Cited 77 times in
Kalopanaxsaponin A inhibits PMA-induced invasion by reducing matrix metalloproteinase-9 via PI3K/Akt- and PKCdelta-mediated signaling in MCF-7 human breast cancer cells
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 박광균 | - |
dc.contributor.author | 정원윤 | - |
dc.contributor.author | 황영선 | - |
dc.date.accessioned | 2015-04-24T16:59:55Z | - |
dc.date.available | 2015-04-24T16:59:55Z | - |
dc.date.issued | 2009 | - |
dc.identifier.issn | 0143-3334 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/104568 | - |
dc.description.abstract | Induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of breast cancers. We investigated the inhibitory effect of kalopanaxsaponin A (KPS-A) on cell invasion and MMP-9 activation in phorbol 12-myristate 13-acetate (PMA)-treated MCF-7 human breast cancer cells. KPS-A inhibited PMA-induced cell proliferation and invasion. PMA-induced cell invasion was blocked in the presence of a primary antibody of MMP-9, and KPS-A suppressed the increased expression and/or secretion of MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-1. Using specific inhibitors, we confirmed that PMA-induced cell invasion and MMP-9 expression is primarily regulated by nuclear factor-kappa B (NF-kappaB) activation via phosphatidylinositol 3-kinase (PI3K)/Akt and activator protein-1 (AP-1) activation via extracellular signal-regulated kinase (ERK)1/2. KPS-A decreased PMA-induced transcriptional activation of NF-kappaB and AP-1 and inhibited PMA-induced phosphorylation of ERK1/2 and Akt. Treatment with the protein kinase C (PKC)delta inhibitor rottlerin caused a marked decrease in PMA-induced MMP-9 secretion and cell invasion, as well as ERK/AP-1 activation, and KPS-A reduced PMA-induced membrane localization of PKCdelta. Furthermore, oral administration of KPS-A led to a substantial decrease in tumor volume and expression of proliferating cell nuclear antigen, MMP-9, TIMP-1 and PKCdelta in mice with MCF-7 breast cancer xenografts in the presence of 17beta-estradiol. These results suggest that KPS-A inhibits PMA-induced invasion by reducing MMP-9 activation, mainly via the PI3K/Akt/NF-kappaB and PKCdelta/ERK/AP-1 pathways in MCF-7 cells and blocks tumor growth and MMP-9-mediated invasiveness in mice with breast carcinoma. Therefore, KPS-A may be a promising anti-invasive agent with the advantage of oral dosing | - |
dc.description.statementOfResponsibility | open | - |
dc.format.extent | 1225~1233 | - |
dc.relation.isPartOf | CARCINOGENESIS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Acetophenones/pharmacology | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Antineoplastic Agents, Phytogenic/pharmacology* | - |
dc.subject.MESH | Antineoplastic Agents, Phytogenic/therapeutic use | - |
dc.subject.MESH | Benzopyrans/pharmacology | - |
dc.subject.MESH | Breast Neoplasms/chemically induced | - |
dc.subject.MESH | Breast Neoplasms/pathology | - |
dc.subject.MESH | Breast Neoplasms/prevention & control* | - |
dc.subject.MESH | Cell Line, Tumor | - |
dc.subject.MESH | Cell Proliferation/drug effects | - |
dc.subject.MESH | Extracellular Signal-Regulated MAP Kinases/metabolism | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Matrix Metalloproteinase 9/metabolism* | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred BALB C | - |
dc.subject.MESH | NF-kappa B/antagonists & inhibitors | - |
dc.subject.MESH | NF-kappa B/metabolism | - |
dc.subject.MESH | Neoplasm Invasiveness | - |
dc.subject.MESH | Neoplasm Transplantation | - |
dc.subject.MESH | Oleanolic Acid/analogs & derivatives* | - |
dc.subject.MESH | Oleanolic Acid/pharmacology | - |
dc.subject.MESH | Oleanolic Acid/therapeutic use | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/antagonists & inhibitors | - |
dc.subject.MESH | Phosphatidylinositol 3-Kinases/physiology* | - |
dc.subject.MESH | Protein Kinase C-delta/antagonists & inhibitors | - |
dc.subject.MESH | Protein Kinase C-delta/metabolism* | - |
dc.subject.MESH | Proto-Oncogene Proteins c-akt/physiology* | - |
dc.subject.MESH | Saponins/pharmacology* | - |
dc.subject.MESH | Saponins/therapeutic use | - |
dc.subject.MESH | Signal Transduction | - |
dc.subject.MESH | Tetradecanoylphorbol Acetate | - |
dc.subject.MESH | Transcription Factor AP-1/metabolism | - |
dc.subject.MESH | Transplantation, Heterologous | - |
dc.title | Kalopanaxsaponin A inhibits PMA-induced invasion by reducing matrix metalloproteinase-9 via PI3K/Akt- and PKCdelta-mediated signaling in MCF-7 human breast cancer cells | - |
dc.type | Article | - |
dc.contributor.college | College of Dentistry (치과대학) | - |
dc.contributor.department | Dept. of Oral Biology (구강생물학) | - |
dc.contributor.googleauthor | Sun Kyu Park | - |
dc.contributor.googleauthor | Young Sun Hwang | - |
dc.contributor.googleauthor | Kwang-Kyun Park | - |
dc.contributor.googleauthor | Hee-Juhn Park | - |
dc.contributor.googleauthor | Jeong Yeon Seo | - |
dc.contributor.googleauthor | Won-Yoon Chung | - |
dc.identifier.doi | 10.1093/carcin/bgp111 | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01429 | - |
dc.contributor.localId | A03676 | - |
dc.contributor.localId | A04472 | - |
dc.relation.journalcode | J00456 | - |
dc.identifier.eissn | 1460-2180 | - |
dc.identifier.pmid | 19420016 | - |
dc.contributor.alternativeName | Park, Kwang Kyun | - |
dc.contributor.alternativeName | Chung, Won Yoon | - |
dc.contributor.alternativeName | Hwang, Young Sun | - |
dc.contributor.affiliatedAuthor | Park, Kwang Kyun | - |
dc.contributor.affiliatedAuthor | Chung, Won Yoon | - |
dc.contributor.affiliatedAuthor | Hwang, Young Sun | - |
dc.citation.volume | 30 | - |
dc.citation.number | 7 | - |
dc.citation.startPage | 1225 | - |
dc.citation.endPage | 1233 | - |
dc.identifier.bibliographicCitation | CARCINOGENESIS, Vol.30(7) : 1225-1233, 2009 | - |
dc.identifier.rimsid | 51118 | - |
dc.type.rims | ART | - |
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