Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells

Chiao-Wen Lin; Pei-Ni Chen; Mu-Kuan Chen; Wei-En Yang; Chih-Hsin Tang; Shun-Fa Yang; Yih-Shou Hsieh

doi:10.1371/journal.pone.0080883

Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells

PLoS One. 2013 Nov 20;8(11):e80883. doi: 10.1371/journal.pone.0080883. eCollection 2013.

Authors

Chiao-Wen Lin¹, Pei-Ni Chen, Mu-Kuan Chen, Wei-En Yang, Chih-Hsin Tang, Shun-Fa Yang, Yih-Shou Hsieh

Affiliation

¹ Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan ; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.

Abstract

Background: Kaempferol has been proposed as a potential drug for cancer chemoprevention and treatment because it is a natural polyphenol contained in plant-based foods. Recent studies have demonstrated that kaempferol protects against cardiovascular disease and cancer. Based on this finding, we investigated the mechanisms by which kaempferol produces the anti-metastatic effect in human tongue squamous cell carcinoma SCC4 cells.

Methodology/principal findings: In this study, we provided molecular evidence associated with the anti-metastatic effect of kaempferol by demonstrating a substantial suppression of SCC4 cell migration and invasion. This effect was associated with reduced expressions of MMP-2 and TIMP-2 mRNA and protein levels. Analysis of the transcriptional regulation indicated that kaempferol inhibited MMP-2 transcription by suppressing c-Jun activity. Kaempferol also produced an inhibitory effect on the phosphorylation of ERK1/2.

Conclusions: These findings provide new insights into the molecular mechanisms involved in the anti-metastatic effect of kaempferol, and are valuable in the prevention of oral cancer metastasis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Butadienes / pharmacology
Cell Line, Tumor
Cell Movement / drug effects
Cell Movement / genetics
Cell Survival / drug effects
Cell Survival / genetics
DNA, Neoplasm / metabolism
Down-Regulation / drug effects*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Expression Regulation, Neoplastic / drug effects
Humans
Kaempferols / pharmacology*
Matrix Metalloproteinase 2 / genetics*
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase Inhibitors / pharmacology
Mouth Neoplasms / enzymology*
Mouth Neoplasms / pathology
Neoplasm Invasiveness
Nitriles / pharmacology
Phosphorylation / drug effects
Protein Binding / drug effects
Protein Binding / genetics
RNA, Messenger / genetics
RNA, Messenger / metabolism
Signal Transduction / drug effects*
Signal Transduction / genetics
Tissue Inhibitor of Metalloproteinase-2 / metabolism
Transcription Factor AP-1 / metabolism*
Transcription, Genetic / drug effects

Substances

Butadienes
DNA, Neoplasm
Kaempferols
Matrix Metalloproteinase Inhibitors
Nitriles
RNA, Messenger
TIMP2 protein, human
Transcription Factor AP-1
U 0126
Tissue Inhibitor of Metalloproteinase-2
kaempferol
Extracellular Signal-Regulated MAP Kinases
Matrix Metalloproteinase 2

Grants and funding

This study was financially supported by grants from National Science Council, Taiwan (NSC-100-2632-B-040-001-MY3). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.