects</topic><topic>MCF-7 Cells</topic><topic>Mice, Inbred BALB C</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein Kinase Inhibitors - therapeutic use</topic><topic>Quinazolines - pharmacology</topic><topic>Quinazolines - therapeutic use</topic><topic>Quinolines - pharmacology</topic><topic>Quinolines - therapeutic use</topic><topic>Receptor, Epidermal Growth Factor - antagonists & inhibitors</topic><topic>Research Paper</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Liu, Bing</creatorcontrib><creatorcontrib>Huang, XinPing</creatorcontrib><creatorcontrib>Hu, YunLong</creatorcontrib><creatorcontrib>Chen, TingTing</creatorcontrib><creatorcontrib>Peng, BoYa</creatorcontrib><creatorcontrib>Gao, NingNing</creatorcontrib><creatorcontrib>Jin, ZhenChao</creatorcontrib><creatorcontrib>Jia, TieLiu</creatorcontrib><creatorcontrib>Zhang, Na</creatorcontrib><creatorcontrib>Wang, ZhuLin</creatorcontrib><creatorcontrib>Jin, GuangYi</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>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Bing</au><au>Huang, XinPing</au><au>Hu, YunLong</au><au>Chen, TingTing</au><au>Peng, BoYa</au><au>Gao, NingNing</au><au>Jin, ZhenChao</au><au>Jia, TieLiu</au><au>Zhang, Na</au><au>Wang, ZhuLin</au><au>Jin, GuangYi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2016-09-06</date><risdate>2016</risdate><volume>7</volume><issue>36</issue><spage>58038</spage><epage>58050</epage><pages>58038-58050</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Prolonged treatment of breast cancer with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) often results in acquired resistance and a narrow therapeutic index. One strategy to improve the therapeutic effects of EGFR TKIs is to combine them with drugs used for other clinical indications. Ethacrynic acid (EA) is an FDA approved drug that may have antitumor effects and may enhance the cytotoxicity of chemotherapeutic agents by binding to glutathione and inhibiting WNT signaling. While the α,β-unsaturated-keto structure of EA is similar to that of irreversible TKIs, the mechanism of action of EA when combined with irreversible EGFR TKIs in breast cancer remains unknown. We therefore investigated the combination of irreversible EGFR TKIs and EA. We found that irreversible EGFR TKIs and EA synergistically inhibit breast cancer both in vitro and in vivo. The combination of EGFR TKIs and EA induces necrosis and cell cycle arrest and represses WNT/β-catenin signaling as well as MAPK-ERK1/2 signaling. We conclude that EA synergistically enhances the antitumor effects of irreversible EGFR TKIs in breast cancer.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>27487128</pmid><doi>10.18632/oncotarget.10846</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1949-2553 |
| ispartof | Oncotarget, 2016-09, Vol.7 (36), p.58038-58050 |
| issn | 1949-2553 1949-2553 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5295410 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free E- Journals; PubMed Central Open Access |
| subjects | Animals Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Antineoplastic Combined Chemotherapy Protocols - pharmacology Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis - drug effects Breast - pathology Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Cycle Checkpoints - drug effects Cell Proliferation - drug effects Drug Resistance, Neoplasm - drug effects Drug Synergism Ethacrynic Acid - pharmacology Ethacrynic Acid - therapeutic use Female Humans MAP Kinase Signaling System - drug effects MCF-7 Cells Mice, Inbred BALB C Protein Kinase Inhibitors - pharmacology Protein Kinase Inhibitors - therapeutic use Quinazolines - pharmacology Quinazolines - therapeutic use Quinolines - pharmacology Quinolines - therapeutic use Receptor, Epidermal Growth Factor - antagonists & inhibitors Research Paper Wnt Signaling Pathway - drug effects Xenograft Model Antitumor Assays |
| title | Ethacrynic acid improves the antitumor effects of irreversible epidermal growth factor receptor tyrosine kinase inhibitors in breast cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T20%3A40%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ethacrynic%20acid%20improves%20the%20antitumor%20effects%20of%20irreversible%20epidermal%20growth%20factor%20receptor%20tyrosine%20kinase%20inhibitors%20in%20breast%20cancer&rft.jtitle=Oncotarget&rft.au=Liu,%20Bing&rft.date=2016-09-06&rft.volume=7&rft.issue=36&rft.spage=58038&rft.epage=58050&rft.pages=58038-58050&rft.issn=1949-2553&rft.eissn=1949-2553&rft_id=info:doi/10.18632/oncotarget.10846&rft_dat=%3Cproquest_pubme%3E1826741523%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1826741523&rft_id=info:pmid/27487128&rfr_iscdi=true |