Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2.
Cancer metastasis, involving multiple processes and various cytophysiological changes, is a primary cause of cancer death and may complicate the clinical management, even lead to death. Silibinin is a flavonoid antioxidant and wildly used for its antihepatotoxic properties and recent studies have revealed pleiotropic anticancer and antiproliferative capabilities of silibinin. In this study, we first observed that silibinin exerted a dose- and time-dependent inhibitory effect on the invasion and motility, but hardly on the adhesion, of highly metastatic A549 cells in the absence of cytotoxicity. To look at the precise involvement of silibinin in cancer metastasis, A549 cells were treated with silibinin at various concentrations, up to 100 microM, for a defined period and then subjected to gelatin zymography, casein zymography and Western blot to investigate the impacts of silibinin on metalloproteinase-2 (MMP-2), urokinase plasminogen activator (u-PA), and tissue inhibitor of metalloproteinase-2 (TIMP-2), respectively. The results showed that a silibinin treatment may decrease the expressions of MMP-2 and u-PA in a concentration- and time-dependent manner and enhance the expression of TIMP-2. Further analysis with semi-quantitative RT-PCR showed that silibinin may regulate the expressions of MMP-2 and u-PA on the transcriptional level while on the translational or post-translational level for TIMP-2.
Chu
Shu-Chen
SC
Department of Food Science, Chungtai Institute of Health Sciences and Technology, Taichung, Taiwan.
Chiou
Hui-Ling
HL
Chen
Pei-Ni
PN
Yang
Shun-Fa
SF
Hsieh
Yih-Shou
YS
D000970:Antineoplastic Agents / Q000378:metabolism; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020944:Silybum marianum; D009361:Neoplasm Invasiveness / Q000473:pathology; D010960:Plasminogen Activators / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000970:Antineoplastic Agents; D012838:Silymarin; D019716:Tissue Inhibitor of Metalloproteinase-2; D000077385:Silybin; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2