Silibinin suppresses human osteosarcoma MG-63 cell invasion by inhibiting the ERK-dependent c-Jun/AP-1 induction of MMP-2.

Abstract

Silibinin is a natural flavonoid antioxidant with anti-hepatotoxic properties and pleiotropic anticancer capabilities. We tested the hypothesis that silibinin inhibits cellular invasiveness by down-regulating the focal adhesion kinase (FAK) and extracellular signal-regulated protein kinase (ERK)-dependent c-Jun/activator protein-1 (AP-1) induction, which leads to inhibition of urokinase-type plasminogen activator (u-PA) and matrix metalloproteinase-2 (MMP-2) expressions in human osteosarcoma MG-63 cells. We found that silibinin decreased cell adhesion and invasiveness, as well as inhibited u-PA and MMP-2 expressions. Silibinin reduced ERK 1/2 phosphorylation, but had no effects on the phosphorylation of c-Jun N-terminal kinases (JNKs) 1/2, p38 and Akt. Silibinin suppressed AP-1-binding activity and c-Jun levels and its phosphorylation without changes of c-Fos and Ets-1 levels. Silibinin also inhibited interleukin-6-induced ERK 1/2 and c-Jun phosphorylation, and cell invasiveness. Thus, silibinin may possess an anti-metastatic activity in MG-63 cells.

• Authors: Yih-Shou Hsieh, Shu-Chen Chu, Shun-Fa Yang, Pei-Ni Chen, Yu-Chuan Liu, Ko-Hsiu Lu
• Journal: Carcinogenesis (Carcinogenesis) Vol. 28 Issue 5 Pg. 977-87 (May 2007) ISSN: 0143-3334 [Print] England
• PMID: 17116726 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-jun
• Silymarin
• Transcription Factor AP-1
• Silybin
• Focal Adhesion Kinase 1
• PTK2 protein, human
• Extracellular Signal-Regulated MAP Kinases
• Urokinase-Type Plasminogen Activator
• Matrix Metalloproteinase 2

Topics

• Bone Neoplasms (metabolism, pathology)
• Cell Adhesion
• Cell Line, Tumor
• Cell Shape (drug effects)
• Cell Survival (drug effects)
• Disease Progression
• Extracellular Signal-Regulated MAP Kinases (pharmacology)
• Focal Adhesion Kinase 1 (metabolism)
• Humans
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Neoplasm Invasiveness
• Osteosarcoma (metabolism, pathology)
• Proto-Oncogene Proteins c-jun (pharmacology)
• Signal Transduction (drug effects)
• Silybin
• Silymarin (pharmacology)
• Transcription Factor AP-1 (pharmacology)
• Urokinase-Type Plasminogen Activator (metabolism)