Gallic Acid Inhibited Matrix Invasion and AP-1/ETS-1-Mediated MMP-1 Transcription in Human Nasopharyngeal Carcinoma Cells

Abstract

Gallic acid is a trihydroxybenzoic acid found in natural herbal plants. Gallic acid has been reported to inhibit the migration and invasive capability of various cancers. Little is known about the underlying mechanisms of invasion responsible for cancer metastasis via gallic acid. The present study was intended to investigate the anti-invasive effect of gallic acid on human nasopharyngeal carcinoma cells (NPC-BM1) and its related mechanism. Gallic acid inhibited the invasion of NPC-BM1 cells dose- and time-dependently without significant cytotoxic effect. Affymetrix oligonucleotide microarray analysis revealed matrix metalloproteinase-1 (MMP-1) as the most down-regulated gene in NPC-BM1 cells by gallic acid. The cytosolic and secreted MMP-1 levels were both found to be inhibited by gallic acid as demonstrated by western blot analysis and ELISA respectively. The mRNA expression and transcription of MMP-1 gene was also down-regulated as determined by RT/real-time PCR and promoter activity assay. The expression of two major transcription binding factors in the MMP-1 promoter, AP-1 and ETS-1, were demonstrated to be reduced by gallic acid in NPC-BM1 cells. The effect of gallic acid was associated with the inhibition of p38 MAPK signaling pathway. In addition, gallic acid enhanced the gene expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) which further suppressed the MMP-1 activity. These findings may be useful to develop a novel chemotherapeutic agent to inhibit the metastasis of nasopharyngeal cancer.

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

“…GA reduced nuclear and cytoplasmatic DNA methyltransferases in H1299 cells [37]. GA was also found to be a potent inhibitor of HDAC8 and class IIa/b HDAC activity [38].In addition, GA demonstrated anti-invasive effects in human nasopharyngeal carcinoma cells NPC-BM1 through the inhibition of p38 MAPK signaling pathway, this was due to suppressed transcription of MMP-1 by down-regulation of Ets1 and c-Jun, c-fos of the AP-1 [39]. In case of AGS cells, GA up-regulated of RhoB and the down-regulated Akt/small GTPase signals and NF-κB activity inhibited cell migration [40].…”

Soya-cerebroside reduces IL-1β-induced MMP-1 production in chondrocytes and inhibits cartilage degradation: implications for the treatment of osteoarthritis

“…AP-1 is a critical transcription factor that controls MMP-1 production (Pang, Yen, Wu, & Huang, 2017;Wu, Lin, Tsai, Huang, & Tang, 2018). We examined whether AP-1 controls IL-1β-induced MMP-1 production.…”

Glucose suppresses IL‐1β‐induced MMP‐1 expression through the FAK, MEK, ERK, and AP‐1 signaling pathways

“…Transcription factor AP-1 is known to regulate MMP-1 expression. 29 We hypothesized that AP-1 may regulate IL-1β-induced MMP-1 expression. Incubation of cells with AP-1 inhibitors (curcumin and tanshinone) blocked IL-1β-induced MMP-1 expression ( Figure 5A).…”