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Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells

DC Field Value Language
dc.contributor.author천재희-
dc.contributor.author김원호-
dc.contributor.author김은수-
dc.contributor.author김태일-
dc.contributor.author김승원-
dc.date.accessioned2015-05-19T17:15:00Z-
dc.date.available2015-05-19T17:15:00Z-
dc.date.issued2008-
dc.identifier.issn1021-335X-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/107788-
dc.description.abstractThe plant sterol guggulsterone has been shown to exert anti-tumor effects, making it a candidate chemotherapeutic agent. We investigated the anti-tumor effects of guggulsterone on colon cancer cells and elucidated the underlying molecular mechanisms related to angiogenesis. The apoptotic effects of guggulsterone were examined by cell survival assay. Western blot analysis was used to determine the levels of various down-stream intracellular proteins involved in angiogenesis, including signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1alpha (HIF-1alpha) and aryl hydrocarbon receptor nuclear translocator (ARNT). Using chromatin immunoprecipitation assay, we tested whether guggulsterone affects the recruitment of STAT3, ARNT and HIF-1alpha to the human VEGF promoter. To investigate the effect of guggulsterone on vascular endothelial cell migration and invasion, tube formation and migration assays were conducted using human umbilical vein endothelial cells (HUVECs). Matrix metalloproteinase (MMP)-2 and -9 activities were measured by gelatin zymography. Guggulsterone significantly reduced cell viability in colon cancer cells in a dose-dependent manner and blocked VEGF, ARNT and STAT3 expression prominently in hypoxic conditions. The recruitment of STAT3 and ARNT, but not HIF-1alpha, to the VEGF promoter was inhibited by guggulsterone treatment. HUVECs produced much foreshortened and severely broken tubes and showed decreased migration activity under guggulsterone effects. In addition, zymography revealed that MMP-2 and -9 enzyme activities were markedly lower in the presence of guggulsterone. The results of this study suggest that guggulsterone not only induces apoptosis, but also inhibits angiogenesis and metastasis in colon cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of colorectal cancer.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfONCOLOGY REPORTS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAngiogenesis Inhibitors/pharmacology-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHCell Movement-
dc.subject.MESHColonic Neoplasms/drug therapy-
dc.subject.MESHColonic Neoplasms/metabolism*-
dc.subject.MESHEndothelium, Vascular/metabolism-
dc.subject.MESHGene Expression Regulation, Neoplastic*-
dc.subject.MESHHumans-
dc.subject.MESHModels, Biological-
dc.subject.MESHNeoplasm Metastasis-
dc.subject.MESHNeovascularization, Pathologic*-
dc.subject.MESHPregnenediones/pharmacology*-
dc.subject.MESHPromoter Regions, Genetic-
dc.subject.MESHSTAT3 Transcription Factor/metabolism*-
dc.subject.MESHTetrazolium Salts/pharmacology-
dc.subject.MESHThiazoles/pharmacology-
dc.subject.MESHVascular Endothelial Growth Factor A/metabolism*-
dc.titleGuggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorEUN SOO KIM-
dc.contributor.googleauthorSUNG YI HONG-
dc.contributor.googleauthorHYE KYUNG LEE-
dc.contributor.googleauthorSEUNG WON KIM-
dc.contributor.googleauthorMIN JI AN-
dc.contributor.googleauthorTAE IL KIM-
dc.contributor.googleauthorKYOUNG RYUL LEE-
dc.contributor.googleauthorWON HO KIM-
dc.contributor.googleauthorJAE HEE CHEON-
dc.identifier.doi10.3892/or_00000147-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00774-
dc.contributor.localIdA01079-
dc.contributor.localIdA00804-
dc.contributor.localIdA04030-
dc.relation.journalcodeJ02419-
dc.identifier.eissn1791-2431-
dc.identifier.pmid19020709-
dc.identifier.urlhttp://www.spandidos-publications.com/or/20/6/1321-
dc.subject.keywordAngiogenesis Inhibitors/pharmacology-
dc.subject.keywordCell Line, Tumor-
dc.subject.keywordCell Movement-
dc.subject.keywordColonic Neoplasms/drug therapy-
dc.subject.keywordColonic Neoplasms/metabolism*-
dc.subject.keywordEndothelium, Vascular/metabolism-
dc.subject.keywordGene Expression Regulation, Neoplastic*-
dc.subject.keywordHumans-
dc.subject.keywordModels, Biological-
dc.subject.keywordNeoplasm Metastasis-
dc.subject.keywordNeovascularization, Pathologic*-
dc.subject.keywordPregnenediones/pharmacology*-
dc.subject.keywordPromoter Regions, Genetic-
dc.subject.keywordSTAT3 Transcription Factor/metabolism*-
dc.subject.keywordTetrazolium Salts/pharmacology-
dc.subject.keywordThiazoles/pharmacology-
dc.subject.keywordVascular Endothelial Growth Factor A/metabolism*-
dc.contributor.alternativeNameCheon, Jae Hee-
dc.contributor.alternativeNameKim, Won Ho-
dc.contributor.alternativeNameKim, Eun Soo-
dc.contributor.alternativeNameKim, Tae Il-
dc.contributor.affiliatedAuthorKim, Won Ho-
dc.contributor.affiliatedAuthorKim, Tae Il-
dc.contributor.affiliatedAuthorKim, Eun Soo-
dc.contributor.affiliatedAuthorCheon, Jae Hee-
dc.rights.accessRightsnot free-
dc.citation.volume20-
dc.citation.number6-
dc.citation.startPage1321-
dc.citation.endPage1327-
dc.identifier.bibliographicCitationONCOLOGY REPORTS, Vol.20(6) : 1321-1327, 2008-
dc.identifier.rimsid34685-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers

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