title: Curcumin suppresses the TPA-induced invasion through inhibition of PKCα-dependent MMP-expression in MCF-7 human breast cancer cells.
abstract: Curcumin (diferuloylmethane) is a polyphenol derived from the plant turmeric (Curcuma longa), which is commonly used as a spice. Although anti-carcinogenic, anti-oxidant, anti-inflammation, and anti-angiogenic properties have been reported, the effect of curcumin on breast cancer metastasis is unknown. Matrix metalloproteinase-9 (MMP-9) is a major component in cancer cell invasion. In this study, we investigated the inhibitory effect of curcumin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion and the molecular mechanisms involved in MCF-7 cells. Our results showed that curcumin inhibits TPA-induced MMP-9 expression and cell invasion through suppressing NF-κB and AP-1 activation. Also, curcumin strongly repressed the TPA-induced phosphorylation of p38 and JNK 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 curcumin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB/AP-1 pathway in MCF-7 cells. Curcumin may have potential value in restricting breast cancer metastasis.
authors.affiliation: Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, Jeonju 560-182, South Korea.
authors.forename: Jeong-Mi
authors.initials: JM
authors.lastname: Kim
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Noh
authors.forename: Kang-Beam
authors.initials: KB
authors.lastname: Kwon
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Yong-Ouk
authors.initials: YO
authors.lastname: You
authors.forename: Jin-Ki
authors.initials: JK
authors.lastname: Hwang
authors.forename: Bo-Mi
authors.initials: BM
authors.lastname: Hwang
authors.forename: Byeong-Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Sung-Hoo
authors.initials: SH
authors.lastname: Lee
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Sung Hoo
authors.initials: SH
authors.lastname: Jung
authors.forename: Hyun Jo
authors.initials: HJ
authors.lastname: Youn
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D061986:MCF-7 Cells; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000517:prevention & control; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D051571:Protein Kinase C-alpha; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D003474:Curcumin; D013755:Tetradecanoylphorbol Acetate