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

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.

<p>Dual Targeting of Cell Growth and Phagocytosis by Erianin for Human Colorectal Cancer</p>

“…14,15 Interestingly, besides the function on cell growth, apoptosis, and migration, erianin was found to strongly affect the serum levels of cytokines and immune response in liver cancer. 16 More importantly, in addition to the anticancer effects, previous a study also suggested that erianin had no major organ-related toxicities. 12 However, to the best of our knowledge, neither the mechanism nor the effect of erianin on colorectal cancer has been reported.…”

“…8,9 Erianin (2-methoxy-5-[2-(3,4,5-trimethoxyphe-nyl)-ethyl]-phenol; Figure 1A), a natural compound derived from Dendrobium candidum, shows various pharmacological activities and therapeutic potential to inhibit multiple cancers in vivo and in vitro. [10][11][12][13][14][15][16] Li et al demonstrated that erianin inhibited the proliferation of acute promyelocytic leukemia HL-60 cells by regulating the expression of bcl-2 and bax. 10 In addition, erianin caused moderate growth delay in xenografted human hepatoma Bel7402 and melanoma A375.…”

Transferrin-Conjugated Erianin-Loaded Liposomes Suppress the Growth of Liver Cancer by Modulating Oxidative Stress

“…For example, erianin (ERN; 2-methoxy-5-[2- (3,4,5trimethoxyphenyl)-ethyl]-phenol, Figure S1) is isolated from Dendrobium chrysotoxum Lindl, a widely cultivated species of orchid, and has a variety of pharmacological activities, including anti-cancer activities (15,16). We recently confirmed that the anti-liver cancer effects of ERN are attributable to its regulation of oxidative stress-mediated mitochondrial apoptosis and the immune response (17). However, ERN has poor aqueous solubility and can only be solubilized in dimethyl sulfoxide, which limits its use in vivo.…”

<p>Glucometabolic Reprogramming in the Hepatocellular Carcinoma Microenvironment: Cause and Effect</p>

“…26 Oxidative stress can mediate mitochondrial apoptosis and the immune response in liver cancer. 27 Reactive oxygen species (ROS), byproducts of oxygen metabolism, are the main causes of oxidative stress, and their concentration changes play dual functions in the regulation of HCC process. 28,29 Low levels of ROS may induce DNA mutation by oxidative DNA damage, which eventually increases the likelihood of HCC development.…”