Quercetin attenuates the cardiotoxicity of doxorubicin–cyclophosphamide regimen and potentiates its chemotherapeutic effect against triple‐negative breast cancer
Doxorubicin combined with cyclophosphamide (AC) is the most commonly used regimen for triple‐negative breast cancer (TNBC) chemotherapy; however, its clinical application is severely limited by its serious adverse effect on cardiomyocytes. The cardiotoxicity of AC is mainly the result of oxidative s...
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| Veröffentlicht in: | Phytotherapy research 2022-01, Vol.36 (1), p.551-561 |
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| creator | Zhang, Puwei Zhang, Jianing Zhao, Lin Li, Shizheng Li, Kun |
| description | Doxorubicin combined with cyclophosphamide (AC) is the most commonly used regimen for triple‐negative breast cancer (TNBC) chemotherapy; however, its clinical application is severely limited by its serious adverse effect on cardiomyocytes. The cardiotoxicity of AC is mainly the result of oxidative stress caused by the imbalance between reactive oxygen species (ROS) and antioxidants, and it also involves multiple signaling pathways. Quercetin (Que) has been proven to possess strong antioxidant activity, and therefore we investigated whether it had potential protective effect against AC‐induced cardiotoxicity. Meanwhile, we also evaluated its effect on the antitumor activity of AC. Our in vitro studies showed that Que could attenuate AC‐induced cardiotoxicity by inhibiting ROS accumulation and activating ERK1/2 pathway in cardiomyocytes, but interestingly, Que could enhance the antitumor activity of AC by inhibiting ROS accumulation and ERK1/2 pathway in TNBC cells. In addition, our in vivo studies further confirmed that Que could enhance the chemotherapeutic effect of AC against TNBC while it reduced the injury of cardiotoxicity induced by AC. Therefore, Que could be used as a novel agent for the treatment of cardiotoxicity induced by AC regimen in TNBC chemotherapy. |
| doi_str_mv | 10.1002/ptr.7342 |
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The cardiotoxicity of AC is mainly the result of oxidative stress caused by the imbalance between reactive oxygen species (ROS) and antioxidants, and it also involves multiple signaling pathways. Quercetin (Que) has been proven to possess strong antioxidant activity, and therefore we investigated whether it had potential protective effect against AC‐induced cardiotoxicity. Meanwhile, we also evaluated its effect on the antitumor activity of AC. Our in vitro studies showed that Que could attenuate AC‐induced cardiotoxicity by inhibiting ROS accumulation and activating ERK1/2 pathway in cardiomyocytes, but interestingly, Que could enhance the antitumor activity of AC by inhibiting ROS accumulation and ERK1/2 pathway in TNBC cells. In addition, our in vivo studies further confirmed that Que could enhance the chemotherapeutic effect of AC against TNBC while it reduced the injury of cardiotoxicity induced by AC. Therefore, Que could be used as a novel agent for the treatment of cardiotoxicity induced by AC regimen in TNBC chemotherapy.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.7342</identifier><identifier>PMID: 34951067</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Accumulation ; Anticancer properties ; Antioxidants ; Antitumor activity ; Breast cancer ; Cardiomyocytes ; Cardiotoxicity ; Cardiotoxicity - drug therapy ; Chemotherapy ; Cyclophosphamide ; Cyclophosphamide - adverse effects ; Doxorubicin ; Doxorubicin - adverse effects ; ERK1/2 pathway ; Humans ; In vivo methods and tests ; Injury prevention ; Oxidative stress ; Quercetin ; Quercetin - pharmacology ; Reactive oxygen species ; ROS ; Triple Negative Breast Neoplasms - drug therapy ; triple‐negative breast cancer</subject><ispartof>Phytotherapy research, 2022-01, Vol.36 (1), p.551-561</ispartof><rights>2021 John Wiley & Sons Ltd.</rights><rights>2022 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3492-8336ace103d5c7138133d00ceea1eb7f543d33856abdda997547134a5ecebc903</citedby><cites>FETCH-LOGICAL-c3492-8336ace103d5c7138133d00ceea1eb7f543d33856abdda997547134a5ecebc903</cites><orcidid>0000-0002-8668-9405</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fptr.7342$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.7342$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34951067$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Puwei</creatorcontrib><creatorcontrib>Zhang, Jianing</creatorcontrib><creatorcontrib>Zhao, Lin</creatorcontrib><creatorcontrib>Li, Shizheng</creatorcontrib><creatorcontrib>Li, Kun</creatorcontrib><title>Quercetin attenuates the cardiotoxicity of doxorubicin–cyclophosphamide regimen and potentiates its chemotherapeutic effect against triple‐negative breast cancer</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>Doxorubicin combined with cyclophosphamide (AC) is the most commonly used regimen for triple‐negative breast cancer (TNBC) chemotherapy; however, its clinical application is severely limited by its serious adverse effect on cardiomyocytes. The cardiotoxicity of AC is mainly the result of oxidative stress caused by the imbalance between reactive oxygen species (ROS) and antioxidants, and it also involves multiple signaling pathways. Quercetin (Que) has been proven to possess strong antioxidant activity, and therefore we investigated whether it had potential protective effect against AC‐induced cardiotoxicity. Meanwhile, we also evaluated its effect on the antitumor activity of AC. Our in vitro studies showed that Que could attenuate AC‐induced cardiotoxicity by inhibiting ROS accumulation and activating ERK1/2 pathway in cardiomyocytes, but interestingly, Que could enhance the antitumor activity of AC by inhibiting ROS accumulation and ERK1/2 pathway in TNBC cells. In addition, our in vivo studies further confirmed that Que could enhance the chemotherapeutic effect of AC against TNBC while it reduced the injury of cardiotoxicity induced by AC. Therefore, Que could be used as a novel agent for the treatment of cardiotoxicity induced by AC regimen in TNBC chemotherapy.</description><subject>Accumulation</subject><subject>Anticancer properties</subject><subject>Antioxidants</subject><subject>Antitumor activity</subject><subject>Breast cancer</subject><subject>Cardiomyocytes</subject><subject>Cardiotoxicity</subject><subject>Cardiotoxicity - drug therapy</subject><subject>Chemotherapy</subject><subject>Cyclophosphamide</subject><subject>Cyclophosphamide - adverse effects</subject><subject>Doxorubicin</subject><subject>Doxorubicin - adverse effects</subject><subject>ERK1/2 pathway</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Injury prevention</subject><subject>Oxidative stress</subject><subject>Quercetin</subject><subject>Quercetin - pharmacology</subject><subject>Reactive oxygen species</subject><subject>ROS</subject><subject>Triple Negative Breast Neoplasms - drug therapy</subject><subject>triple‐negative breast cancer</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kdFqFTEQhoNY7LEKPoEEvPFma7LJnj17KcWqUNCWCt4ts5PZc1J2kzXJ2p67PoLgM_hifRJz2mpB8GoY_o-PGX7GXkhxKIUo30wpHNZKl4_YQoqmKWRVq8dsIZpKFlquvu6zpzFeCCGaUugnbF_pnIhlvWC_TmcKSMk6DimRmyFR5GlDHCEY65O_smjTlvueG3_lw9zl3d1c_8QtDn7a-DhtYLSGeKC1HSl7nOGTz65kb2U2RY4bGn22BphoThY59T1h4rAG62LiKdhpoJvrH47WkOx34l0gyAGCQwrP2F4PQ6Tn9_OAfTl-d370oTj59P7j0duTAvNHZbFSaglIUihTYS3VSiplhEAikNTVfaWVUWpVLaEzBpqmrnSmNFSE1GEj1AF7feedgv82U0ztaCPSMIAjP8e2XEpdKiH0Dn31D3rh5-DydZkqpZa6UtWDEIOPMVDfTsGOELatFO2uujZX1-6qy-jLe-HcjWT-gn-6ykBxB1zagbb_FbWfz89uhb8B4VCpkg</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Zhang, Puwei</creator><creator>Zhang, Jianing</creator><creator>Zhao, Lin</creator><creator>Li, Shizheng</creator><creator>Li, Kun</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</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>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-8668-9405</orcidid></search><sort><creationdate>202201</creationdate><title>Quercetin attenuates the cardiotoxicity of doxorubicin–cyclophosphamide regimen and potentiates its chemotherapeutic effect against triple‐negative breast cancer</title><author>Zhang, Puwei ; Zhang, Jianing ; Zhao, Lin ; Li, Shizheng ; Li, Kun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3492-8336ace103d5c7138133d00ceea1eb7f543d33856abdda997547134a5ecebc903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Accumulation</topic><topic>Anticancer properties</topic><topic>Antioxidants</topic><topic>Antitumor activity</topic><topic>Breast cancer</topic><topic>Cardiomyocytes</topic><topic>Cardiotoxicity</topic><topic>Cardiotoxicity - drug therapy</topic><topic>Chemotherapy</topic><topic>Cyclophosphamide</topic><topic>Cyclophosphamide - adverse effects</topic><topic>Doxorubicin</topic><topic>Doxorubicin - adverse effects</topic><topic>ERK1/2 pathway</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>Injury prevention</topic><topic>Oxidative stress</topic><topic>Quercetin</topic><topic>Quercetin - pharmacology</topic><topic>Reactive oxygen species</topic><topic>ROS</topic><topic>Triple Negative Breast Neoplasms - drug therapy</topic><topic>triple‐negative breast cancer</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Puwei</creatorcontrib><creatorcontrib>Zhang, Jianing</creatorcontrib><creatorcontrib>Zhao, Lin</creatorcontrib><creatorcontrib>Li, Shizheng</creatorcontrib><creatorcontrib>Li, Kun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Puwei</au><au>Zhang, Jianing</au><au>Zhao, Lin</au><au>Li, Shizheng</au><au>Li, Kun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quercetin attenuates the cardiotoxicity of doxorubicin–cyclophosphamide regimen and potentiates its chemotherapeutic effect against triple‐negative breast cancer</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2022-01</date><risdate>2022</risdate><volume>36</volume><issue>1</issue><spage>551</spage><epage>561</epage><pages>551-561</pages><issn>0951-418X</issn><eissn>1099-1573</eissn><abstract>Doxorubicin combined with cyclophosphamide (AC) is the most commonly used regimen for triple‐negative breast cancer (TNBC) chemotherapy; however, its clinical application is severely limited by its serious adverse effect on cardiomyocytes. The cardiotoxicity of AC is mainly the result of oxidative stress caused by the imbalance between reactive oxygen species (ROS) and antioxidants, and it also involves multiple signaling pathways. Quercetin (Que) has been proven to possess strong antioxidant activity, and therefore we investigated whether it had potential protective effect against AC‐induced cardiotoxicity. Meanwhile, we also evaluated its effect on the antitumor activity of AC. Our in vitro studies showed that Que could attenuate AC‐induced cardiotoxicity by inhibiting ROS accumulation and activating ERK1/2 pathway in cardiomyocytes, but interestingly, Que could enhance the antitumor activity of AC by inhibiting ROS accumulation and ERK1/2 pathway in TNBC cells. In addition, our in vivo studies further confirmed that Que could enhance the chemotherapeutic effect of AC against TNBC while it reduced the injury of cardiotoxicity induced by AC. Therefore, Que could be used as a novel agent for the treatment of cardiotoxicity induced by AC regimen in TNBC chemotherapy.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>34951067</pmid><doi>10.1002/ptr.7342</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8668-9405</orcidid></addata></record> |
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| subjects | Accumulation Anticancer properties Antioxidants Antitumor activity Breast cancer Cardiomyocytes Cardiotoxicity Cardiotoxicity - drug therapy Chemotherapy Cyclophosphamide Cyclophosphamide - adverse effects Doxorubicin Doxorubicin - adverse effects ERK1/2 pathway Humans In vivo methods and tests Injury prevention Oxidative stress Quercetin Quercetin - pharmacology Reactive oxygen species ROS Triple Negative Breast Neoplasms - drug therapy triple‐negative breast cancer |
| title | Quercetin attenuates the cardiotoxicity of doxorubicin–cyclophosphamide regimen and potentiates its chemotherapeutic effect against triple‐negative breast cancer |
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