The anti-carcinogenesis properties of erianin in the modulation of oxidative stress-mediated apoptosis and immune response in liver cancer.

Xinrui Zhang,Di Wang,Xin Li,Anhui Yang,Yingwu Wang,Zhiwen Li

doi:10.18632/aging.102456

Abstract

In this study, erianin was found to reduce the viability of cancer cells, inhibit their proliferation and migration, induce G2/M phase arrest, enhance cancer cell apoptosis, promote an increase in levels of intracellular reactive oxygen species and a decrease in mitochondrial membrane potential, and regulate the expression levels of anti- and pro-apoptosis-related proteins in HepG2 and SMMC-7721 cells. Erianin inhibited tumor growth in HepG2- and SMMC-7721-xenograft tumor nude mouse models, reduced the expression levels of anti-apoptosis proteins and enhanced the expression levels of pro-apoptosis proteins in tumor tissues. Erianin inhibited tumor growth in immunosuppressed BALB/c mice bearing heterotopic tumors. Among 111 types of cytokines detected in proteome profiling of tumor tissues, erianin substantially influenced levels of 38 types of cytokines in HepG2-xenografted tumors and of 15 types of cytokines in SMMC-7721-xenografted tumors, most of which are related to immune functions. Erianin strongly affected the serum levels of cytokines, and regulated the activation of nuclear factor-kappa B (NF-κB), and the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream proteins in spleen. The anti-liver cancer properties of erianin were found to be related mostly to its modulation of oxidative stress-mediated mitochondrial apoptosis and immune response.

Highlights

Liver cancer is a common malignant tumor, ranking third as the cause of cancer-related deaths worldwide [1]
This study investigated the anti–liver cancer properties of erianin in HepG2 and SMMC-7721 cells and in xenografted tumor nude mice and BALB/c mice models
In the cell scratch test, the migration ability of liver cancer cells was significantly inhibited after 24 h of co-culture with erianin (P < 0.05, Figure 1C and Supplementary Figure 1B)

Summary

Introduction

Liver cancer is a common malignant tumor, ranking third as the cause of cancer-related deaths worldwide [1]. As the body’s chief detoxification organ, the liver is sensitive to oxidative stress, which is responsible for cell apoptosis, a prominent feature of liver disease [4]. Oxidative stress leads to the over-accumulation of intracellular reactive oxygen species (ROS) and/or dysfunction of mitochondrial metabolism, leading to mitochondrial apoptosis [5]. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important factor controlling oxidative stress and can regulate the expressions of antioxidant enzymes such as heme oxygenase-1 (HO-1) [6]. The HO-system is considered to be central to the stress response [7] and to protect the mitochondrial membrane potential via the inhibition of oxidative damage [8]

Methods

Results

Conclusion