title: Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells.
abstract: Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in breast cancer cell invasion. NF-kappaB and AP-1 are known to induce MMP-9 expression. We investigated whether cordycepin, an NF-kappaB or AP-1 inhibitor, can modulate MMP-9 expression and cell invasion in MCF-7 cells. Toxicity of cordycepin was determined by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MMP-9 expression was determined by real-time PCR, Zymography, and Western blot analysis. AP-1 activation was assayed by electrophoretic mobility shift assay (EMSA). MAPK signaling was evaluated by Western blotting with specific p-ERK, and ERK, p-p38, p38, p-JNK, JNK antibodies. Cordycepin suppressed AP-1 activation, but not NF-kappaB activation in 12-O-tetradecanoylpho-bol-13-acetate (TPA)-treated MCF-7 cells. Cordycepin inhibits TPA-induced MMP-9 expression and cell invasion by suppressing AP-1 activation. Also, cordycepin suppressed the MAPK signaling pathway. Cordycepin is a potent inhibitor of TPA-induced MMP-9 expression and blocks strongly the ability of AP-1 activation via MAPK signaling pathway in MCF-7 cells.
authors.affiliation: Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 560-182, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Noh
authors.forename: Hyun Jo
authors.initials: HJ
authors.lastname: Youn
authors.forename: Sung Hoo
authors.initials: SH
authors.lastname: Jung
authors.forename: Ji-Hey
authors.initials: JH
authors.lastname: Han
authors.forename: Youg-Ju
authors.initials: YJ
authors.lastname: Jeong
authors.forename: Eun-Yong
authors.initials: EY
authors.lastname: Chung
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Jung
authors.forename: Byeong-Soo
authors.initials: BS
authors.lastname: Kim
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Young-Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Jong-Suk
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003839:Deoxyadenosines / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D020780:Matrix Metalloproteinase 9; C058120:cordycepin; D013755:Tetradecanoylphorbol Acetate