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Journal of Environmental Pathology, Toxicology and Oncology

ISSN for PRINT: 0731-8898

Institutional price:	$672.00
Issues per year:	4

Best Paper Award Selection - Editorial Board Site

2006, Volume25

94 pages

Issue price - $172.00

Curcumin, a Potential Inhibitor of MMP-2 in Human Laryngeal Squamous Carcinoma Cells HEp2

Aparna Mitra
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata-700 026, India

Jayati Chakrabarti
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata-700 026, India

Aniruddha Banerji
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata-700 026, India

Amitava Chatterjee
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata-700 026, India

B. R. Das
Research & Development Division, SRL Ranbaxy, Mumbai, India

ABSTRACT

Curcumin (diferuloylmethane) has been widely studied for its tumor inhibiting and anticarcino-genic properties. In the present communication, we studied the effect of curcumin on matrix-metalloproteinase-2 (MMP-2), integrin receptors, and focal adhesion kinase (FAK) in human laryngeal cancer cells, HEp2. Methods: HEp2 cells were treated with curcumin (5 μM) for 30 days and then grown without curcumin for 28 days. Effect of curcumin on MMP-2 expression and activity and on membrane type matrixmetalloproteinase-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 curcumin 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, MT1-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 integrin-mediated 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 curcumin as an inhibitor of tumor cell invasion and metastasis.