Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2.
Berberine, a compound isolated from medicinal herbs, has been reported with many pharmacological effects related to anti-cancer and anti-inflammation capabilities. In this study, we observed that berberine exerted a dose- and time-dependent inhibitory effect on the motility and invasion ability of a highly metastatic A549 cells under non-cytotoxic concentrations. In cancer cell migration and invasion process, matrix-degrading proteinases are required. A549 cell treated with berberine at various concentrations showed reduced ECM proteinases including matrix metalloproteinase-2 (MMP2) and urokinase-plasminogen activator (u-PA) by gelatin and casein zymography analysis. The inhibitory effect is likely to be at the transcriptional level, since the reduction in the transcripts levels was corresponding to the proteins. Moreover, berberine also exerted its action via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). The upstream mediators of the effect involved c-jun, c-fos and NF-kappaB, as evidenced by reduced phosphorylation of the proteins. These findings suggest that berberine possesses an anti-metastatic effect in non-small lung cancer cell and may, therefore, be helpful in clinical treatment.
Peng
Pei-Ling
PL
Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, No 110, section 2, Chien Kauo N. Road, Taichung 402, Taiwan, ROC.
Hsieh
Yih-Shou
YS
Wang
Chau-Jong
CJ
Hsu
Jui-Ling
JL
Chou
Fen-Pi
FP
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000972:Antineoplastic Agents, Phytogenic; D061965:Matrix Metalloproteinase Inhibitors; D001599:Berberine; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9