Ganoderma lucidum Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway
Background: Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine. Ganoderma lucidum, a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its...
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| Veröffentlicht in: | Integrative cancer therapies 2019, Vol.18, p.1534735419890917-1534735419890917 |
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| creator | Zhang, Qi-Hao Hu, Qin-Xiao Xie, Da Chang, Bo Miao, Hou-Guang Wang, Yun-Guo Liu, De-Zhong Li, Xue-Dong |
| description | Background: Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine. Ganoderma lucidum, a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells. Objective: To investigate the effect of G lucidum on osteosarcoma cells and its mechanism. Methods: Osteosarcoma MG63 and U2-OS cells were treated with G lucidum, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect of G lucidum on Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay. Results: G lucidum inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed that G lucidum suppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover, G lucidum blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated. Conclusions: Our results suggest that G lucidum broadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling. |
| doi_str_mv | 10.1177/1534735419890917 |
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Ganoderma lucidum, a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells. Objective: To investigate the effect of G lucidum on osteosarcoma cells and its mechanism. Methods: Osteosarcoma MG63 and U2-OS cells were treated with G lucidum, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect of G lucidum on Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay. Results: G lucidum inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed that G lucidum suppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover, G lucidum blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated. Conclusions: Our results suggest that G lucidum broadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.</description><identifier>ISSN: 1534-7354</identifier><identifier>EISSN: 1552-695X</identifier><identifier>DOI: 10.1177/1534735419890917</identifier><identifier>PMID: 31855073</identifier><language>eng</language><publisher>Los Angeles, CA: SAGE Publications</publisher><subject>Annexin V ; Antitumor activity ; Apoptosis ; Apoptosis - drug effects ; beta Catenin - metabolism ; Biological Products - pharmacology ; Bone cancer ; c-Myc protein ; Cell Cycle - drug effects ; Cell Death - drug effects ; Cell growth ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Chinese medicine ; Cyclin D1 ; E-cadherin ; Flow cytometry ; Ganoderma lucidum ; Gelatinase A ; Gelatinase B ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Leukocyte migration ; LRP5 protein ; Lymphocytes T ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Molecular modelling ; Myc protein ; Osteosarcoma ; Osteosarcoma - drug therapy ; Osteosarcoma - metabolism ; Osteosarcoma cells ; Polymerase chain reaction ; Propidium iodide ; Reishi - chemistry ; Sarcoma ; Signal transduction ; Traditional Chinese medicine ; Transcription factors ; Wnt Signaling Pathway - drug effects ; Wound healing</subject><ispartof>Integrative cancer therapies, 2019, Vol.18, p.1534735419890917-1534735419890917</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is licensed under the Creative Commons Attribution – Non-Commercial License https://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2019 2019 SAGE Publications</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c462t-575cfa8c5b0379f11dac1202c59b967180a01bee763b97bec42d6f3310fd4a943</citedby><cites>FETCH-LOGICAL-c462t-575cfa8c5b0379f11dac1202c59b967180a01bee763b97bec42d6f3310fd4a943</cites><orcidid>0000-0001-6482-9369</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/PMC6923688/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923688/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,4022,21965,27852,27922,27923,27924,44944,45332,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31855073$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Qi-Hao</creatorcontrib><creatorcontrib>Hu, Qin-Xiao</creatorcontrib><creatorcontrib>Xie, Da</creatorcontrib><creatorcontrib>Chang, Bo</creatorcontrib><creatorcontrib>Miao, Hou-Guang</creatorcontrib><creatorcontrib>Wang, Yun-Guo</creatorcontrib><creatorcontrib>Liu, De-Zhong</creatorcontrib><creatorcontrib>Li, Xue-Dong</creatorcontrib><title>Ganoderma lucidum Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway</title><title>Integrative cancer therapies</title><addtitle>Integr Cancer Ther</addtitle><description>Background: Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine. Ganoderma lucidum, a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells. Objective: To investigate the effect of G lucidum on osteosarcoma cells and its mechanism. Methods: Osteosarcoma MG63 and U2-OS cells were treated with G lucidum, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect of G lucidum on Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay. Results: G lucidum inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed that G lucidum suppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover, G lucidum blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated. Conclusions: Our results suggest that G lucidum broadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.</description><subject>Annexin V</subject><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>beta Catenin - metabolism</subject><subject>Biological Products - pharmacology</subject><subject>Bone cancer</subject><subject>c-Myc protein</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Death - drug effects</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Chinese medicine</subject><subject>Cyclin D1</subject><subject>E-cadherin</subject><subject>Flow cytometry</subject><subject>Ganoderma lucidum</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Leukocyte migration</subject><subject>LRP5 protein</subject><subject>Lymphocytes T</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Molecular modelling</subject><subject>Myc protein</subject><subject>Osteosarcoma</subject><subject>Osteosarcoma - drug therapy</subject><subject>Osteosarcoma - metabolism</subject><subject>Osteosarcoma cells</subject><subject>Polymerase chain reaction</subject><subject>Propidium iodide</subject><subject>Reishi - chemistry</subject><subject>Sarcoma</subject><subject>Signal transduction</subject><subject>Traditional Chinese medicine</subject><subject>Transcription factors</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>Wound healing</subject><issn>1534-7354</issn><issn>1552-695X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>AFRWT</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNp1kc9qFTEYxQdRbK3uXUnAjZux-TOZTDZCuVxboVChiu7CN5lv7k2ZSa5JptqND-WD-EzOcGvVgqsEzu-c5HCK4jmjrxlT6phJUSkhK6YbTTVTD4pDJiUvay0_P1zuoioX_aB4ktIVpZzRWj4uDgRrpKRKHBbfT8GHDuMIZJis66aRrL9hzImAJyc-OwveYiTrvkebSfDkbBpn6SJlDAmiDbNzhcOQyLUDcjntdhFTcn5D8hbJJ5-Pf_4oV5DRO08u3cbDsIjvIW-_ws3T4lEPQ8Jnt-dR8fHt-sPqrDy_OH23OjkvbVXzXEolbQ-NlS0VSveMdWAZp9xK3epasYYCZS2iqkWrVYu24l3dC8Fo31WgK3FUvNnn7qZ2xM6izxEGs4tuhHhjAjjzr-Ld1mzCtak1F3XTzAGvbgNi-DJhymZ0yc69wWOYkuGCN0qrRtIZfXkPvQpTnHsvlGBSS60Wiu4pG0NKEfu7zzBqlnHN_XFny4u_S9wZfq85A-UeSLDBP6_-N_AXhZiung</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Zhang, Qi-Hao</creator><creator>Hu, Qin-Xiao</creator><creator>Xie, Da</creator><creator>Chang, Bo</creator><creator>Miao, Hou-Guang</creator><creator>Wang, Yun-Guo</creator><creator>Liu, De-Zhong</creator><creator>Li, Xue-Dong</creator><general>SAGE Publications</general><general>SAGE PUBLICATIONS, INC</general><scope>AFRWT</scope><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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>KB0</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6482-9369</orcidid></search><sort><creationdate>2019</creationdate><title>Ganoderma lucidum Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway</title><author>Zhang, Qi-Hao ; Hu, Qin-Xiao ; Xie, Da ; Chang, Bo ; Miao, Hou-Guang ; Wang, Yun-Guo ; Liu, De-Zhong ; Li, Xue-Dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c462t-575cfa8c5b0379f11dac1202c59b967180a01bee763b97bec42d6f3310fd4a943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Annexin V</topic><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>beta Catenin - metabolism</topic><topic>Biological Products - pharmacology</topic><topic>Bone cancer</topic><topic>c-Myc protein</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Death - drug effects</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Chinese medicine</topic><topic>Cyclin D1</topic><topic>E-cadherin</topic><topic>Flow cytometry</topic><topic>Ganoderma lucidum</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>Leukocyte migration</topic><topic>LRP5 protein</topic><topic>Lymphocytes T</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Molecular modelling</topic><topic>Myc protein</topic><topic>Osteosarcoma</topic><topic>Osteosarcoma - drug therapy</topic><topic>Osteosarcoma - metabolism</topic><topic>Osteosarcoma cells</topic><topic>Polymerase chain reaction</topic><topic>Propidium iodide</topic><topic>Reishi - chemistry</topic><topic>Sarcoma</topic><topic>Signal transduction</topic><topic>Traditional Chinese medicine</topic><topic>Transcription factors</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Qi-Hao</creatorcontrib><creatorcontrib>Hu, Qin-Xiao</creatorcontrib><creatorcontrib>Xie, Da</creatorcontrib><creatorcontrib>Chang, Bo</creatorcontrib><creatorcontrib>Miao, Hou-Guang</creatorcontrib><creatorcontrib>Wang, Yun-Guo</creatorcontrib><creatorcontrib>Liu, De-Zhong</creatorcontrib><creatorcontrib>Li, Xue-Dong</creatorcontrib><collection>Sage Journals GOLD Open Access 2024</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Integrative cancer therapies</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Qi-Hao</au><au>Hu, Qin-Xiao</au><au>Xie, Da</au><au>Chang, Bo</au><au>Miao, Hou-Guang</au><au>Wang, Yun-Guo</au><au>Liu, De-Zhong</au><au>Li, Xue-Dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ganoderma lucidum Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway</atitle><jtitle>Integrative cancer therapies</jtitle><addtitle>Integr Cancer Ther</addtitle><date>2019</date><risdate>2019</risdate><volume>18</volume><spage>1534735419890917</spage><epage>1534735419890917</epage><pages>1534735419890917-1534735419890917</pages><issn>1534-7354</issn><eissn>1552-695X</eissn><abstract>Background: Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine. Ganoderma lucidum, a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells. Objective: To investigate the effect of G lucidum on osteosarcoma cells and its mechanism. Methods: Osteosarcoma MG63 and U2-OS cells were treated with G lucidum, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect of G lucidum on Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay. Results: G lucidum inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed that G lucidum suppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover, G lucidum blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated. Conclusions: Our results suggest that G lucidum broadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.</abstract><cop>Los Angeles, CA</cop><pub>SAGE Publications</pub><pmid>31855073</pmid><doi>10.1177/1534735419890917</doi><orcidid>https://orcid.org/0000-0001-6482-9369</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Annexin V Antitumor activity Apoptosis Apoptosis - drug effects beta Catenin - metabolism Biological Products - pharmacology Bone cancer c-Myc protein Cell Cycle - drug effects Cell Death - drug effects Cell growth Cell Line, Tumor Cell Movement - drug effects Cell proliferation Cell Proliferation - drug effects Chinese medicine Cyclin D1 E-cadherin Flow cytometry Ganoderma lucidum Gelatinase A Gelatinase B Gene Expression Regulation, Neoplastic - drug effects Humans Leukocyte migration LRP5 protein Lymphocytes T Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Molecular modelling Myc protein Osteosarcoma Osteosarcoma - drug therapy Osteosarcoma - metabolism Osteosarcoma cells Polymerase chain reaction Propidium iodide Reishi - chemistry Sarcoma Signal transduction Traditional Chinese medicine Transcription factors Wnt Signaling Pathway - drug effects Wound healing |
| title | Ganoderma lucidum Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway |
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