title: Decursin prevents TPA-induced invasion through suppression of PKCα/p38/NF-κB-dependent MMP-9 expression in MCF-7 human breast carcinoma cells.
abstract: Decursin, a coumarin compound, was first isolated from the roots of Angelica gigas almost four decades ago. It was found to exhibit cytotoxicity against various human cancer cells and to possess anti-amnesic activity in vivo through the inhibition of AChE activity. However, the effect of decursin on breast cancer invasion is unknown. Matrix metalloproteinase-9 (MMP-9) is known to be an important factor for cancer cell invasion. Therefore, in this study, we investigated the inhibitory effect of decursin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. Our results showed that decursin inhibits TPA-induced MMP-9 expression and cell invasion through the suppression of NF-κB. Furthermore, decursin repressed the TPA-induced phosphorylation of p38 MAPK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane, but did not affect the translocation of PKCδ. These results indicate that decursin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB pathways in MCF-7 cells. Thus, decursin may have potential value in restricting breast cancer metastasis.
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Jeong-Mi
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Noh
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Mi-Seong
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Hwang
authors.affiliation: Department of Korean Physiology, School of Korean Medicine, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Hong-Yeon
authors.initials: HY
authors.lastname: Hwang
authors.affiliation: Department of Korean Physiology, School of Korean Medicine, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Do-Gon
authors.initials: DG
authors.lastname: Ryu
authors.affiliation: Department of Family Medicine, The Catholic University of Korea, Incheon St. Mary's Hospital, Bupyeong-gu, Incheon 403-720, Republic of Korea.
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Medical Oncology, Xin Hua Hospital Affiliated to Dalian University, Dalian 116021, P.R. China.
authors.forename: Hong-Nu
authors.initials: HN
authors.lastname: Yu
authors.affiliation: Department of Oral Biochemistry, and Institute of Biomaterials - Implant, School of Dentistry, Wonkwang University, Iksan 570-749, Republic of Korea.
authors.forename: Yong-Ouk
authors.initials: YO
authors.lastname: You
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Division of Breast and Thyroid Surgery, Department of Surgery, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Hyun Jo
authors.initials: HJ
authors.lastname: Youn
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Kang-Beom
authors.initials: KB
authors.lastname: Kwon
authors.affiliation: Division of Breast and Thyroid Surgery, Department of Surgery, Chonbuk National University Medical School, Jeonju 560-182, Republic of Korea.
authors.forename: Sung Hoo
authors.initials: SH
authors.lastname: Jung
authors.affiliation: Center for Metabolic Function Regulation, Wonkwang University School of Medicine, Iksan 570-749, Republic of Korea.
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
mesh_terms: D001578:Benzopyrans / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002087:Butyrates / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D002087:Butyrates; D002273:Carcinogens; C101278:decursin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate