Anticancer Effect of ERM210 on Liver Cancer Cells Through ROS/Mitochondria-dependent Apoptosis Signaling Pathways

Abstract

Background/Aim: Asian Traditional medicines are renowned for their antitumor properties and are efficacious in the clinical treatment of various cancer types. ERM210 is a Korean traditional medicine comprising nine types of medicinal plants. In the present study, we examined the pro-apoptotic effect and molecular mechanisms of the effects of ERM210 on HepG2 liver cancer cells. Materials and Methods: The cytotoxicity of ERM210 on HepG2 cells was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide and wound-healing assays, and apoptosis and signaling pathways by fluorescence microscopy flow cytometry and western blotting. Results: ERM210 significantly impaired HepG2 cell viability and enhanced mitochondria-dependent cellular apoptosis in a time-and dose-dependent manner by up-regulating the expression of caspases 3, 7 and 9, and of BCL2 apoptosis regulator (BCL2)-associated X, apoptosis regulator (BAX) proteins, whilst down-regulating that of BCL2 protein. Furthermore, ERM210 treatment increased accumulation of cellular and mitochondrial reactive oxygen species (ROS) and significantly inhibited cell migration. Additionally, all these phenomena were reversed by treating with the ROS scavenger N-acetylcysteine. The analysis of signaling proteins revealed that ERM210 significantly up-regulated the phosphorylation of ROS-dependent mitogen-activated protein kinases (p38, extracellular-regulated kinase, and c-Jun Nterminal kinase in HepG2 liver cancer cells. Conclusion: ERM210 exerts anticancer effects in HepG2 liver cancer cells by up-regulating ROS/mitochondria-dependent apoptosis signaling, providing new insight into the possibility of employing this traditional medicine for the clinical treatment of liver cancer.A wide variety of unique traditional herbal medicines abound in Asia. These medicines have numerous advantages over conventional chemotherapy drugs, such as low toxicity, easy absorption, and multi-target action (1, 2). According to the World Health Organization, traditional medicine is "used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness" (3). This underlies the long-established traditional use of herbal-based medicines. It includes herbal medicines and herbal finished products, which contain plants and other combination as active ingredients (4). In recent years, numerous studies have shown that herbal medicine is effective in treating insomnia (3), Alzheimer's disease (5), cardiovascular diseases (6), polycystic ovary syndrome (7), esophageal cancer (8), and other diseases (9, 10). Herbal medicines contain abundant anticancer compounds that directly affect cancer cells and have been utilized as anticancer agents far longer than any of the chemotherapy drugs.Cancer is an intractable human disease. Liver cancer is for the third leading cause of mortality (11). Hepatocellular carcinoma constitutes the primary and most common liver cancer subtype, with contributing risk factors including 2599 This article ...

Peroxiredoxin 5 protects HepG2 cells from ethyl β-carboline-3-carboxylate-induced cell death via ROS-dependent MAPK signalling pathways

“…Redox processes have always existed in cells, and reactive oxygen species (ROS) play vital roles in metabolic processes 8 . ROS act as signalling molecules in biological systems, regulating signalling pathways 9 , maintaining tissue homeostasis 10 , and modulating cell survival and apoptosis 11 . Within the normal physiological concentration range, ROS exert beneficial effects on cell growth and development by minimizing oxidative damage and satisfying energy demands 12 .…”