Research Paper Volume 11, Issue 22 pp 10284—10300

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

Xinrui Zhang 1, , Yingwu Wang 1, , Xin Li 2, , Anhui Yang 1, , Zhiwen Li 3, , Di Wang 1, 2, ,

  • 1 School of Life Sciences, Jilin University, Changchun 130012, China
  • 2 Zhuhai College of Jilin University, Jilin University, Zhuhai 519041, China
  • 3 Department of Anesthesiology, The First Hospital of Jilin University, Changchun 130021, China

received: May 30, 2019 ; accepted: November 7, 2019 ; published: November 20, 2019 ;

https://doi.org/10.18632/aging.102456
How to Cite

Copyright © 2019 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.

Abbreviations

Bcl-2: B-cell lymphoma 2; ELISA: enzyme-linked immunosorbent assay; Erk: extracellular regulated protein kinases; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GM-CSF: granulocyte-macrophage colony stimulating factor; HO: heme oxygenase; IKB-α: NF-kappa-B inhibitor alpha; IKK: IKB kinase; IL-6: interleukin-6; IL-10: interleukin-10; MMP: mitochondrial membrane potential; MMPs: matrix metalloproteinases; MMP-2: matrix metalloproteinase 2; MMP-9: matrix metalloproteinase 9; PUMA: p53 upregulated modulator of apoptosis; NF-κB: nuclear factor-kappa B; Nrf2: nuclear factor erythroid 2-related factor 2; PARP: poly ADP-ribose polymerase; PMSF: phenylmethanesulfonyl fluoride; RIPA: radioimmunoprecipitation assay; ROS: reactive oxygen species; SOD-1: Superoxide Dismutase-1; SOD-2: Superoxide Dismutase-2; TNF-α: tumor necrosis factor-α.