Resveratrol suppresses TPA-induced matrix metalloproteinase-9 expression through the inhibition of MAPK pathways in oral cancer cells.

Abstract

BACKGROUND:

Naturally occurring agents, such as resveratrol, have been determined to benefit health. Numerous studies have demonstrated that resveratrol has antioxidative, cardioprotective, and neuroprotective properties. However, the effect of resveratrol exerts on the metastasis of oral cancer cells remains unclear. In this study, we investigated the effect the anti-invasive activity of resveratrol on a human oral cancer cell line (SCC-9) in vitro and the underlying mechanisms.

METHODS:

Cell viability was examined by MTT assay, whereas cell motility was measured by migration and wound-healing assays. Zymography, reverse-transcriptase polymerase chain reaction (PCR), and promoter assays confirmed the inhibitory effects of resveratrol on matrix metalloproteinase-9 (MMP-9) expression in oral cancer cells.

RESULTS:

We established that various concentrations (0-100 μM) of resveratrol inhibited the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced migration capacities of SCC-9 cells and caused no cytotoxic effects. Zymography and Western blot analyses suggested that resveratrol inhibited TPA-induced MMP-9 gelatinolytic activity and protein expression. In addition, the results indicated that resveratrol inhibited the phosphorylation of c-Jun N-terminal kinase (JNK)1/2 and extracellular-signal-regulated kinase (ERK)1/2 involved in downregulating protein expression and the transcription of MMP-9.

CONCLUSION:

In summary, resveratrol inhibited MMP-9 expression and oral cancer cell metastasis by downregulating JNK1/2 and ERK1/2 signals pathways and, thus, exerts beneficial effects in chemoprevention.

• Authors: Feng-Yan Lin, Yi-Hsien Hsieh, Shun-Fa Yang, Chang-Tai Chen, Chih-Hsin Tang, Ming-Yung Chou, Yi-Ting Chuang, Chiao-Wen Lin, Mu-Kuan Chen
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 44 Issue 9 Pg. 699-706 (Oct 2015) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 25401496 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents, Phytogenic
• Stilbenes
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate
• Resveratrol

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Carcinoma, Squamous Cell (drug therapy, enzymology, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Down-Regulation (drug effects)
• Enzyme Activation (drug effects)
• Head and Neck Neoplasms (drug therapy, enzymology, metabolism, pathology)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Matrix Metalloproteinase 9 (biosynthesis)
• Mitogen-Activated Protein Kinase 1 (drug effects)
• Mitogen-Activated Protein Kinase 3 (drug effects)
• Mouth Neoplasms (drug therapy, enzymology, metabolism, pathology)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Resveratrol
• Signal Transduction (drug effects)
• Squamous Cell Carcinoma of Head and Neck
• Stilbenes (administration & dosage, metabolism, pharmacology, therapeutic use)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tongue Neoplasms (drug therapy, enzymology, metabolism, pathology)