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

Journal of Oral Pathology and Medicine - Tập 44 Số 9 - Trang 699-706 - 2015
Feng‐Yan Lin1,2, Yi‐Hsien Hsieh3, Shun‐Fa Yang4,2, Chang‐Tai Chen5,6, Chih‐Hsin Tang7,8, Ming‐Yung Chou9,6, Yi‐Ting Chuang2, Chiao‐Wen Lin9,5, Mu‐Kuan Chen10,2
1Department of Emergency Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
2Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
3Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
4Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
5Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan
6School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
7Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan
8Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
9Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
10Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

Tóm tắt

BackgroundNaturally 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.MethodsCell 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.ResultsWe 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.ConclusionIn 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.

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