Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma
Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lin...
Gespeichert in:
| Veröffentlicht in: | Cell cycle (Georgetown, Tex.) Tex.), 2018-04, Vol.17 (8), p.997-1006 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1006 |
|---|---|
| container_issue | 8 |
| container_start_page | 997 |
| container_title | Cell cycle (Georgetown, Tex.) |
| container_volume | 17 |
| creator | Zhou, Pingting Li, Yanyan Li, Bo Zhang, Meichao Xu, Ci Liu, Furao Bian, Lei Liu, Yuanhua Yao, Yuan Li, Dong |
| description | Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lines-143B and U2OS. We showed that celecoxib inhibits OS cell growth, causes G0/G1-phase arrest, modulates apoptosis and autophagy and reduces migration in OS cells. In addition, the results of fluorescent mitochondrial probe JC-1 test indicated that the mitochondrial pathway mediates celecoxib-induced apoptosis. Significantly, the autophagy inhibitor CQ combined with celecoxib causes greater cell proliferation inhibition and apoptosis. Pharmacologic inhibition of autophagy with another potent autophagy inhibitor SAR405 also enhances celecoxib-mediated suppression of cell viability. These results were confirmed with shRNAs targeting the autophagy-related gene Atg5. In OS tumor xenografts in vivo, celecoxib also presents antitumor activity. Taken together, our results shed light on the function and mechanism of antitumor action of celecoxib for treatment of OS patients. |
| doi_str_mv | 10.1080/15384101.2018.1467677 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2052806619</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2052806619</sourcerecordid><originalsourceid>FETCH-LOGICAL-c468t-c585a68f8742725ce9238f77db6adaf682ea17568175ef94a639847655b9bc513</originalsourceid><addsrcrecordid>eNp9kUtP3DAUha2qqAy0P6Eoy24y2E782qCOEI-RRmIDa-vGcRhXiR3spDD_nkQzINiwsS3d755zfQ9CvwleEizxOWGFLAkmS4qJXJKSCy7EN7QgjJG8xJh9n9-FzGfoGJ2k9A9jKoUiP9AxVVKWWJEFWq_GIfRbeNxlzm9d5QYXfGb9FryxKTO2tSa8uCp3vh6NrTPoQz-E5NLEZyENNiSIJnTwEx010Cb763Cfoofrq_vL23xzd7O-XG1yU3I55IZJBlw2UpRUUGasooVshKgrDjU0XFILRDAup8M2qgReKFkKzlilKsNIcYou9rr9WHW2NtYPEVrdR9dB3OkATn-ueLfVj-G_5gQXXKlJ4M9BIIan0aZBdy5NH23B2zAmTTGjEnNOZpTtURNDStE27zYE6zkG_RaDnmPQhximvrOPM753ve19Av7uAeebEDt4DrGt9QC7NsQmTrt3SRdfe7wCOPWYjQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2052806619</pqid></control><display><type>article</type><title>Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Zhou, Pingting ; Li, Yanyan ; Li, Bo ; Zhang, Meichao ; Xu, Ci ; Liu, Furao ; Bian, Lei ; Liu, Yuanhua ; Yao, Yuan ; Li, Dong</creator><creatorcontrib>Zhou, Pingting ; Li, Yanyan ; Li, Bo ; Zhang, Meichao ; Xu, Ci ; Liu, Furao ; Bian, Lei ; Liu, Yuanhua ; Yao, Yuan ; Li, Dong</creatorcontrib><description>Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lines-143B and U2OS. We showed that celecoxib inhibits OS cell growth, causes G0/G1-phase arrest, modulates apoptosis and autophagy and reduces migration in OS cells. In addition, the results of fluorescent mitochondrial probe JC-1 test indicated that the mitochondrial pathway mediates celecoxib-induced apoptosis. Significantly, the autophagy inhibitor CQ combined with celecoxib causes greater cell proliferation inhibition and apoptosis. Pharmacologic inhibition of autophagy with another potent autophagy inhibitor SAR405 also enhances celecoxib-mediated suppression of cell viability. These results were confirmed with shRNAs targeting the autophagy-related gene Atg5. In OS tumor xenografts in vivo, celecoxib also presents antitumor activity. Taken together, our results shed light on the function and mechanism of antitumor action of celecoxib for treatment of OS patients.</description><identifier>ISSN: 1538-4101</identifier><identifier>ISSN: 1551-4005</identifier><identifier>EISSN: 1551-4005</identifier><identifier>DOI: 10.1080/15384101.2018.1467677</identifier><identifier>PMID: 29884091</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; apoptosis ; Apoptosis - drug effects ; autophagy ; Autophagy - drug effects ; Autophagy-Related Protein 5 - metabolism ; Carcinogenesis - drug effects ; Carcinogenesis - pathology ; Celecoxib ; Celecoxib - pharmacology ; Cell Cycle Checkpoints - drug effects ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Humans ; Mice, Inbred BALB C ; Mice, Nude ; osteosarcoma ; Osteosarcoma - pathology ; Research Paper ; Xenograft Model Antitumor Assays</subject><ispartof>Cell cycle (Georgetown, Tex.), 2018-04, Vol.17 (8), p.997-1006</ispartof><rights>2018 Informa UK Limited, trading as Taylor & Francis Group 2018</rights><rights>2018 Informa UK Limited, trading as Taylor & Francis Group 2018 Informa UK Limited, trading as Taylor & Francis Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-c585a68f8742725ce9238f77db6adaf682ea17568175ef94a639847655b9bc513</citedby><cites>FETCH-LOGICAL-c468t-c585a68f8742725ce9238f77db6adaf682ea17568175ef94a639847655b9bc513</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/PMC6103699/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6103699/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29884091$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Pingting</creatorcontrib><creatorcontrib>Li, Yanyan</creatorcontrib><creatorcontrib>Li, Bo</creatorcontrib><creatorcontrib>Zhang, Meichao</creatorcontrib><creatorcontrib>Xu, Ci</creatorcontrib><creatorcontrib>Liu, Furao</creatorcontrib><creatorcontrib>Bian, Lei</creatorcontrib><creatorcontrib>Liu, Yuanhua</creatorcontrib><creatorcontrib>Yao, Yuan</creatorcontrib><creatorcontrib>Li, Dong</creatorcontrib><title>Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma</title><title>Cell cycle (Georgetown, Tex.)</title><addtitle>Cell Cycle</addtitle><description>Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lines-143B and U2OS. We showed that celecoxib inhibits OS cell growth, causes G0/G1-phase arrest, modulates apoptosis and autophagy and reduces migration in OS cells. In addition, the results of fluorescent mitochondrial probe JC-1 test indicated that the mitochondrial pathway mediates celecoxib-induced apoptosis. Significantly, the autophagy inhibitor CQ combined with celecoxib causes greater cell proliferation inhibition and apoptosis. Pharmacologic inhibition of autophagy with another potent autophagy inhibitor SAR405 also enhances celecoxib-mediated suppression of cell viability. These results were confirmed with shRNAs targeting the autophagy-related gene Atg5. In OS tumor xenografts in vivo, celecoxib also presents antitumor activity. Taken together, our results shed light on the function and mechanism of antitumor action of celecoxib for treatment of OS patients.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>autophagy</subject><subject>Autophagy - drug effects</subject><subject>Autophagy-Related Protein 5 - metabolism</subject><subject>Carcinogenesis - drug effects</subject><subject>Carcinogenesis - pathology</subject><subject>Celecoxib</subject><subject>Celecoxib - pharmacology</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Humans</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>osteosarcoma</subject><subject>Osteosarcoma - pathology</subject><subject>Research Paper</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1538-4101</issn><issn>1551-4005</issn><issn>1551-4005</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUtP3DAUha2qqAy0P6Eoy24y2E782qCOEI-RRmIDa-vGcRhXiR3spDD_nkQzINiwsS3d755zfQ9CvwleEizxOWGFLAkmS4qJXJKSCy7EN7QgjJG8xJh9n9-FzGfoGJ2k9A9jKoUiP9AxVVKWWJEFWq_GIfRbeNxlzm9d5QYXfGb9FryxKTO2tSa8uCp3vh6NrTPoQz-E5NLEZyENNiSIJnTwEx010Cb763Cfoofrq_vL23xzd7O-XG1yU3I55IZJBlw2UpRUUGasooVshKgrDjU0XFILRDAup8M2qgReKFkKzlilKsNIcYou9rr9WHW2NtYPEVrdR9dB3OkATn-ueLfVj-G_5gQXXKlJ4M9BIIan0aZBdy5NH23B2zAmTTGjEnNOZpTtURNDStE27zYE6zkG_RaDnmPQhximvrOPM753ve19Av7uAeebEDt4DrGt9QC7NsQmTrt3SRdfe7wCOPWYjQ</recordid><startdate>20180418</startdate><enddate>20180418</enddate><creator>Zhou, Pingting</creator><creator>Li, Yanyan</creator><creator>Li, Bo</creator><creator>Zhang, Meichao</creator><creator>Xu, Ci</creator><creator>Liu, Furao</creator><creator>Bian, Lei</creator><creator>Liu, Yuanhua</creator><creator>Yao, Yuan</creator><creator>Li, Dong</creator><general>Taylor & Francis</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>20180418</creationdate><title>Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma</title><author>Zhou, Pingting ; Li, Yanyan ; Li, Bo ; Zhang, Meichao ; Xu, Ci ; Liu, Furao ; Bian, Lei ; Liu, Yuanhua ; Yao, Yuan ; Li, Dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-c585a68f8742725ce9238f77db6adaf682ea17568175ef94a639847655b9bc513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>autophagy</topic><topic>Autophagy - drug effects</topic><topic>Autophagy-Related Protein 5 - metabolism</topic><topic>Carcinogenesis - drug effects</topic><topic>Carcinogenesis - pathology</topic><topic>Celecoxib</topic><topic>Celecoxib - pharmacology</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Humans</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>osteosarcoma</topic><topic>Osteosarcoma - pathology</topic><topic>Research Paper</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Pingting</creatorcontrib><creatorcontrib>Li, Yanyan</creatorcontrib><creatorcontrib>Li, Bo</creatorcontrib><creatorcontrib>Zhang, Meichao</creatorcontrib><creatorcontrib>Xu, Ci</creatorcontrib><creatorcontrib>Liu, Furao</creatorcontrib><creatorcontrib>Bian, Lei</creatorcontrib><creatorcontrib>Liu, Yuanhua</creatorcontrib><creatorcontrib>Yao, Yuan</creatorcontrib><creatorcontrib>Li, Dong</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>Cell cycle (Georgetown, Tex.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Pingting</au><au>Li, Yanyan</au><au>Li, Bo</au><au>Zhang, Meichao</au><au>Xu, Ci</au><au>Liu, Furao</au><au>Bian, Lei</au><au>Liu, Yuanhua</au><au>Yao, Yuan</au><au>Li, Dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma</atitle><jtitle>Cell cycle (Georgetown, Tex.)</jtitle><addtitle>Cell Cycle</addtitle><date>2018-04-18</date><risdate>2018</risdate><volume>17</volume><issue>8</issue><spage>997</spage><epage>1006</epage><pages>997-1006</pages><issn>1538-4101</issn><issn>1551-4005</issn><eissn>1551-4005</eissn><abstract>Osteosarcoma (OS) is the most prevalent bone malignancy in childhood and adolescence, with highly aggressive and early systemic metastases. Here, we reported that celecoxib, a selective COX-2 inhibitor in the NSAID class, exhibits strong antitumor activity in dose dependent manner in two OS cell lines-143B and U2OS. We showed that celecoxib inhibits OS cell growth, causes G0/G1-phase arrest, modulates apoptosis and autophagy and reduces migration in OS cells. In addition, the results of fluorescent mitochondrial probe JC-1 test indicated that the mitochondrial pathway mediates celecoxib-induced apoptosis. Significantly, the autophagy inhibitor CQ combined with celecoxib causes greater cell proliferation inhibition and apoptosis. Pharmacologic inhibition of autophagy with another potent autophagy inhibitor SAR405 also enhances celecoxib-mediated suppression of cell viability. These results were confirmed with shRNAs targeting the autophagy-related gene Atg5. In OS tumor xenografts in vivo, celecoxib also presents antitumor activity. Taken together, our results shed light on the function and mechanism of antitumor action of celecoxib for treatment of OS patients.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>29884091</pmid><doi>10.1080/15384101.2018.1467677</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1538-4101 |
| ispartof | Cell cycle (Georgetown, Tex.), 2018-04, Vol.17 (8), p.997-1006 |
| issn | 1538-4101 1551-4005 1551-4005 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2052806619 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Animals Antineoplastic Agents - pharmacology apoptosis Apoptosis - drug effects autophagy Autophagy - drug effects Autophagy-Related Protein 5 - metabolism Carcinogenesis - drug effects Carcinogenesis - pathology Celecoxib Celecoxib - pharmacology Cell Cycle Checkpoints - drug effects Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Humans Mice, Inbred BALB C Mice, Nude osteosarcoma Osteosarcoma - pathology Research Paper Xenograft Model Antitumor Assays |
| title | Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T11%3A40%3A44IST&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=Autophagy%20inhibition%20enhances%20celecoxib-induced%20apoptosis%20in%20osteosarcoma&rft.jtitle=Cell%20cycle%20(Georgetown,%20Tex.)&rft.au=Zhou,%20Pingting&rft.date=2018-04-18&rft.volume=17&rft.issue=8&rft.spage=997&rft.epage=1006&rft.pages=997-1006&rft.issn=1538-4101&rft.eissn=1551-4005&rft_id=info:doi/10.1080/15384101.2018.1467677&rft_dat=%3Cproquest_pubme%3E2052806619%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=2052806619&rft_id=info:pmid/29884091&rfr_iscdi=true |