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

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-kappaB p65, MMP-2 and MMP-9 in SCC-4 cells. Translocation of NF-kappaB 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-kappaB expression causing suppression of MMP-2 and MMP-9 activity. GA may have potential as a therapeutic agent for the treatment of oral cancer.