Decursin prevents TPA-induced invasion through suppression of PKC alpha/p38/NF-kappa B-dependent MMP-9 expression in MCF-7 human breast carcinoma cells

作者:Kim Jeong Mi; Noh Eun Mi; Kim Mi Seong; Hwang Jin Ki; Hwang Hong Yeon; Ryu Do Gon; Kim Hye Jung; Yu Hong Nu; You Yong Ouk; Kim Jong Suk; Youn Hyun Jo; Kwon Kang Beom; Jung Sung Hoo*; Lee Young Rae
来源:International Journal of Oncology, 2014, 44(5): 1607-1613.
DOI:10.3892/ijo.2014.2327

摘要

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-kappa B. Furthermore, decursin repressed the TPA-induced phosphorylation of p38 MAPK and inhibited TPA-induced translocation of PKC alpha from the cytosol to the membrane, but did not affect the translocation of PKC delta. These results indicate that decursin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKC alpha, MAPK and NF-kappa B pathways in MCF-7 cells. Thus, decursin may have potential value in restricting breast cancer metastasis.