Silibinin Inhibits Invasion of Oral Cancer Cells by Suppressing the MAPK Pathway

• Published in: Journal of dental research Vol. 85; no. 3; pp. 220 - 225
• Main Authors: Chen, P.-N., Hsieh, Y.-S., Chiang, C.-L., Chiou, H.-L., Yang, S.-F., Chu, S.-C.
• Format: Journal Article
• Language: English
• Published: United States SAGE Publications 01-03-2006; SAGE PUBLICATIONS, INC
• Subjects: Animals; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Cell Line, Tumor - drug effects; Dentistry; Humans; Male; MAP Kinase Signaling System - drug effects; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred C57BL; Neoplasm Invasiveness; Neoplasm Metastasis - prevention & control; Protease Inhibitors - pharmacology; Protease Inhibitors - therapeutic use; Silymarin - pharmacology; Silymarin - therapeutic use; Tongue Neoplasms - drug therapy; Tongue Neoplasms - metabolism; Urokinase-Type Plasminogen Activator - antagonists & inhibitors; Urokinase-Type Plasminogen Activator - biosynthesis; silibinin; invasion; MMP-2; u-PA
• ISSN: 0022-0345; 1544-0591
• DOI: 10.1177/154405910608500303

Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Here, we provide molecular evidence associated with the anti-metastatic effect of silibinin by showing a marked inhibition of the invasion and motility of SCC-4 tongue cancer cells, with 89% and 66.4% of inhibition, respectively, by 100 μM of silibinin. This effect was associated with a reduced expression of MMP-2 and u-PA, together with an enhanced expression of TIMP-2 and PAI-1. Silibinin also exerted an inhibitory effect on the phosphorylation of ERK1/2. Additionally, pre-treatment of SCC-4 cancer cells with 10 and 20 μM of U0126, a specific MEK inhibitor, resulted in a reduced expression of MMP-2 (18.7 and 51.4%) and u-PA (19.2 and 48.9%) concomitantly with a marked inhibition of cell invasion (13.7 and 45.7%). Finally, silibinin was evidenced by its inhibition of the metastasis of Lewis lung carcinoma (LLC) cells in vivo. These results suggested that silibinin can reduce the invasion and metastasis of tumor cells, and such a characteristic may be of great value in the development of a potential cancer therapy.