Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

Abstract

Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis.

• Authors: Eun-Mi Noh, Yeon-Ju Park, Jeong-Mi Kim, Mi-Seong Kim, Ha-Rim Kim, Hyun-Kyung Song, On-Yu Hong, Hong-Seob So, Sei-Hoon Yang, Jong-Suk Kim, Samg Hyun Park, Hyun-Jo Youn, Yong-Ouk You, Ki-Bang Choi, Kang-Beom Kwon, Young-Rae Lee
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 764 Pg. 79-86 (Oct 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 26101063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Flavonoids
• Flavonols
• NF-kappa B
• Reactive Oxygen Species
• DNA
• Protein Kinase C-alpha
• Mitogen-Activated Protein Kinases
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate
• fisetin

Topics

• Breast Neoplasms (pathology)
• Cell Membrane (drug effects, metabolism)
• DNA (metabolism)
• Enzyme Activation (drug effects)
• Flavonoids (pharmacology)
• Flavonols
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MAP Kinase Signaling System (drug effects)
• MCF-7 Cells
• Matrix Metalloproteinase 9 (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Neoplasm Invasiveness
• Protein Kinase C-alpha (metabolism)
• Protein Transport (drug effects)
• Reactive Oxygen Species (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)