1. Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells
- Author
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Kim, Sangmin, Kim, Sung Hoon, Hur, Sung Mo, Lee, Se-Kyung, Kim, Wan Wook, Kim, Jee Soo, Kim, Jung-Han, Choe, Jun-Ho, Nam, Seok Jin, Lee, Jeong Eon, and Yang, Jung-Hyun
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MILK thistle , *BREAST cancer diagnosis , *METALLOPROTEINASES , *CYCLOOXYGENASE 2 inhibitors , *CELECOXIB , *CARCINOGENESIS - Abstract
Abstract: Ethnopharmacological relevance: The expression of matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2) are pivotal steps in breast cancer pathogenesis. In a previous study, we reported that silibinin suppresses TPA-induced MMP-9 expression through the Raf/MEK/ERK pathway. Aims of the study: Herein we determined the co-relationship between MMP-9 and COX-2, as well as the effect of silibinin on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 and COX-2 expression in the human breast cancer cells, MCF-7 and MDA-MB231. Methods: The toxicity of silibinin was evaluated by Quick Cell Proliferation Assay Kit II. MMP-9 and COX-2 expression were analyzed by Zymography and Western blotting, respectively. Adenoviral constitutively active (CA)-MEK was used to activate MEK/ERK pathway. Results: The expression of MMP-9 and COX-2 in response to TPA was increased, whereas TPA-induced MMP-9 and COX-2 expression was decreased by silibinin. Our results showed that TPA-induced MMP-9 expression was inhibited by celecoxib in a dose-dependent fashion, but not MMP-1-expression. Both MMP-9 and COX-2 expression were significantly increased by CA-MEK overexpression. In contrast, TPA-induced MMP-9 and COX-2 expression was decreased by UO126 (MEK1/2 inhibitor). Conclusion: Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells. [Copyright &y& Elsevier]
- Published
- 2009
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