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Tetrahydrofurofuran-type lignans inhibit breast cancer-mediated bone destruction by blocking the vicious cycle between cancer cells, osteoblasts and osteoclasts

DC Field Value Language
dc.contributor.author박광균-
dc.contributor.author정원윤-
dc.contributor.author김현정-
dc.date.accessioned2015-01-06T16:25:34Z-
dc.date.available2015-01-06T16:25:34Z-
dc.date.issued2014-
dc.identifier.issn0167-6997-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/98082-
dc.description.abstractBreast cancer frequently spreads to bone. The interaction between bone metastases and microenvironment, referred as the “vicious cycle”, increases both tumor burden and bone destruction. Therefore, inhibition at any point in this “vicious cycle” can reduce malignant osteolytic lesions in patients with advanced breast cancer. In this study, we evaluated whether tetrahydrofurofuran-type lignans derived from Magnoliae Flos, commonly used in traditional Asian medicine to treat inflammatory diseases, could block breast cancer-mediated bone loss. Aschatin, fargesin, lirioresinol B dimethyl ether, and magnolin at noncytotoxic concentrations suppressed mRNA expression and secretion of osteolytic factor PTHrP in MDA-MB-231 metastatic human breast cancer cells. Fargesin inhibited TGF-β-stimulated cell viability, migration, and invasion and decreased TGF-β-induced PTHrP production in MDA-MB-231 cells. In addition, these lignans reduced RANKL/OPG ratio in PTHrP-treated hFOB1.19 human osteoblastic cells and inhibited RANKL-mediated osteoclast differentiation in mouse bone marrow macrophages. Aschatin, fargesin, lirioresinol B dimethyl ether, and magnolin substantially reduced bone-resorbing activity of osteoclasts by inhibiting MMP-9 and cathepsin K activities. Furthermore, orally administered fargesin inhibited tumor growth and cancer-mediated bone destruction in mice with MDA-MB-231 cells injected into calvarial tissues. Aschatin, fargesin, lirioresinol B dimethyl ether, and magnolin blocked initiation and progression of the “vicious cycle” between breast cancer metastases and bone microenvironment by inhibiting PTHrP production in breast cancer cells and osteoclastic bone resorption. Therefore, these tetrahydrofurofuran-type lignans have the potential to serve as beneficial agents to prevent and treat cancer-induced bone destruction in breast cancer patients.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfINVESTIGATIONAL NEW DRUGS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHBenzodioxoles/chemistry-
dc.subject.MESHBenzodioxoles/pharmacology-
dc.subject.MESHBenzodioxoles/therapeutic use-
dc.subject.MESHBone Resorption/drug therapy*-
dc.subject.MESHBone Resorption/etiology*-
dc.subject.MESHBreast Neoplasms/complications-
dc.subject.MESHBreast Neoplasms/drug therapy-
dc.subject.MESHBreast Neoplasms/pathology*-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHFemale-
dc.subject.MESHFurans/chemistry-
dc.subject.MESHFurans/pharmacology-
dc.subject.MESHFurans/therapeutic use*-
dc.subject.MESHGene Expression Regulation, Neoplastic/drug effects-
dc.subject.MESHHumans-
dc.subject.MESHLignans/chemistry-
dc.subject.MESHLignans/pharmacology-
dc.subject.MESHLignans/therapeutic use-
dc.subject.MESHLignin/chemistry-
dc.subject.MESHLignin/pharmacology-
dc.subject.MESHLignin/therapeutic use*-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred BALB C-
dc.subject.MESHMice, Nude-
dc.subject.MESHNeoplasm Metastasis-
dc.subject.MESHOsteoblasts/drug effects-
dc.subject.MESHOsteoblasts/metabolism-
dc.subject.MESHOsteoblasts/pathology*-
dc.subject.MESHOsteoclasts/drug effects-
dc.subject.MESHOsteoclasts/metabolism-
dc.subject.MESHOsteoclasts/pathology*-
dc.subject.MESHOsteoprotegerin/genetics-
dc.subject.MESHOsteoprotegerin/metabolism-
dc.subject.MESHParathyroid Hormone-Related Protein/biosynthesis-
dc.subject.MESHRANK Ligand/genetics-
dc.subject.MESHRANK Ligand/metabolism-
dc.subject.MESHRNA, Messenger/genetics-
dc.subject.MESHRNA, Messenger/metabolism-
dc.titleTetrahydrofurofuran-type lignans inhibit breast cancer-mediated bone destruction by blocking the vicious cycle between cancer cells, osteoblasts and osteoclasts-
dc.typeArticle-
dc.contributor.collegeCollege of Dentistry (치과대학)-
dc.contributor.departmentDept. of Oral Biology (구강생물학)-
dc.contributor.googleauthorAh Young Jun-
dc.contributor.googleauthorHyun-Jeong Kim-
dc.contributor.googleauthorKwang-Kyun Park-
dc.contributor.googleauthorKun Ho Son-
dc.contributor.googleauthorDong Hwa Lee-
dc.contributor.googleauthorMi-Hee Woo-
dc.contributor.googleauthorWon-Yoon Chung-
dc.identifier.doi10.1007/s10637-013-9969-0-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA01429-
dc.contributor.localIdA03676-
dc.relation.journalcodeJ01184-
dc.identifier.eissn1573-0646-
dc.identifier.pmid23673814-
dc.identifier.urlhttp://link.springer.com/article/10.1007%2Fs10637-013-9969-0-
dc.subject.keywordTetrahydrofurofuran-type lignans-
dc.subject.keywordBreast cancer-
dc.subject.keywordCancer-induced bone destruction-
dc.subject.keywordPTHrP-
dc.subject.keywordRANKL/OPG-
dc.subject.keywordOsteoclast-
dc.contributor.alternativeNamePark, Kwang Kyun-
dc.contributor.alternativeNameChung, Won Yoon-
dc.contributor.affiliatedAuthorPark, Kwang Kyun-
dc.contributor.affiliatedAuthorChung, Won Yoon-
dc.rights.accessRightsfree-
dc.citation.volume32-
dc.citation.startPage1-
dc.citation.endPage13-
dc.identifier.bibliographicCitationINVESTIGATIONAL NEW DRUGS, Vol.32 : 1-13, 2014-
dc.identifier.rimsid54875-
dc.type.rimsART-
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers

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