Abstract
Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and 40 μM for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.
Highlights
Breast cancer is the most common leading cause of death among women worldwide (Kohrmann et al, 2009) due to distant metastases
At high concentrations of curcumin, tissue inhibitor of matrix metalloproteinases (TIMP)-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of Matrix Metalloproteinase (MMP)-2 and matrix metalloproteinase-9 (MMP-9) gene expression levels in a concentration- and time-dependent manner
These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting matrix metalloproteinase-2 (MMP-2) and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells
Summary
Breast cancer is the most common leading cause of death among women worldwide (Kohrmann et al, 2009) due to distant metastases. Tumor cells produce Matrix Metalloproteinase (MMP) enzymes that destroy the basement of membranes, permitting invasion (Kohrmann et al, 2009). MMP is a family of 23 members structurally and functionally related endopeptidases (Nagase et al, 2006). MMPs are upregulated in most human tumor cell lines and their high levels are linked to metastasis (Baker et al, 2000). The stage of tumor progression is positively correlated with the expression of MMP family members (MMP-1, 2, 3, 7, 9, 11, and 14) (Overall and Lopez-Otin, 2002). MMP-2 and MMP-9 help in forming neovascularization and are involved in tumor angiogenesis mainly through their matrix-degrading capacity (John and Tuszynski, 2001). MMP-9 up-regulation was associated with a shortened relapse-free survival in breast cancer patients (Vizoso et al, 2007)
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