Germacrone Inhibits Cell Proliferation and Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cells
Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine Saussurea costus (SC). The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (...
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| Veröffentlicht in: | BioMed research international 2020, Vol.2020 (2020), p.1-13 |
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| creator | Yang, Xinzhou Wang, Qiang Wu, Qingming Yao, Fei Liu, Wanxin Guo, Kaiwen Hao, Ji Zhang, Ren Liu, Chang |
| description | Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine Saussurea costus (SC). The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (ESCC) are still unclear. Therefore, in this study, we further explored the internal molecular mechanism by which germacrone exerts its antiproliferation and antimigration ability against ESCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays showed that germacrone dose-dependently inhibited the proliferation of ESCC cells. Flow cytometry analysis (FACS) and wound healing experiments on germacrone treated ESCC cells showed that germacrone could induce apoptosis and inhibit the migration of ESCC cells in a dose-dependent manner. In the study on the mechanism of action of germacrone in antiesophageal cancer, we found that germacrone increased the ratio of Bax/Bcl-2 in the cytoplasm of ESCC, resulting in the activation of Caspase-9 and Caspase-3 and decreased the expression of Grp78, thereby reducing the inhibition of Caspase-12 and Caspase-7. In addition, we found that germacrone also inhibited STAT3 phosphorylation in a dose-dependent manner. In conclusion, we determined that germacrone exerted an antiesophageal effect through intrinsic apoptotic signaling pathways and by inhibiting STAT3 activity in ESCC cells. |
| doi_str_mv | 10.1155/2020/7643248 |
| format | Article |
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The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (ESCC) are still unclear. Therefore, in this study, we further explored the internal molecular mechanism by which germacrone exerts its antiproliferation and antimigration ability against ESCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays showed that germacrone dose-dependently inhibited the proliferation of ESCC cells. Flow cytometry analysis (FACS) and wound healing experiments on germacrone treated ESCC cells showed that germacrone could induce apoptosis and inhibit the migration of ESCC cells in a dose-dependent manner. In the study on the mechanism of action of germacrone in antiesophageal cancer, we found that germacrone increased the ratio of Bax/Bcl-2 in the cytoplasm of ESCC, resulting in the activation of Caspase-9 and Caspase-3 and decreased the expression of Grp78, thereby reducing the inhibition of Caspase-12 and Caspase-7. In addition, we found that germacrone also inhibited STAT3 phosphorylation in a dose-dependent manner. In conclusion, we determined that germacrone exerted an antiesophageal effect through intrinsic apoptotic signaling pathways and by inhibiting STAT3 activity in ESCC cells.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2020/7643248</identifier><identifier>PMID: 32071920</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Analysis ; Apoptosis ; Bcl-2 protein ; Cancer ; Cancer therapies ; Care and treatment ; Caspase-12 ; Caspase-3 ; Caspase-7 ; Caspase-9 ; Cell growth ; Cell migration ; Cell proliferation ; Chemotherapy ; Chromatography ; Cytoplasm ; Esophageal cancer ; Esophagus ; Ethanol ; Flow cytometry ; Herbal medicine ; Morphology ; Natural products ; Penicillin ; Pharmaceutical sciences ; Phosphorylation ; Sensors ; Software ; Squamous cell carcinoma ; Stat3 protein ; Traditional Chinese medicine ; Wound healing</subject><ispartof>BioMed research international, 2020, Vol.2020 (2020), p.1-13</ispartof><rights>Copyright © 2020 Ren Zhang et al.</rights><rights>COPYRIGHT 2020 John Wiley & Sons, Inc.</rights><rights>Copyright © 2020 Ren Zhang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2020 Ren Zhang et al. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-c0a74dd26437b7433637102b6a8792648a5679b9febc86a06377f9835639bbd13</citedby><cites>FETCH-LOGICAL-c499t-c0a74dd26437b7433637102b6a8792648a5679b9febc86a06377f9835639bbd13</cites><orcidid>0000-0001-9039-5146 ; 0000-0002-8009-1867 ; 0000-0001-7420-8646 ; 0000-0003-1697-2923</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011320/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011320/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32071920$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Daamen, Willeke F.</contributor><creatorcontrib>Yang, Xinzhou</creatorcontrib><creatorcontrib>Wang, Qiang</creatorcontrib><creatorcontrib>Wu, Qingming</creatorcontrib><creatorcontrib>Yao, Fei</creatorcontrib><creatorcontrib>Liu, Wanxin</creatorcontrib><creatorcontrib>Guo, Kaiwen</creatorcontrib><creatorcontrib>Hao, Ji</creatorcontrib><creatorcontrib>Zhang, Ren</creatorcontrib><creatorcontrib>Liu, Chang</creatorcontrib><title>Germacrone Inhibits Cell Proliferation and Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cells</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine Saussurea costus (SC). The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (ESCC) are still unclear. Therefore, in this study, we further explored the internal molecular mechanism by which germacrone exerts its antiproliferation and antimigration ability against ESCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays showed that germacrone dose-dependently inhibited the proliferation of ESCC cells. Flow cytometry analysis (FACS) and wound healing experiments on germacrone treated ESCC cells showed that germacrone could induce apoptosis and inhibit the migration of ESCC cells in a dose-dependent manner. In the study on the mechanism of action of germacrone in antiesophageal cancer, we found that germacrone increased the ratio of Bax/Bcl-2 in the cytoplasm of ESCC, resulting in the activation of Caspase-9 and Caspase-3 and decreased the expression of Grp78, thereby reducing the inhibition of Caspase-12 and Caspase-7. In addition, we found that germacrone also inhibited STAT3 phosphorylation in a dose-dependent manner. In conclusion, we determined that germacrone exerted an antiesophageal effect through intrinsic apoptotic signaling pathways and by inhibiting STAT3 activity in ESCC cells.</description><subject>Analysis</subject><subject>Apoptosis</subject><subject>Bcl-2 protein</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Care and treatment</subject><subject>Caspase-12</subject><subject>Caspase-3</subject><subject>Caspase-7</subject><subject>Caspase-9</subject><subject>Cell growth</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Chemotherapy</subject><subject>Chromatography</subject><subject>Cytoplasm</subject><subject>Esophageal cancer</subject><subject>Esophagus</subject><subject>Ethanol</subject><subject>Flow cytometry</subject><subject>Herbal medicine</subject><subject>Morphology</subject><subject>Natural products</subject><subject>Penicillin</subject><subject>Pharmaceutical sciences</subject><subject>Phosphorylation</subject><subject>Sensors</subject><subject>Software</subject><subject>Squamous cell carcinoma</subject><subject>Stat3 protein</subject><subject>Traditional Chinese medicine</subject><subject>Wound 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Inhibits Cell Proliferation and Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cells</title><author>Yang, Xinzhou ; Wang, Qiang ; Wu, Qingming ; Yao, Fei ; Liu, Wanxin ; Guo, Kaiwen ; Hao, Ji ; Zhang, Ren ; Liu, Chang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-c0a74dd26437b7433637102b6a8792648a5679b9febc86a06377f9835639bbd13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Apoptosis</topic><topic>Bcl-2 protein</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Care and treatment</topic><topic>Caspase-12</topic><topic>Caspase-3</topic><topic>Caspase-7</topic><topic>Caspase-9</topic><topic>Cell growth</topic><topic>Cell migration</topic><topic>Cell proliferation</topic><topic>Chemotherapy</topic><topic>Chromatography</topic><topic>Cytoplasm</topic><topic>Esophageal cancer</topic><topic>Esophagus</topic><topic>Ethanol</topic><topic>Flow cytometry</topic><topic>Herbal medicine</topic><topic>Morphology</topic><topic>Natural products</topic><topic>Penicillin</topic><topic>Pharmaceutical sciences</topic><topic>Phosphorylation</topic><topic>Sensors</topic><topic>Software</topic><topic>Squamous cell carcinoma</topic><topic>Stat3 protein</topic><topic>Traditional Chinese medicine</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Xinzhou</creatorcontrib><creatorcontrib>Wang, Qiang</creatorcontrib><creatorcontrib>Wu, Qingming</creatorcontrib><creatorcontrib>Yao, Fei</creatorcontrib><creatorcontrib>Liu, Wanxin</creatorcontrib><creatorcontrib>Guo, Kaiwen</creatorcontrib><creatorcontrib>Hao, Ji</creatorcontrib><creatorcontrib>Zhang, Ren</creatorcontrib><creatorcontrib>Liu, Chang</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical 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international</jtitle><addtitle>Biomed Res Int</addtitle><date>2020</date><risdate>2020</risdate><volume>2020</volume><issue>2020</issue><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>Germacrone, a natural 10-membered monocyclic sesquiterpene with three double bonds and a ketone, was isolated from the roots of traditional Chinese medicine Saussurea costus (SC). The pharmacological value and intrinsic mechanism of germacrone in the treatment of esophageal squamous cell carcinoma (ESCC) are still unclear. Therefore, in this study, we further explored the internal molecular mechanism by which germacrone exerts its antiproliferation and antimigration ability against ESCC. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assays showed that germacrone dose-dependently inhibited the proliferation of ESCC cells. Flow cytometry analysis (FACS) and wound healing experiments on germacrone treated ESCC cells showed that germacrone could induce apoptosis and inhibit the migration of ESCC cells in a dose-dependent manner. In the study on the mechanism of action of germacrone in antiesophageal cancer, we found that germacrone increased the ratio of Bax/Bcl-2 in the cytoplasm of ESCC, resulting in the activation of Caspase-9 and Caspase-3 and decreased the expression of Grp78, thereby reducing the inhibition of Caspase-12 and Caspase-7. In addition, we found that germacrone also inhibited STAT3 phosphorylation in a dose-dependent manner. In conclusion, we determined that germacrone exerted an antiesophageal effect through intrinsic apoptotic signaling pathways and by inhibiting STAT3 activity in ESCC cells.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>32071920</pmid><doi>10.1155/2020/7643248</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-9039-5146</orcidid><orcidid>https://orcid.org/0000-0002-8009-1867</orcidid><orcidid>https://orcid.org/0000-0001-7420-8646</orcidid><orcidid>https://orcid.org/0000-0003-1697-2923</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Apoptosis Bcl-2 protein Cancer Cancer therapies Care and treatment Caspase-12 Caspase-3 Caspase-7 Caspase-9 Cell growth Cell migration Cell proliferation Chemotherapy Chromatography Cytoplasm Esophageal cancer Esophagus Ethanol Flow cytometry Herbal medicine Morphology Natural products Penicillin Pharmaceutical sciences Phosphorylation Sensors Software Squamous cell carcinoma Stat3 protein Traditional Chinese medicine Wound healing |
| title | Germacrone Inhibits Cell Proliferation and Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cells |
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