Silibinin prevents TPA-induced MMP-9 expression by down-regulation of COX-2 in human breast cancer cells.
BACKGROUND
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.


OBJECTIVE
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 (MEK 1/2 inhibitor).


CONCLUSIONS
Silibinin down-regulates TPA-induced MMP-9 expression through inhibition of COX-2 expression in breast cancer cells.
Kim
Sangmin
S
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-gu, Seoul 135-710, South Korea.
Kim
Sung Hoon
SH
Hur
Sung Mo
SM
Lee
Se-Kyung
SK
Kim
Wan Wook
WW
Kim
Jee Soo
JS
Kim
Jung-Han
JH
Choe
Jun-Ho
JH
Nam
Seok Jin
SJ
Lee
Jeong Eon
JE
Yang
Jung-Hyun
JH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020944:Silybum marianum / Q000737:chemistry*; D009570:Nitriles / Q000494:pharmacology; D008517:Phytotherapy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012639:Seeds; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D002070:Butadienes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D012838:Silymarin; D013449:Sulfonamides; C113580:U 0126; D000077385:Silybin; D051546:Cyclooxygenase 2; D020930:MAP Kinase Kinase Kinases; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D000068579:Celecoxib; D013755:Tetradecanoylphorbol Acetate