Silibinin suppresses human osteosarcoma MG-63 cell invasion by inhibiting the ERK-dependent c-Jun/AP-1 induction of MMP-2.
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.
Hsieh
Yih-Shou
YS
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan.
Chu
Shu-Chen
SC
Yang
Shun-Fa
SF
Chen
Pei-Ni
PN
Liu
Yu-Chuan
YC
Lu
Ko-Hsiu
KH
D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D048049:Extracellular Signal-Regulated MAP Kinases / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D016755:Proto-Oncogene Proteins c-jun / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D016755:Proto-Oncogene Proteins c-jun; D012838:Silymarin; D018808:Transcription Factor AP-1; D000077385:Silybin; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2