Luteolin-7-O-Glucoside Inhibits Oral Cancer Cell Migration and Invasion by Regulating Matrix Metalloproteinase-2 Expression and Extracellular Signal-Regulated Kinase Pathway.

Bharath Kumar Velmurugan,Chia-Chieh Lin,Jen-Tsun Lin,Yi-Ching Chuang,B Mahalakshmi,Mu-Kuan Chen,Yu-Sheng Lo,Ming-Ju Hsieh

doi:10.3390/biom10040502

Abstract

Oral squamous cell carcinoma is the sixth most common type of cancer globally, which is associated with high rates of cancer-related deaths. Metastasis to distant organs is the main reason behind worst prognostic outcome of oral cancer. In the present study, we aimed at evaluating the effects of a natural plant flavonoid, luteolin-7-O-glucoside, on oral cancer cell migration and invasion. The study findings showed that in addition to preventing cell proliferation, luteolin-7-O-glucoside caused a significant reduction in oral cancer cell migration and invasion. Mechanistically, luteolin-7-O-glucoside caused a reduction in cancer metastasis by reducing p38 phosphorylation and downregulating matrix metalloproteinase (MMP)-2 expression. Using a p38 inhibitor, SB203580, we proved that luteolin-7-O-glucoside exerts anti-migratory effects by suppressing p38-mediated increased expression of MMP-2. This is the first study to demonstrate the luteolin-7-O-glucoside inhibits cell migration and invasion by regulating MMP-2 expression and extracellular signal-regulated kinase pathway in human oral cancer cell. The study identifies luteolin-7-O-glucoside as a potential anti-cancer candidate that can be utilized clinically for improving oral cancer prognosis.

Highlights

Oral squamous cell carcinoma that primarily affects the lips, oral cavity, and tongue represents about 90% of all head and neck cancers
To investigate whether luteolin-7-O-glucoside can alter cell proliferation, three oral cancer cell lines, FaDu, HSC-3, and CA9-22, were treated with various concentrations (0, 10, 20, and 40 μM) of luteolin-7-O-glucoside for 24 h, and the cell viability was determined by MTT assay
In addition to cell proliferation, we investigated the effects of luteolin-7-O-glucoside on cell motility

Summary

Introduction

Oral squamous cell carcinoma that primarily affects the lips, oral cavity, and tongue represents about 90% of all head and neck cancers. Despite advancement in diagnostic processes and therapeutic interventions, oral cancer is associated with a high rate of morbidity and mortality [2]. As a result of the initial asymptomatic nature, oral cancer is often diagnosed in the later stage, resulting in distant metastasis and poor prognosis [3,4,5,6]. An overexpression or increased activity of MMPs is associated with higher cancer aggressiveness and poor survival rate [8]. MMPs are a target for developing treatment strategies against cancer. In this context, several studies have shown that selective inhibition of MMP can be associated with better cancer management [9,10,11]

Methods

Results

Discussion

Conclusion