Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma
Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell lines Hep G2 and P...
Gespeichert in:
| Veröffentlicht in: | Oncology reports 2013-01, Vol.29 (1), p.103-108 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 108 |
|---|---|
| container_issue | 1 |
| container_start_page | 103 |
| container_title | Oncology reports |
| container_volume | 29 |
| creator | HE, LIHUA YANG, XIAOHONG CAO, XIAOCHENG LIU, FEI QUAN, MEIFANG CAO, JIANGUO |
| description | Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell lines Hep G2 and PLC/PRF/5 were cultured in vitro. The growth inhibitory effects of casticin were evaluated using clonogenic assays. The distribution of phases in the cell cycle was analyzed using flow cytometry (FCM) analysis with propidium iodide (PI) staining. Multiple molecular techniques, such as western blotting and gene transfection, were used to explore the molecular mechanisms of action. Our data demonstrated that casticin significantly inhibited cell viability and colony formation in HCC cells. Furthermore, it induced cell cycle arrest in the G2/M phase. Casticin inhibited phosphorylation of the FOXO3a protein and decreased the expression of FoxM1 and its downstream genes, such as cyclin-dependent kinase (CDK1), CDC25B and cyclin B and increased the expression of p27KIP1. Silencing of FOXO3a expression by small interfering RNA (siRNA) transfection clearly attenuated the inhibitory effects of casticin on FOXM1 expression and cell growth. Our findings provided clear evidence that casticin induces growth suppression and cell cycle arrest through inhibition of FOXO3a phosphorylation causing inactivation of FOXM1 in HCC cells. |
| doi_str_mv | 10.3892/or.2012.2076 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1151034043</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1151034043</sourcerecordid><originalsourceid>FETCH-LOGICAL-c388t-53dda9ff77fe0864d1c0e964a9a9df772cd5a078aa57468a4e969fa774481fdc3</originalsourceid><addsrcrecordid>eNpdkUtLxDAUhYMozvjYuZaAIC7smFebZimDo4IwG4XZhWuSOpVOU5NWmX9vyqgLISQh97snh3sQOqNkxkvFbnyYMUJZ2mSxh6ZUKpoxwel-uhNGM87z1QQdxfhOCJOkUIdowjgphGBkisIcYl-busV1awfjIn4L_qtf4zh0XXAx1r7F0FpsXNNgszWNwxBSocf9OvjhbY3B9PUn9CPoK7xYrpYckhpeuw56P_YNDQRsIKRv_AZO0EEFTXSnP-cxelncPc8fsqfl_eP89ikzvCz7LOfWgqoqKStHykJYaohThQAFyqZXZmwORJYAuRRFCSIVVQVSClHSyhp-jK52ul3wH0NyrDd1HO1A6_wQNaU5JVwQwRN68Q9990NokztNFWdFXlAhEnW9o0zwMQZX6S7UGwhbTYkes9A-6DELPWaR8PMf0eF14-wf_Dv8BFzugNilCdfWxz_Gh4ypjNC0COffVBmSOQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1932656144</pqid></control><display><type>article</type><title>Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>HE, LIHUA ; YANG, XIAOHONG ; CAO, XIAOCHENG ; LIU, FEI ; QUAN, MEIFANG ; CAO, JIANGUO</creator><creatorcontrib>HE, LIHUA ; YANG, XIAOHONG ; CAO, XIAOCHENG ; LIU, FEI ; QUAN, MEIFANG ; CAO, JIANGUO</creatorcontrib><description>Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell lines Hep G2 and PLC/PRF/5 were cultured in vitro. The growth inhibitory effects of casticin were evaluated using clonogenic assays. The distribution of phases in the cell cycle was analyzed using flow cytometry (FCM) analysis with propidium iodide (PI) staining. Multiple molecular techniques, such as western blotting and gene transfection, were used to explore the molecular mechanisms of action. Our data demonstrated that casticin significantly inhibited cell viability and colony formation in HCC cells. Furthermore, it induced cell cycle arrest in the G2/M phase. Casticin inhibited phosphorylation of the FOXO3a protein and decreased the expression of FoxM1 and its downstream genes, such as cyclin-dependent kinase (CDK1), CDC25B and cyclin B and increased the expression of p27KIP1. Silencing of FOXO3a expression by small interfering RNA (siRNA) transfection clearly attenuated the inhibitory effects of casticin on FOXM1 expression and cell growth. Our findings provided clear evidence that casticin induces growth suppression and cell cycle arrest through inhibition of FOXO3a phosphorylation causing inactivation of FOXM1 in HCC cells.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2012.2076</identifier><identifier>PMID: 23064420</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Apoptosis ; Blotting, Western ; Cancer therapies ; Carcinoma, Hepatocellular - drug therapy ; Carcinoma, Hepatocellular - metabolism ; Carcinoma, Hepatocellular - pathology ; casticin ; Cell cycle ; Cell Cycle Checkpoints - drug effects ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cyclin B - metabolism ; Cyclin-Dependent Kinase Inhibitor p27 - metabolism ; Cyclin-dependent kinases ; Flavonoids - pharmacology ; Forkhead Box Protein M1 ; Forkhead Box Protein O3 ; Forkhead Transcription Factors - antagonists & inhibitors ; Forkhead Transcription Factors - genetics ; Forkhead Transcription Factors - metabolism ; FOXM1 ; FOXO3a ; Gene Expression Regulation, Neoplastic ; hepatocellular carcinoma ; Humans ; Investigations ; Kinases ; Liver cancer ; Liver Neoplasms - drug therapy ; Liver Neoplasms - metabolism ; Liver Neoplasms - pathology ; Medical prognosis ; Phosphorylation ; Proto-Oncogene Proteins c-akt - metabolism ; RNA, Small Interfering - genetics ; Transcription factors ; Tumor Cells, Cultured</subject><ispartof>Oncology reports, 2013-01, Vol.29 (1), p.103-108</ispartof><rights>Copyright © 2013, Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-53dda9ff77fe0864d1c0e964a9a9df772cd5a078aa57468a4e969fa774481fdc3</citedby><cites>FETCH-LOGICAL-c388t-53dda9ff77fe0864d1c0e964a9a9df772cd5a078aa57468a4e969fa774481fdc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23064420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>HE, LIHUA</creatorcontrib><creatorcontrib>YANG, XIAOHONG</creatorcontrib><creatorcontrib>CAO, XIAOCHENG</creatorcontrib><creatorcontrib>LIU, FEI</creatorcontrib><creatorcontrib>QUAN, MEIFANG</creatorcontrib><creatorcontrib>CAO, JIANGUO</creatorcontrib><title>Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell lines Hep G2 and PLC/PRF/5 were cultured in vitro. The growth inhibitory effects of casticin were evaluated using clonogenic assays. The distribution of phases in the cell cycle was analyzed using flow cytometry (FCM) analysis with propidium iodide (PI) staining. Multiple molecular techniques, such as western blotting and gene transfection, were used to explore the molecular mechanisms of action. Our data demonstrated that casticin significantly inhibited cell viability and colony formation in HCC cells. Furthermore, it induced cell cycle arrest in the G2/M phase. Casticin inhibited phosphorylation of the FOXO3a protein and decreased the expression of FoxM1 and its downstream genes, such as cyclin-dependent kinase (CDK1), CDC25B and cyclin B and increased the expression of p27KIP1. Silencing of FOXO3a expression by small interfering RNA (siRNA) transfection clearly attenuated the inhibitory effects of casticin on FOXM1 expression and cell growth. Our findings provided clear evidence that casticin induces growth suppression and cell cycle arrest through inhibition of FOXO3a phosphorylation causing inactivation of FOXM1 in HCC cells.</description><subject>Apoptosis</subject><subject>Blotting, Western</subject><subject>Cancer therapies</subject><subject>Carcinoma, Hepatocellular - drug therapy</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>casticin</subject><subject>Cell cycle</subject><subject>Cell Cycle Checkpoints - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Cyclin B - metabolism</subject><subject>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</subject><subject>Cyclin-dependent kinases</subject><subject>Flavonoids - pharmacology</subject><subject>Forkhead Box Protein M1</subject><subject>Forkhead Box Protein O3</subject><subject>Forkhead Transcription Factors - antagonists & inhibitors</subject><subject>Forkhead Transcription Factors - genetics</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>FOXM1</subject><subject>FOXO3a</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>hepatocellular carcinoma</subject><subject>Humans</subject><subject>Investigations</subject><subject>Kinases</subject><subject>Liver cancer</subject><subject>Liver Neoplasms - drug therapy</subject><subject>Liver Neoplasms - metabolism</subject><subject>Liver Neoplasms - pathology</subject><subject>Medical prognosis</subject><subject>Phosphorylation</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>Transcription factors</subject><subject>Tumor Cells, Cultured</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpdkUtLxDAUhYMozvjYuZaAIC7smFebZimDo4IwG4XZhWuSOpVOU5NWmX9vyqgLISQh97snh3sQOqNkxkvFbnyYMUJZ2mSxh6ZUKpoxwel-uhNGM87z1QQdxfhOCJOkUIdowjgphGBkisIcYl-busV1awfjIn4L_qtf4zh0XXAx1r7F0FpsXNNgszWNwxBSocf9OvjhbY3B9PUn9CPoK7xYrpYckhpeuw56P_YNDQRsIKRv_AZO0EEFTXSnP-cxelncPc8fsqfl_eP89ikzvCz7LOfWgqoqKStHykJYaohThQAFyqZXZmwORJYAuRRFCSIVVQVSClHSyhp-jK52ul3wH0NyrDd1HO1A6_wQNaU5JVwQwRN68Q9990NokztNFWdFXlAhEnW9o0zwMQZX6S7UGwhbTYkes9A-6DELPWaR8PMf0eF14-wf_Dv8BFzugNilCdfWxz_Gh4ypjNC0COffVBmSOQ</recordid><startdate>201301</startdate><enddate>201301</enddate><creator>HE, LIHUA</creator><creator>YANG, XIAOHONG</creator><creator>CAO, XIAOCHENG</creator><creator>LIU, FEI</creator><creator>QUAN, MEIFANG</creator><creator>CAO, JIANGUO</creator><general>D.A. Spandidos</general><general>Spandidos Publications UK Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201301</creationdate><title>Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma</title><author>HE, LIHUA ; YANG, XIAOHONG ; CAO, XIAOCHENG ; LIU, FEI ; QUAN, MEIFANG ; CAO, JIANGUO</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c388t-53dda9ff77fe0864d1c0e964a9a9df772cd5a078aa57468a4e969fa774481fdc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Apoptosis</topic><topic>Blotting, Western</topic><topic>Cancer therapies</topic><topic>Carcinoma, Hepatocellular - drug therapy</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>casticin</topic><topic>Cell cycle</topic><topic>Cell Cycle Checkpoints - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cyclin B - metabolism</topic><topic>Cyclin-Dependent Kinase Inhibitor p27 - metabolism</topic><topic>Cyclin-dependent kinases</topic><topic>Flavonoids - pharmacology</topic><topic>Forkhead Box Protein M1</topic><topic>Forkhead Box Protein O3</topic><topic>Forkhead Transcription Factors - antagonists & inhibitors</topic><topic>Forkhead Transcription Factors - genetics</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>FOXM1</topic><topic>FOXO3a</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>hepatocellular carcinoma</topic><topic>Humans</topic><topic>Investigations</topic><topic>Kinases</topic><topic>Liver cancer</topic><topic>Liver Neoplasms - drug therapy</topic><topic>Liver Neoplasms - metabolism</topic><topic>Liver Neoplasms - pathology</topic><topic>Medical prognosis</topic><topic>Phosphorylation</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>Transcription factors</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>HE, LIHUA</creatorcontrib><creatorcontrib>YANG, XIAOHONG</creatorcontrib><creatorcontrib>CAO, XIAOCHENG</creatorcontrib><creatorcontrib>LIU, FEI</creatorcontrib><creatorcontrib>QUAN, MEIFANG</creatorcontrib><creatorcontrib>CAO, JIANGUO</creatorcontrib><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>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>British Nursing Database</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical 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><jtitle>Oncology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>HE, LIHUA</au><au>YANG, XIAOHONG</au><au>CAO, XIAOCHENG</au><au>LIU, FEI</au><au>QUAN, MEIFANG</au><au>CAO, JIANGUO</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma</atitle><jtitle>Oncology reports</jtitle><addtitle>Oncol Rep</addtitle><date>2013-01</date><risdate>2013</risdate><volume>29</volume><issue>1</issue><spage>103</spage><epage>108</epage><pages>103-108</pages><issn>1021-335X</issn><eissn>1791-2431</eissn><abstract>Casticin, a polymethoxyflavone, has been reported to exert anticancer activities. The objectives of this study were to examine the molecular mechanisms by which casticin induces the growth inhibition and cell cycle arrest in human hepatocellular carcinoma (HCC) cells. The HCC cell lines Hep G2 and PLC/PRF/5 were cultured in vitro. The growth inhibitory effects of casticin were evaluated using clonogenic assays. The distribution of phases in the cell cycle was analyzed using flow cytometry (FCM) analysis with propidium iodide (PI) staining. Multiple molecular techniques, such as western blotting and gene transfection, were used to explore the molecular mechanisms of action. Our data demonstrated that casticin significantly inhibited cell viability and colony formation in HCC cells. Furthermore, it induced cell cycle arrest in the G2/M phase. Casticin inhibited phosphorylation of the FOXO3a protein and decreased the expression of FoxM1 and its downstream genes, such as cyclin-dependent kinase (CDK1), CDC25B and cyclin B and increased the expression of p27KIP1. Silencing of FOXO3a expression by small interfering RNA (siRNA) transfection clearly attenuated the inhibitory effects of casticin on FOXM1 expression and cell growth. Our findings provided clear evidence that casticin induces growth suppression and cell cycle arrest through inhibition of FOXO3a phosphorylation causing inactivation of FOXM1 in HCC cells.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>23064420</pmid><doi>10.3892/or.2012.2076</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1021-335X |
| ispartof | Oncology reports, 2013-01, Vol.29 (1), p.103-108 |
| issn | 1021-335X 1791-2431 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1151034043 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Apoptosis Blotting, Western Cancer therapies Carcinoma, Hepatocellular - drug therapy Carcinoma, Hepatocellular - metabolism Carcinoma, Hepatocellular - pathology casticin Cell cycle Cell Cycle Checkpoints - drug effects Cell Proliferation - drug effects Cell Survival - drug effects Cyclin B - metabolism Cyclin-Dependent Kinase Inhibitor p27 - metabolism Cyclin-dependent kinases Flavonoids - pharmacology Forkhead Box Protein M1 Forkhead Box Protein O3 Forkhead Transcription Factors - antagonists & inhibitors Forkhead Transcription Factors - genetics Forkhead Transcription Factors - metabolism FOXM1 FOXO3a Gene Expression Regulation, Neoplastic hepatocellular carcinoma Humans Investigations Kinases Liver cancer Liver Neoplasms - drug therapy Liver Neoplasms - metabolism Liver Neoplasms - pathology Medical prognosis Phosphorylation Proto-Oncogene Proteins c-akt - metabolism RNA, Small Interfering - genetics Transcription factors Tumor Cells, Cultured |
| title | Casticin induces growth suppression and cell cycle arrest through activation of FOXO3a in hepatocellular carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T17%3A47%3A52IST&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=Casticin%20induces%20growth%20suppression%20and%20cell%20cycle%20arrest%20through%20activation%20of%20FOXO3a%20in%20hepatocellular%20carcinoma&rft.jtitle=Oncology%20reports&rft.au=HE,%20LIHUA&rft.date=2013-01&rft.volume=29&rft.issue=1&rft.spage=103&rft.epage=108&rft.pages=103-108&rft.issn=1021-335X&rft.eissn=1791-2431&rft_id=info:doi/10.3892/or.2012.2076&rft_dat=%3Cproquest_cross%3E1151034043%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=1932656144&rft_id=info:pmid/23064420&rfr_iscdi=true |