Isoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression=이소징게틴 PI3K/AKT의존적 MMP-9발현조절에 의한 암세포 침윤억제

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dc.contributor.authorS O Yoon-
dc.contributor.authorS Shin-
dc.contributor.authorHo Jae Lee-
dc.contributor.authorHyo Kon Chun-
dc.contributor.authorA S Chung-
dc.date.accessioned2017-04-19T09:05:35Z-
dc.date.available2017-04-19T09:05:35Z-
dc.date.issued2006-
dc.identifier.issn1535-7163-
dc.identifier.uri10.1158/1535-7163.MCT-06-0321ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/7678-
dc.description.abstractMatrix metalloproteinase (MMP)-9 plays a key role in tumor invasion. Inhibitors of MMP-9 were screened from Metasequoia glyptostroboides (Dawn redwood) and one potent inhibitor, isoginkgetin, a biflavonoid, was identified. Noncytotoxic levels of isoginkgetin decreased MMP-9 production profoundly, but up-regulated the level of tissue inhibitor of metalloproteinase (TIMP)-1, an inhibitor of MMP-9, in HT1080 human fibrosarcoma cells. The major mechanism of Ras-dependent MMP-9 production in HT1080 cells was phosphatidylinositol 3-kinase (PI3K)/Akt/ nuclear factor-κB (NF-κB) activation. Expression of dominant-active H-Ras and p85 (a subunit of PI3K) increased MMP-9, activity, whereas dominant-negative forms of these molecules decreased the level of MMP-9. H-Ras did not increase MMP-9 in the presence of a PI3K inhibitor, LY294002, and a NF-κB inhibitor, SN50. Further studies showed that isoginkgetin regulated MMP-9 production via PI3K/Akt/ NF-κB pathway, as evidenced by the findings that isoginkgetin inhibited activities of both Akt and NF-κB. PI3K/Akt is a well-known key pathway for cell invasion, and isoginkgetin inhibited HT1080 tumor cell invasion substantially. Isoginkgetin was also quite effective in inhibiting the activities of Akt and MMP-9 in MDA-MB-231 breast carcinomas and B16F1O melanoma. Moreover, isoginkgetin treatment resulted in marked decrease in invasion of these cells. In summary, PI3K/ Akt is a major pathway for MMP-9 expression and isoginkgetin markedly decreased MMP-9 expression and invasion through inhibition of this pathway. This suggests that isoginkgetin could be a potential candidate as a therapeutic agent against tumor invasion.-
dc.publisherAmer Assoc Cancer Research-
dc.titleIsoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression=이소징게틴 PI3K/AKT의존적 MMP-9발현조절에 의한 암세포 침윤억제-
dc.title.alternativeIsoginkgetin inhibits tumor cell invasion by regulating phosphatidylinositol 3-kinase/Akt-dependent matrix metalloproteinase-9 expression-
dc.typeArticle-
dc.citation.titleMolecular Cancer Therapeutics-
dc.citation.number11-
dc.citation.endPage2675-
dc.citation.startPage2666-
dc.citation.volume5-
dc.contributor.affiliatedAuthorHo Jae Lee-
dc.contributor.affiliatedAuthorHyo Kon Chun-
dc.contributor.alternativeName윤상오-
dc.contributor.alternativeName신세정-
dc.contributor.alternativeName이호재-
dc.contributor.alternativeName전효곤-
dc.contributor.alternativeName정안식-
dc.identifier.bibliographicCitationMolecular Cancer Therapeutics, vol. 5, no. 11, pp. 2666-2675-
dc.identifier.doi10.1158/1535-7163.MCT-06-0321-
dc.description.journalClassY-
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Division of Bio Technology Innovation > SME Support Center > 1. Journal Articles
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