Cordycepin inhibits TPA-induced matrix metalloproteinase-9 expression by suppressing the MAPK/AP-1 pathway in MCF-7 human breast cancer cells

Abstract

Abstract. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix (ECM), plays an important role in breast cancer cell invasion. NF-κB and AP-1 are known to induce MMP-9 expression. We investigated whether cordycepin, an NF-κB 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-κB 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.

Potential of Topical Microemulsion Serum Formulations to Enhance In Vitro and Clinical Anti-Skin Wrinkle Benefits of Cordyceps Militaris Extracts

“…On the other hand, cordycepin was noted as a major component of CW which responsible for MMP-1 and elastase inhibition since it exhibited potent MMP-1 and elastase inhibitory activities with the inhibition of 58.5 ± 4.9% and 76.5 ± 7.1%, respectively. Although, there are some previous reports revealed about the MMP-1 inhibitory activity of C. militaris, they suggested cordycepin as the key compound that inhibited the activator protein-1 and resulting in the suppression of MMP-1 expression [20,21]. However, the present study was the rst to remarked that both cordycepin and C. militaris extracts exerted a direct effect on the MMP-1 enzyme.…”