Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells.
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.
Noh
Eun-Mi
EM
Department of Biochemistry and Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 560-182, Korea.
Youn
Hyun Jo
HJ
Jung
Sung Hoo
SH
Han
Ji-Hey
JH
Jeong
Youg-Ju
YJ
Chung
Eun-Yong
EY
Jung
Ji-Youn
JY
Kim
Byeong-Soo
BS
Lee
Sung-Ho
SH
Lee
Young-Rae
YR
Kim
Jong-Suk
JS
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
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