3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea inhibits tumor cell invasion by regulating protein kinase C-delta-dependent matrix metalloproteinase-9 expression

Title
3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea inhibits tumor cell invasion by regulating protein kinase C-delta-dependent matrix metalloproteinase-9 expression
Author(s)
황용필[황용필]윤효정[윤효정]최재호[최재호]천효곤[천효곤]정영철[정영철]김상겸[김상겸]김봉희[김봉희]권광일[권광일]정태천이광열[이광열]정혜광[정혜광]
Keywords
NF-KAPPA-B; MATRIX-METALLOPROTEINASE INHIBITORS; SMOOTH-MUSCLE-CELLS; HUMAN BREAST-CANCER; P38 MAPK; TRANSCRIPTION FACTORS; MMP-2 EXPRESSION; DRUG DEVELOPMENT; GENE-EXPRESSION; MESANGIAL CELLS
Issue Date
201010
Publisher
ELSEVIER IRELAND LTD
Citation
TOXICOLOGY LETTERS, v.198, no.2, pp.200 - 209
Abstract
In this study, we determined the effects of a novel chlorogenic acid, 3-caffeoyl, 4-dicaffeoylquinic acid (CDCQ) isolated from Salicornia herbacea, on tumor invasion and migration in human fibrosarcoma HT-1080 cells and investigated the possible mechanism(s) involved. CDCQ reduced the phorbol myristate acetate (PMA)-induced activation of matrix metalloproteinase (MMP)-9 and MMP-2 and inhibited cell invasion and migration. CDCQ suppressed PMA-induced expression of MMP-9 mRNA and protein by suppressing the transcription factor AP-1, without changing the level of tissue inhibitor of metalloproteinase (TIMP)-1. CDCQ-inhibited PMA-induced MMP-2 expression by suppressing membrane-type 1 MMP (MT1-MMP), but did not alter the TIMP-2 level. CDCQ also inhibited the PMA-induced nuclear translocation of c-Jun and c-Fos, which are upstream of PMA-induced MMP-9 expression. Furthermore, CDCQ strongly repressed PMA-induced phosphorylation of ERK, p38 MAPK, and JNK, which are dependent on the PKC delta pathway. In conclusion, we demonstrated that the anti-invasive effects of CDCQ occur through the inhibition of AP-1 and signaling pathways involving PKC delta and three MAPKs, leading to the downregulation of MMP-9 expression. Thus, CDCQ is an effective anti-metastatic agent that functions by downregulating MMP-9 gene expression. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/23482http://dx.doi.org/10.1016/j.toxlet.2010.06.018
ISSN
0378-4274
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약학대학 > 약학부 > Articles
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