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

Jong-Hwei S Pang,Sheng-Teng Huang,Hsiao-Ting Wu,Jia-Hau Yen

doi:10.3390/ijms18071354

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.

Highlights

Gallic acid is a trihydroxybenzoic acid commonly present in many natural herbal plants and in some prescribed Chinese medicines as an active component [1,2,3,4]
To test the hypothesis that matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinases (TIMPs)-1were both regulated by gallic acid and contributed to the inhibited matrix invasion of NPC-BM1 cells, we examined the mRNA and protein expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in NPC-BM1 cells after gallic acid treatment for 24 h by RT/real-time PCR and western blot, respectively
We investigated the effect of gallic acid, a major active component of Phyllanthus urinaria, on the matrix invasion of NPC-BM1 cells and related molecular mechanism

Summary

Introduction

Gallic acid is a trihydroxybenzoic acid commonly present in many natural herbal plants and in some prescribed Chinese medicines as an active component [1,2,3,4]. This compound has several important pharmacological properties including anti-inflammatory, anti-tumor, anti-mutagenic, anti-allergic, antiulcer, antioxidant, and antiviral activities [5,6]. Ellagic acid has been demonstrated in our published studies to contribute to the anti-angiogenic effect of P. urinaria by reducing MMP-2 secretion and inhibiting MMP-2 activity [3,4]

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Conclusion