Silibinin Inhibits Invasion of Oral Cancer Cells by Suppressing the MAPK Pathway
- 1 March 2006
- journal article
- other
- Published by SAGE Publications in Journal of Dental Research
- Vol. 85 (3), 220-225
- https://doi.org/10.1177/154405910608500303
Abstract
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.Keywords
This publication has 22 references indexed in Scilit:
- Suppression of distant pulmonary metastasis of MDA-MB 435 human breast carcinoma established in mammary fat pads of nude mice by retroviral-mediated TIMP-2 gene transferThe Journal of Gene Medicine, 2004
- Silibinin Protects against Photocarcinogenesis via Modulation of Cell Cycle Regulators, Mitogen-Activated Protein Kinases, and Akt SignalingCancer Research, 2004
- A phase I and pharmacokinetic (PK) study of weekly docetaxel (D), cisplatin (P), and daily capecitabine (C) (DPC) in patients with advanced solid tumorsJournal of Clinical Oncology, 2004
- Silibinin inhibits the invasion of human lung cancer cells via decreased productions of urokinase‐plasminogen activator and matrix metalloproteinase‐2Molecular Carcinogenesis, 2004
- Silibinin upregulates the expression of cyclin-dependent kinase inhibitors and causes cell cycle arrest and apoptosis in human colon carcinoma HT-29 cellsOncogene, 2003
- Preparation and Pharmacological Evaluation of Silibinin LiposomesArzneimittelforschung, 2003
- Oral cavity and pharynx cancer incidence rates in the United States, 1975–1998 ☆ ☆Portions of this manuscript were presented at the meeting of the American Association of Public Health Dentistry in October 1999.Oral Oncology, 2002
- Expression of MMPS, MT-MMP, and TIMPs in squamous cell carcinoma of the oral cavity: Correlations with tumor invasion and metastasisHead & Neck, 1999
- Inhibitory effect of silymarin, an anti-hepatotoxic flavonoid, on 12-O-tetradecanoylphorbol-13-acetate-induced epidermal ornithine decarboxylase activity and mRNA in SENCAR miceCarcinogenesis: Integrative Cancer Research, 1994
- Metastatic potential correlates with enzymatic degradation of basement membrane collagenNature, 1980