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


CONCLUSIONS
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.
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Feng-Yan
FY
Lin
Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Yi-Hsien
YH
Hsieh
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
Shun-Fa
SF
Yang
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.
Chang-Tai
CT
Chen
Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.|Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
Chih-Hsin
CH
Tang
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
Ming-Yung
MY
Chou
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Yi-Ting
YT
Chuang
Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan.|Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
Chiao-Wen
CW
Lin
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan.
Mu-Kuan
MK
Chen
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D013267:Stilbenes / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate; D000077185:Resveratrol
MMP-9; invasion; oral cancer; resveratrol