Decursin prevents TPA-induced invasion through suppression of PKCα/p38/NF-κB-dependent MMP-9 expression in MCF-7 human breast carcinoma cells.

Abstract

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-κB. Furthermore, decursin repressed the TPA-induced phosphorylation of p38 MAPK 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 decursin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB pathways in MCF-7 cells. Thus, decursin may have potential value in restricting breast cancer metastasis.

• Authors: Jeong-Mi Kim, Eun-Mi Noh, Mi-Seong Kim, Jin-Ki Hwang, Hong-Yeon Hwang, Do-Gon Ryu, Hye-Jung Kim, Hong-Nu Yu, Yong-Ouk You, Jong-Suk Kim, Hyun Jo Youn, Kang-Beom Kwon, Sung Hoo Jung, Young-Rae Lee
• Journal: International journal of oncology (Int J Oncol) Vol. 44 Issue 5 Pg. 1607-13 (May 2014) ISSN: 1791-2423 [Electronic] Greece
• PMID: 24604087 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzopyrans
• Butyrates
• Carcinogens
• decursin
• MMP9 protein, human
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate

Topics

• Benzopyrans (pharmacology)
• Breast Neoplasms (pathology)
• Butyrates (pharmacology)
• Carcinogens (pharmacology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Neoplasm Invasiveness (pathology)
• Signal Transduction (drug effects)
• Tetradecanoylphorbol Acetate (pharmacology)