Silibinin suppresses PMA-induced MMP-9 expression by blocking the AP-1 activation via MAPK signaling pathways in MCF-7 human breast carcinoma cells

• Published in: Biochemical and biophysical research communications 2007-03, Vol.354 (1), p.165-171
• Main Authors: Lee, Syng-Ook, Jeong, Yun-Jeong, Im, Hyo Gwon, Kim, Cheorl-Ho, Chang, Young-Chae, Lee, In-Seon
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - metabolism; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Combinations; Humans; Invasion; MAP Kinase Signaling System - drug effects; Matrix Metalloproteinase 9 - metabolism; MCF-7 human breast carcinoma cells; Milk thistle; MMP-9; PMA; Silibinin; Silybum marianum; Silymarin - administration & dosage; Tetradecanoylphorbol Acetate - administration & dosage; Transcription Factor AP-1 - metabolism; Transcriptional Activation - drug effects
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2006.12.181

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.