Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells
Golgi reassembly and stacking protein 65 (GRASP65), which has been involved in cancer progression, is associated with tumor growth and cell apoptosis. Dihydromyricetin (DHM) has demonstrated antitumor activity in different types of human cancers. However, the pharmacological effects of DHM on ovaria...
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| description | Golgi reassembly and stacking protein 65 (GRASP65), which has been involved in cancer progression, is associated with tumor growth and cell apoptosis. Dihydromyricetin (DHM) has demonstrated antitumor activity in different types of human cancers. However, the pharmacological effects of DHM on ovarian cancer (OC) and the molecular mechanisms that underlie these effects are largely unknown. The present study showed that DHM reduced cell migration and invasion in a concentration- and time-dependent manner and induced cell apoptosis primarily through upregulation of Cleaved-caspase-3 and the Bax/Bcl-2 ratio in OCs. To further clarify the cancer therapeutic target, we assessed the effect of DHM on the expression of GRASP65, which is overexpressed in human ovarian cancer tissues. DHM activated caspase-3 and decreased GRASP65 expression to promote cell apoptosis, implying that downregulation of GRASP65 was related to DHM-induced cell apoptosis. Additionally, the knockdown of GRASP65 by siRNA resulted in increased apoptosis after DHM treatment, while western blot and flow cytometry analysis demonstrated that overexpression of GRASP65 attenuated DHM-mediated apoptosis. In addition, the JNK/ERK pathway may be involved in DHM-mediated caspase-3 activation and GRASP65 downregulation. Taken together, these findings provide novel evidence of the anti-cancer properties of DHM in OCs, indicating that DHM is a potential therapeutic agent for ovarian cancer through the inhibition of GRASP65 expression and the regulation of JNK/ERK pathway. |
| doi_str_mv | 10.1371/journal.pone.0225450 |
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Dihydromyricetin (DHM) has demonstrated antitumor activity in different types of human cancers. However, the pharmacological effects of DHM on ovarian cancer (OC) and the molecular mechanisms that underlie these effects are largely unknown. The present study showed that DHM reduced cell migration and invasion in a concentration- and time-dependent manner and induced cell apoptosis primarily through upregulation of Cleaved-caspase-3 and the Bax/Bcl-2 ratio in OCs. To further clarify the cancer therapeutic target, we assessed the effect of DHM on the expression of GRASP65, which is overexpressed in human ovarian cancer tissues. DHM activated caspase-3 and decreased GRASP65 expression to promote cell apoptosis, implying that downregulation of GRASP65 was related to DHM-induced cell apoptosis. Additionally, the knockdown of GRASP65 by siRNA resulted in increased apoptosis after DHM treatment, while western blot and flow cytometry analysis demonstrated that overexpression of GRASP65 attenuated DHM-mediated apoptosis. In addition, the JNK/ERK pathway may be involved in DHM-mediated caspase-3 activation and GRASP65 downregulation. Taken together, these findings provide novel evidence of the anti-cancer properties of DHM in OCs, indicating that DHM is a potential therapeutic agent for ovarian cancer through the inhibition of GRASP65 expression and the regulation of JNK/ERK pathway.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0225450</identifier><identifier>PMID: 31770410</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Anticancer properties ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Antitumor activity ; Apoptosis ; Apoptosis - drug effects ; BAX protein ; Bcl-2 protein ; Biology and Life Sciences ; Cancer cells ; Cancer prevention ; Cancer treatment ; Caspase 3 - genetics ; Caspase 3 - metabolism ; Caspase-3 ; Cell adhesion & migration ; Cell cycle ; Cell division ; Cell Line, Tumor ; Cell migration ; Cell Movement - drug effects ; Chemical compounds ; Chemotherapy ; Down-Regulation - drug effects ; Female ; Flavonols - pharmacology ; Flavonols - therapeutic use ; Flow cytometry ; Golgi cells ; Golgi Matrix Proteins - antagonists & inhibitors ; Golgi Matrix Proteins - genetics ; Golgi Matrix Proteins - metabolism ; Health aspects ; Hospitals ; Humans ; Ischemia ; Kinases ; Lung cancer ; MAP Kinase Signaling System - drug effects ; Medical equipment industry ; Medical prognosis ; Medical research ; Medicine and Health Sciences ; Metabolic pathways ; Metastasis ; Molecular modelling ; Morphology ; Novels ; Ovarian cancer ; Ovarian carcinoma ; Ovarian Neoplasms - drug therapy ; Ovarian Neoplasms - metabolism ; Pathology ; Pharmacology ; Phosphorylation ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Research and Analysis Methods ; RNA Interference ; RNA, Small Interfering - metabolism ; siRNA ; Stacking ; Therapeutic applications ; Time dependence ; Tumors ; Up-Regulation - drug effects</subject><ispartof>PloS one, 2019-11, Vol.14 (11), p.e0225450-e0225450</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Dihydromyricetin (DHM) has demonstrated antitumor activity in different types of human cancers. However, the pharmacological effects of DHM on ovarian cancer (OC) and the molecular mechanisms that underlie these effects are largely unknown. The present study showed that DHM reduced cell migration and invasion in a concentration- and time-dependent manner and induced cell apoptosis primarily through upregulation of Cleaved-caspase-3 and the Bax/Bcl-2 ratio in OCs. To further clarify the cancer therapeutic target, we assessed the effect of DHM on the expression of GRASP65, which is overexpressed in human ovarian cancer tissues. DHM activated caspase-3 and decreased GRASP65 expression to promote cell apoptosis, implying that downregulation of GRASP65 was related to DHM-induced cell apoptosis. Additionally, the knockdown of GRASP65 by siRNA resulted in increased apoptosis after DHM treatment, while western blot and flow cytometry analysis demonstrated that overexpression of GRASP65 attenuated DHM-mediated apoptosis. In addition, the JNK/ERK pathway may be involved in DHM-mediated caspase-3 activation and GRASP65 downregulation. Taken together, these findings provide novel evidence of the anti-cancer properties of DHM in OCs, indicating that DHM is a potential therapeutic agent for ovarian cancer through the inhibition of GRASP65 expression and the regulation of JNK/ERK pathway.</description><subject>Anticancer properties</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>BAX protein</subject><subject>Bcl-2 protein</subject><subject>Biology and Life Sciences</subject><subject>Cancer cells</subject><subject>Cancer prevention</subject><subject>Cancer treatment</subject><subject>Caspase 3 - genetics</subject><subject>Caspase 3 - metabolism</subject><subject>Caspase-3</subject><subject>Cell adhesion & migration</subject><subject>Cell cycle</subject><subject>Cell division</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cell Movement - drug effects</subject><subject>Chemical compounds</subject><subject>Chemotherapy</subject><subject>Down-Regulation - drug effects</subject><subject>Female</subject><subject>Flavonols - pharmacology</subject><subject>Flavonols - therapeutic use</subject><subject>Flow cytometry</subject><subject>Golgi cells</subject><subject>Golgi Matrix Proteins - antagonists & inhibitors</subject><subject>Golgi Matrix Proteins - genetics</subject><subject>Golgi Matrix Proteins - metabolism</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>MAP Kinase Signaling System - drug effects</subject><subject>Medical equipment industry</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Metabolic pathways</subject><subject>Metastasis</subject><subject>Molecular modelling</subject><subject>Morphology</subject><subject>Novels</subject><subject>Ovarian cancer</subject><subject>Ovarian carcinoma</subject><subject>Ovarian Neoplasms - drug therapy</subject><subject>Ovarian Neoplasms - metabolism</subject><subject>Pathology</subject><subject>Pharmacology</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Research and Analysis Methods</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - metabolism</subject><subject>siRNA</subject><subject>Stacking</subject><subject>Therapeutic applications</subject><subject>Time dependence</subject><subject>Tumors</subject><subject>Up-Regulation - drug effects</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk81u1DAUhSMEoqXwBggiISFYzGDnP5tKVQVlpEqV-Ntad-zrxIMTT22nMG_BI-N00mqCukBeXMv5znF87BtFLylZ0rSkHzZmsD3o5db0uCRJkmc5eRQd0zpNFkVC0scH86PomXMbQvK0Koqn0VFKy5JklBxHfy6MblRsEZzDbq13MfQidh74T9U38dYaj6qPizwW5ldvsRk0eGX6WLkguh6URRFLY2PfYpB6teDQc7QxSoncx0bGQrU7YU23s4qjD2ZB3Q4dhMkNWBXqJOGotXsePZGgHb6Y6kn0_dPHb-efF5dXF6vzs8sFL-rELwQmWQp5mZcSIQNO6lqKXPJSUAm8Knm2pgQlCljzVKwzxFACWlW8Cg6QnkSv975bbRybwnQsSWlVEpJlNBCrPSEMbNjWqg7sjhlQ7HbB2IaB9YprZITUnCRQkEwmWUmSWtYl0gTLIiVcCBK8TqfdhnWHgmPvLeiZ6fxLr1rWmBtWVGVNkzoYvJsMrLke0HnWKTcGBj2a4fa_a1rXIZuAvvkHffh0E9VAOIDqpQn78tGUnRWkqNKAjl7LB6gwBHaKh5cnVVifCd7PBIHx-Ns3MDjHVl-__D979WPOvj1gWwTtW2f0ML5FNwezPcitcc6ivA-ZEjY2zl0abGwcNjVOkL06vKB70V2npH8BFLgWzw</recordid><startdate>20191126</startdate><enddate>20191126</enddate><creator>Wang, Fengjie</creator><creator>Chen, Xianbing</creator><creator>Yuan, Depei</creator><creator>Yi, Yongfen</creator><creator>Luo, Yi</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-5084-842X</orcidid><orcidid>https://orcid.org/0000-0001-5587-0431</orcidid></search><sort><creationdate>20191126</creationdate><title>Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells</title><author>Wang, Fengjie ; Chen, Xianbing ; Yuan, Depei ; Yi, Yongfen ; Luo, Yi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-de243a5757fea4ac099fd5fc7d1fac87c4b10efedabc3db4eec3dfea88c8c69a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Anticancer properties</topic><topic>Antineoplastic Agents - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Fengjie</au><au>Chen, Xianbing</au><au>Yuan, Depei</au><au>Yi, Yongfen</au><au>Luo, Yi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-11-26</date><risdate>2019</risdate><volume>14</volume><issue>11</issue><spage>e0225450</spage><epage>e0225450</epage><pages>e0225450-e0225450</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Golgi reassembly and stacking protein 65 (GRASP65), which has been involved in cancer progression, is associated with tumor growth and cell apoptosis. Dihydromyricetin (DHM) has demonstrated antitumor activity in different types of human cancers. However, the pharmacological effects of DHM on ovarian cancer (OC) and the molecular mechanisms that underlie these effects are largely unknown. The present study showed that DHM reduced cell migration and invasion in a concentration- and time-dependent manner and induced cell apoptosis primarily through upregulation of Cleaved-caspase-3 and the Bax/Bcl-2 ratio in OCs. To further clarify the cancer therapeutic target, we assessed the effect of DHM on the expression of GRASP65, which is overexpressed in human ovarian cancer tissues. DHM activated caspase-3 and decreased GRASP65 expression to promote cell apoptosis, implying that downregulation of GRASP65 was related to DHM-induced cell apoptosis. Additionally, the knockdown of GRASP65 by siRNA resulted in increased apoptosis after DHM treatment, while western blot and flow cytometry analysis demonstrated that overexpression of GRASP65 attenuated DHM-mediated apoptosis. In addition, the JNK/ERK pathway may be involved in DHM-mediated caspase-3 activation and GRASP65 downregulation. Taken together, these findings provide novel evidence of the anti-cancer properties of DHM in OCs, indicating that DHM is a potential therapeutic agent for ovarian cancer through the inhibition of GRASP65 expression and the regulation of JNK/ERK pathway.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31770410</pmid><doi>10.1371/journal.pone.0225450</doi><tpages>e0225450</tpages><orcidid>https://orcid.org/0000-0001-5084-842X</orcidid><orcidid>https://orcid.org/0000-0001-5587-0431</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_2318700441 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Anticancer properties Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use Antitumor activity Apoptosis Apoptosis - drug effects BAX protein Bcl-2 protein Biology and Life Sciences Cancer cells Cancer prevention Cancer treatment Caspase 3 - genetics Caspase 3 - metabolism Caspase-3 Cell adhesion & migration Cell cycle Cell division Cell Line, Tumor Cell migration Cell Movement - drug effects Chemical compounds Chemotherapy Down-Regulation - drug effects Female Flavonols - pharmacology Flavonols - therapeutic use Flow cytometry Golgi cells Golgi Matrix Proteins - antagonists & inhibitors Golgi Matrix Proteins - genetics Golgi Matrix Proteins - metabolism Health aspects Hospitals Humans Ischemia Kinases Lung cancer MAP Kinase Signaling System - drug effects Medical equipment industry Medical prognosis Medical research Medicine and Health Sciences Metabolic pathways Metastasis Molecular modelling Morphology Novels Ovarian cancer Ovarian carcinoma Ovarian Neoplasms - drug therapy Ovarian Neoplasms - metabolism Pathology Pharmacology Phosphorylation Proteins Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism Research and Analysis Methods RNA Interference RNA, Small Interfering - metabolism siRNA Stacking Therapeutic applications Time dependence Tumors Up-Regulation - drug effects |
| title | Golgi reassembly and stacking protein 65 downregulation is required for the anti-cancer effect of dihydromyricetin on human ovarian cancer cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T21%3A45%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Golgi%20reassembly%20and%20stacking%20protein%2065%20downregulation%20is%20required%20for%20the%20anti-cancer%20effect%20of%20dihydromyricetin%20on%20human%20ovarian%20cancer%20cells&rft.jtitle=PloS%20one&rft.au=Wang,%20Fengjie&rft.date=2019-11-26&rft.volume=14&rft.issue=11&rft.spage=e0225450&rft.epage=e0225450&rft.pages=e0225450-e0225450&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0225450&rft_dat=%3Cgale_plos_%3EA606833182%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2318700441&rft_id=info:pmid/31770410&rft_galeid=A606833182&rft_doaj_id=oai_doaj_org_article_009c02a604f247029f97e12e7630cdd0&rfr_iscdi=true |