Curcumin, a potential inhibitor of MMP-2 in human laryngeal squamous carcinoma cells HEp2

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.