Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells.
Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of silibinin, a flavonoid antioxidant from milk thistle (Silybum marianum L.) on PMA-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Silibinin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7. Silibinin has been found to inhibit PMA-induced MMP-9 gene transcriptional activity by blocking the activation of AP-1 via MAPK signaling pathways. Moreover, the Matrigel invasion assay showed that silibinin reduces PMA-induced invasion of MCF-7 cells. These results suggest that silibinin represents a potential anti-metastatic agent suppressing PMA-induced cancer cell invasion through the specific inhibition of AP-1-dependent MMP-9 gene expression.
Lee
Syng-Ook
SO
Department of Food Science and Technology and The Center for Traditional Microorganism Resources (TMR), Keimyung University, Daegu 704-701, Republic of Korea.
Jeong
Yun-Jeong
YJ
Im
Hyo Gwon
HG
Kim
Cheorl-Ho
CH
Chang
Young-Chae
YC
Lee
In-Seon
IS
D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects*
D004338:Drug Combinations; D012838:Silymarin; D018808:Transcription Factor AP-1; D000077385:Silybin; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate