title: 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.
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.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Chao-Lin
authors.initials: CL
authors.lastname: Kuo
authors.affiliation: Department of Medicine, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Kuang-Chi
authors.initials: KC
authors.lastname: Lai
authors.affiliation: School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, Taiwan, R.O.C.
authors.forename: Yi-Shih
authors.initials: YS
authors.lastname: Ma
authors.affiliation: Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Weng
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Jing-Pin
authors.initials: JP
authors.lastname: Lin
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005707:Gallic Acid / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009062:Mouth Neoplasms / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D005707:Gallic Acid; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D018631:ras Proteins