title: 3-Caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea inhibits tumor cell invasion by regulating protein kinase C-delta-dependent matrix metalloproteinase-9 expression.
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 PKCdelta pathway. In conclusion, we demonstrated that the anti-invasive effects of CDCQ occur through the inhibition of AP-1 and signaling pathways involving PKCdelta 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.
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea; College of Pharmacy, Chonnam National University, Gwangju, South Korea.
authors.forename: Yong Pil
authors.initials: YP
authors.lastname: Hwang
authors.forename: Hyo Jeong
authors.initials: HJ
authors.lastname: Yun
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Choi
authors.forename: Hyo Kon
authors.initials: HK
authors.lastname: Chun
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Chung
authors.forename: Sang Kyum
authors.initials: SK
authors.lastname: Kim
authors.forename: Bong-Hee
authors.initials: BH
authors.lastname: Kim
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Kwon
authors.forename: Tae Cheon
authors.initials: TC
authors.lastname: Jeong
authors.forename: Kwang Youl
authors.initials: KY
authors.lastname: Lee
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019663:Chenopodiaceae / Q000737:chemistry*; D002726:Chlorogenic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D051745:Protein Kinase C-delta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C544671:3-caffeoyl-4-dihydrocaffeoylquinic acid; D000972:Antineoplastic Agents, Phytogenic; D002726:Chlorogenic Acid; D051745:Protein Kinase C-delta; D020780:Matrix Metalloproteinase 9