Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3
Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti‐tumor, anti‐oxidant, anti‐viral, and he...
Gespeichert in:
| Veröffentlicht in: | Phytotherapy research 2023-03, Vol.37 (3), p.809-819 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 819 |
|---|---|
| container_issue | 3 |
| container_start_page | 809 |
| container_title | Phytotherapy research |
| container_volume | 37 |
| creator | Chen, Lin‐lin Xia, Liu‐yuan Zhang, Jun‐ping Wang, Yan Chen, Jian‐yu Guo, Cheng Xu, Wei‐heng |
| description | Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti‐tumor, anti‐oxidant, anti‐viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM‐induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING‐finger containing protein‐1 (MuRF1) and muscle atrophy Fbox protein (Atrogin‐1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia. |
| doi_str_mv | 10.1002/ptr.7676 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2743506459</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2743506459</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3496-20dbfdc3f0f52bf16e95bf4936b88802eed60c3278e721db2e5dd2bf82e645853</originalsourceid><addsrcrecordid>eNp10E9LwzAYx_Egis4p-Aqk4MVLNf-bHIc6FQaKm-CtpOlTl9m1M-nUvXujTgXB03P58OXhh9ABwScEY3q66PxJJjO5gXoEa50SkbFN1MNakJQT9bCDdkOYYYw1xXwb7TDJecaU6KHh2LinNphF27gmOU9MXcOLMx2ExJrGgo_HTuHNmaRYJaXzYLt6lbhm6grXueYxGU8GE7aHtipTB9hf3z66H15Mzq7S0c3l9dlglFrGtUwpLouqtKzClaBFRSRoUVRcM1kopTAFKCW2jGYKMkrKgoIoywgVBcmFEqyPjr-6C98-LyF0-dwFC3VtGmiXIacZZwJHqyM9-kNn7dI38buoFJGZkFz_Bq1vQ_BQ5Qvv5savcoLzj23zuG3-sW2kh-vgsphD-QO_x4wg_QKvrobVv6H8dnL3GXwH8vGBuw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2781675649</pqid></control><display><type>article</type><title>Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Chen, Lin‐lin ; Xia, Liu‐yuan ; Zhang, Jun‐ping ; Wang, Yan ; Chen, Jian‐yu ; Guo, Cheng ; Xu, Wei‐heng</creator><creatorcontrib>Chen, Lin‐lin ; Xia, Liu‐yuan ; Zhang, Jun‐ping ; Wang, Yan ; Chen, Jian‐yu ; Guo, Cheng ; Xu, Wei‐heng</creatorcontrib><description>Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti‐tumor, anti‐oxidant, anti‐viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM‐induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING‐finger containing protein‐1 (MuRF1) and muscle atrophy Fbox protein (Atrogin‐1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.7676</identifier><identifier>PMID: 36447385</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Atrophy ; Body weight ; Cachexia ; Cachexia - drug therapy ; Cachexia - metabolism ; Cachexia - pathology ; Cancer ; cancer cachexia ; Data storage ; Drug development ; E3 ubiquitin ligases ; Gastrocnemius muscle ; Humans ; In vivo methods and tests ; Metabolic disorders ; Metabolic syndrome ; muscle wasting ; Muscle, Skeletal ; Muscles ; Muscular Atrophy - drug therapy ; Myotubes ; Neoplasms - pathology ; Oxidants ; Oxidizing agents ; Phosphorylation ; Proteins ; Saikosaponin D ; Skeletal muscle ; Solid state devices ; STAT3 ; Stat3 protein ; STAT3 Transcription Factor - metabolism ; Tibialis anterior muscle ; Ubiquitin ; Ubiquitin-protein ligase</subject><ispartof>Phytotherapy research, 2023-03, Vol.37 (3), p.809-819</ispartof><rights>2022 John Wiley & Sons Ltd.</rights><rights>2023 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3496-20dbfdc3f0f52bf16e95bf4936b88802eed60c3278e721db2e5dd2bf82e645853</citedby><cites>FETCH-LOGICAL-c3496-20dbfdc3f0f52bf16e95bf4936b88802eed60c3278e721db2e5dd2bf82e645853</cites><orcidid>0000-0002-6778-6226 ; 0000-0003-1264-0761 ; 0000-0003-2578-6524</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.7676$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.7676$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36447385$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Lin‐lin</creatorcontrib><creatorcontrib>Xia, Liu‐yuan</creatorcontrib><creatorcontrib>Zhang, Jun‐ping</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Chen, Jian‐yu</creatorcontrib><creatorcontrib>Guo, Cheng</creatorcontrib><creatorcontrib>Xu, Wei‐heng</creatorcontrib><title>Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3</title><title>Phytotherapy research</title><addtitle>Phytother Res</addtitle><description>Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti‐tumor, anti‐oxidant, anti‐viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM‐induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING‐finger containing protein‐1 (MuRF1) and muscle atrophy Fbox protein (Atrogin‐1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia.</description><subject>Atrophy</subject><subject>Body weight</subject><subject>Cachexia</subject><subject>Cachexia - drug therapy</subject><subject>Cachexia - metabolism</subject><subject>Cachexia - pathology</subject><subject>Cancer</subject><subject>cancer cachexia</subject><subject>Data storage</subject><subject>Drug development</subject><subject>E3 ubiquitin ligases</subject><subject>Gastrocnemius muscle</subject><subject>Humans</subject><subject>In vivo methods and tests</subject><subject>Metabolic disorders</subject><subject>Metabolic syndrome</subject><subject>muscle wasting</subject><subject>Muscle, Skeletal</subject><subject>Muscles</subject><subject>Muscular Atrophy - drug therapy</subject><subject>Myotubes</subject><subject>Neoplasms - pathology</subject><subject>Oxidants</subject><subject>Oxidizing agents</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Saikosaponin D</subject><subject>Skeletal muscle</subject><subject>Solid state devices</subject><subject>STAT3</subject><subject>Stat3 protein</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Tibialis anterior muscle</subject><subject>Ubiquitin</subject><subject>Ubiquitin-protein ligase</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E9LwzAYx_Egis4p-Aqk4MVLNf-bHIc6FQaKm-CtpOlTl9m1M-nUvXujTgXB03P58OXhh9ABwScEY3q66PxJJjO5gXoEa50SkbFN1MNakJQT9bCDdkOYYYw1xXwb7TDJecaU6KHh2LinNphF27gmOU9MXcOLMx2ExJrGgo_HTuHNmaRYJaXzYLt6lbhm6grXueYxGU8GE7aHtipTB9hf3z66H15Mzq7S0c3l9dlglFrGtUwpLouqtKzClaBFRSRoUVRcM1kopTAFKCW2jGYKMkrKgoIoywgVBcmFEqyPjr-6C98-LyF0-dwFC3VtGmiXIacZZwJHqyM9-kNn7dI38buoFJGZkFz_Bq1vQ_BQ5Qvv5savcoLzj23zuG3-sW2kh-vgsphD-QO_x4wg_QKvrobVv6H8dnL3GXwH8vGBuw</recordid><startdate>202303</startdate><enddate>202303</enddate><creator>Chen, Lin‐lin</creator><creator>Xia, Liu‐yuan</creator><creator>Zhang, Jun‐ping</creator><creator>Wang, Yan</creator><creator>Chen, Jian‐yu</creator><creator>Guo, Cheng</creator><creator>Xu, Wei‐heng</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/0000-0002-6778-6226</orcidid><orcidid>https://orcid.org/0000-0003-1264-0761</orcidid><orcidid>https://orcid.org/0000-0003-2578-6524</orcidid></search><sort><creationdate>202303</creationdate><title>Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3</title><author>Chen, Lin‐lin ; Xia, Liu‐yuan ; Zhang, Jun‐ping ; Wang, Yan ; Chen, Jian‐yu ; Guo, Cheng ; Xu, Wei‐heng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3496-20dbfdc3f0f52bf16e95bf4936b88802eed60c3278e721db2e5dd2bf82e645853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Atrophy</topic><topic>Body weight</topic><topic>Cachexia</topic><topic>Cachexia - drug therapy</topic><topic>Cachexia - metabolism</topic><topic>Cachexia - pathology</topic><topic>Cancer</topic><topic>cancer cachexia</topic><topic>Data storage</topic><topic>Drug development</topic><topic>E3 ubiquitin ligases</topic><topic>Gastrocnemius muscle</topic><topic>Humans</topic><topic>In vivo methods and tests</topic><topic>Metabolic disorders</topic><topic>Metabolic syndrome</topic><topic>muscle wasting</topic><topic>Muscle, Skeletal</topic><topic>Muscles</topic><topic>Muscular Atrophy - drug therapy</topic><topic>Myotubes</topic><topic>Neoplasms - pathology</topic><topic>Oxidants</topic><topic>Oxidizing agents</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Saikosaponin D</topic><topic>Skeletal muscle</topic><topic>Solid state devices</topic><topic>STAT3</topic><topic>Stat3 protein</topic><topic>STAT3 Transcription Factor - metabolism</topic><topic>Tibialis anterior muscle</topic><topic>Ubiquitin</topic><topic>Ubiquitin-protein ligase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Lin‐lin</creatorcontrib><creatorcontrib>Xia, Liu‐yuan</creatorcontrib><creatorcontrib>Zhang, Jun‐ping</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Chen, Jian‐yu</creatorcontrib><creatorcontrib>Guo, Cheng</creatorcontrib><creatorcontrib>Xu, Wei‐heng</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>Chen, Lin‐lin</au><au>Xia, Liu‐yuan</au><au>Zhang, Jun‐ping</au><au>Wang, Yan</au><au>Chen, Jian‐yu</au><au>Guo, Cheng</au><au>Xu, Wei‐heng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3</atitle><jtitle>Phytotherapy research</jtitle><addtitle>Phytother Res</addtitle><date>2023-03</date><risdate>2023</risdate><volume>37</volume><issue>3</issue><spage>809</spage><epage>819</epage><pages>809-819</pages><issn>0951-418X</issn><eissn>1099-1573</eissn><abstract>Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti‐tumor, anti‐oxidant, anti‐viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM‐induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING‐finger containing protein‐1 (MuRF1) and muscle atrophy Fbox protein (Atrogin‐1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>36447385</pmid><doi>10.1002/ptr.7676</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-6778-6226</orcidid><orcidid>https://orcid.org/0000-0003-1264-0761</orcidid><orcidid>https://orcid.org/0000-0003-2578-6524</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0951-418X |
| ispartof | Phytotherapy research, 2023-03, Vol.37 (3), p.809-819 |
| issn | 0951-418X 1099-1573 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2743506459 |
| source | MEDLINE; Access via Wiley Online Library |
| subjects | Atrophy Body weight Cachexia Cachexia - drug therapy Cachexia - metabolism Cachexia - pathology Cancer cancer cachexia Data storage Drug development E3 ubiquitin ligases Gastrocnemius muscle Humans In vivo methods and tests Metabolic disorders Metabolic syndrome muscle wasting Muscle, Skeletal Muscles Muscular Atrophy - drug therapy Myotubes Neoplasms - pathology Oxidants Oxidizing agents Phosphorylation Proteins Saikosaponin D Skeletal muscle Solid state devices STAT3 Stat3 protein STAT3 Transcription Factor - metabolism Tibialis anterior muscle Ubiquitin Ubiquitin-protein ligase |
| title | Saikosaponin D alleviates cancer cachexia by directly inhibiting STAT3 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T11%3A00%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Saikosaponin%20D%20alleviates%20cancer%20cachexia%20by%20directly%20inhibiting%20STAT3&rft.jtitle=Phytotherapy%20research&rft.au=Chen,%20Lin%E2%80%90lin&rft.date=2023-03&rft.volume=37&rft.issue=3&rft.spage=809&rft.epage=819&rft.pages=809-819&rft.issn=0951-418X&rft.eissn=1099-1573&rft_id=info:doi/10.1002/ptr.7676&rft_dat=%3Cproquest_cross%3E2743506459%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2781675649&rft_id=info:pmid/36447385&rfr_iscdi=true |