Total Flavonoids from Radix Glycyrrhiza Exert Anti-Inflammatory and Antitumorigenic Effects by Inactivating iNOS Signaling Pathways.

Yi-Xin Jiang,Dan-Dan Zhang,Yi-Feng Pan,Ka Bian,Xi-Min Wu,Yue Yang,Yang-Yi Dai

doi:10.1155/2018/6714282

Abstract

Inducible nitric oxide synthase (iNOS) plays an important role in inflammation, which has also been considered as a major driver of breast cancer disease progression. Radix Glycyrrhiza (RG) has been broadly used for its anti-inflammatory and antitumorigenic effects. However, the mechanisms of regulation of iNOS in inflammation and cancer have not been fully explored. Total flavonoids isolated from RG (TFRG) exhibited anti-inflammatory activity through the regulation of ERK/NF-κB/miR-155 signaling and suppression of iNOS expression in LPS/IFN-γ stimulated RAW264.7 macrophages without cytotoxicity. TFRG also markedly reduced tumor mass of breast cancer cell MDA-MB-231 xenografts with suppression of iNOS expression, formation of 3-nitrotyrosine (3-NT), and inactivation of protumorigenic JAK2/STAT3 signaling pathway. These results suggested that TFRG limited the development of breast cancer and inflammation due to its property of iNOS inhibition.

Highlights

The linkage between chronic inflammation and tumor development has been studied for decades [1, 2]
Inducible nitric oxide synthase, one of three enzyme isoforms of nitric oxide synthase (NOS), is the key enzyme expressed under inflammatory conditions and capable of producing high levels of nitric oxide (NO), which impact the redox state of cells and induce oxidation of proteins, lipids, and DNA
We report that total flavonoids isolated from Radix Glycyrrhiza (RG) (TFRG) exhibited anti-inflammatory activity through the regulation of ERK/Nuclear factor-kappa B ERK (NF-κB)/miR-155 signaling and suppression of Inducible nitric oxide synthase (iNOS) expression

Summary

Introduction

The linkage between chronic inflammation and tumor development has been studied for decades [1, 2]. In estrogen receptor- (ER-) negative breast cancer patients, the iNOS expression is positively correlated with tumor-node metastasis (TNM), a marker clinically used to predict patient survival [6]. Several iNOS inhibitors have demonstrated efficacy in reduction of metastases and inhibition of cancer stem cell renewal in triple-negative breast cancer [8]. We hypothesize that plant extracts with anti-inflammatory capability targeting iNOS and oxidative/nitrosative stress are useful chemopreventive agents against breast cancer growth and/or metastasis. We report that total flavonoids isolated from RG (TFRG) exhibited anti-inflammatory activity through the regulation of ERK/NF-κB/miR-155 signaling and suppression of iNOS expression. TFRG markedly reduced tumor mass of MDA-MB-231 xenografts with inhibition of iNOS and formation of nitrotyrosine by JAK2/STAT3 signaling pathway

Materials and Methods

Results

Findings

Discussion