Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2

• Published in: Toxicology and applied pharmacology Vol. 214; no. 1; pp. 8 - 15
• Main Authors: Peng, Pei-Ling, Hsieh, Yih-Shou, Wang, Chau-Jong, Hsu, Jui-Ling, Chou, Fen-Pi
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01-07-2006; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Antineoplastic Agents, Phytogenic - pharmacology; Berberine; Berberine - pharmacology; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - pathology; CASEIN; Cell Line, Tumor; Cell Movement - drug effects; Dose-Response Relationship, Drug; GELATIN; HERBS; Humans; INFLAMMATION; Lung cancer; Lung Neoplasms - pathology; LUNGS; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase Inhibitors; Medical sciences; METASTASES; MMP2; Neoplasm Invasiveness; NEOPLASMS; PHOSPHORYLATION; PLASMINOGEN; Pneumology; Reverse Transcriptase Polymerase Chain Reaction; TIME DEPENDENCE; Time Factors; TIMP-2; Tissue Inhibitor of Metalloproteinase-2 - biosynthesis; Toxicology; Tumors of the respiratory system and mediastinum; u-PA; UROKINASE; Urokinase-Type Plasminogen Activator - antagonists & inhibitors; Urokinase-Type Plasminogen Activator - biosynthesis; Berberine; TIMP-2; u-PA; MMP2; Lung cancer; Human; Lung disease; u-Plasminogen activator; Serine endopeptidases; Respiratory disease; Enzyme; Tissue inhibitor metalloproteinase 2; Antidiarrheal agent; Metalloendopeptidases; Malignant tumor; Bronchopulmonary; Invasion; Gelatinase A; Peptidases; Alkaloid; Bronchus disease; Hydrolases; Tumor cell
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2005.11.010

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-κB, 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.