Gallic acid inhibits migration and invasion of SCC‑4 human oral cancer cells through actions of NF‑κB, Ras and matrix metalloproteinase-2 and -9

Kuo,Chao-Lin; Lai,Kuang-Chi; Ma,Yi-Shih; Weng,Shu-Wen; Lin,Jing-Pin; Chung,Jing-Gung

doi:10.3892/or.2014.3209

Gallic acid inhibits migration and invasion of SCC‑4 human oral cancer cells through actions of NF‑κB, Ras and matrix metalloproteinase-2 and -9

Authors:
- Chao-Lin Kuo
- Kuang-Chi Lai
- Yi-Shih Ma
- Shu-Wen Weng
- Jing-Pin Lin
- Jing-Gung Chung
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Affiliations: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan, R.O.C., Department of Medicine, China Medical University, Taichung, Taiwan, R.O.C., School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan, R.O.C., Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C., School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C., Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
Published online on: May 23, 2014 https://doi.org/10.3892/or.2014.3209
Pages: 355-361

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Abstract

Oral cancer is one of the major causes of mortality in humans and squamous cell carcinoma is the most common type of oral cancer. Gallic acid (GA) is a natural product that induces cell death through cell cycle arrest and induction of apoptosis. There is no available information on whether GA affects cell migration and invasion of human oral cancer cells. We determined if GA inhibited migration and invasion of SCC-4 (human squamous cell carcinoma) human oral cancer cells. GA significantly inhibited migration and invasion of SCC-4 cells based on results from the wound healing assay and Matrigel Cell Migration Assay and Invasion System. We also showed that GA significantly inhibited matrix metalloproteinase (MMP)-2 and MMP-9 activity. GA reduced protein levels of FAK, MEKK3, p-PERK, p-p38, p-JNK1/2, p-ERK1/2, SOS1, RhoA, Ras, PKC, p-AKT(Thr308), PI3K, NF-κB p65, MMP-2 and MMP-9 in SCC-4 cells. Translocation of NF-κB and RhoA from the cytosol to the nucleus was reduced by GA in SCC-4 cells. In summary, GA inhibits migration and invasion of SCC-4 cells by inhibiting NF-κB expression causing suppression of MMP-2 and MMP-9 activity. GA may have potential as a therapeutic agent for the treatment of oral cancer.

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