期刊
JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY
卷 25, 期 4, 页码 679-689出版社
BEGELL HOUSE INC
DOI: 10.1615/JEnvironPatholToxicolOncol.v25.i4.70
关键词
curcumin; FAK; integrin; invasion; MMP-2
类别
Curcurnin (diferuloylmethane) has been widely studied for its tumor inhibiting and anticarcinogenic properties. In the present communication, we studied the effect of curcumin on matrixmetalloproteinase-2 (MMP-2), integrin receptors, and focal adhesion kinase (FAK) in human laryngeal cancer cells, HEp2. Methods: HEp2 cells were treated with curcumin (5 mu M) for 30 days and then grown without curcumin for 28 days. Effect of curcumin on MMP-2 expression and activity and on membrane type matrixmetafloproteinase-1 (MT1-MMP), FAK, and integrin receptors was studied by zymography, Western blot, ELISA, RT-PCR, and cell adhesion assay. Results: Treatment of HEp2 cells with curcumin downregulated MMP-2 expression and activity and expression of integrin receptors, FAK, and MT1-MMP to almost background levels. MMP-2 (but not MMP-9) mRNA expression was abolished on curcurnin treatment, indicating specific inhibition of MMP-2. Invasive potential of HEp2 cells was also significantly reduced. After drug withdrawal, expression of MMP-2, integrin receptors, 1wrl-MMP, and FAK returned to control levels. However, MMP-2 activity in serum free medium remained low. Conclusions: Downregulation of integrin receptors and low levels of FAK may hinder integrinmediated signal transduction, preventing upregulation of MMP-2 activity. Reduction of MMP-2 activity and inhibition of HEp2 cell invasion by curcumin strongly indicate the potential of cutcurnin as an inhibitor of tumor cell invasion and metastasis.
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