Curcumin, a potential inhibitor of MMP-2 in human laryngeal squamous carcinoma cells HEp2.
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 microM) 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.
Mitra
Aparna
A
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India.
Chakrabarti
Jayati
J
Banerji
Aniruddha
A
Chatterjee
Amitava
A
Das
B R
BR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D016023:Integrins; D061965:Matrix Metalloproteinase Inhibitors; D021122:Protein Subunits; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14; D003474:Curcumin