Liquiritin inhibits proliferation and induces apoptosis in HepG2 hepatocellular carcinoma cells via the ROS-mediated MAPK/AKT/NF-κB signaling pathway

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2020-10, Vol.393 (10), p.1987-1999
• Main Authors: Wang, Jia-Ru, Li, Tian-Zhu, Wang, Cheng, Li, Shu-Mei, Luo, Ying-Hua, Piao, Xian-Ji, Feng, Yu-Chao, Zhang, Yi, Xu, Wan-Ting, Zhang, Yu, Zhang, Tong, Wang, Shi-Nong, Xue, Hui, Wang, Hong-Xing, Cao, Long-Kui, Jin, Cheng-Hao
• Format: Article
• Language: English
• Subjects: Acetylcysteine; AKT protein; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Bcl-2 protein; Biomedical and Life Sciences; Biomedicine; c-Jun protein; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - metabolism; Caspase-3; Cell cycle; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - physiology; Cell Survival - drug effects; Cell Survival - physiology; Cyclin B; Cytochrome c; Dose-Response Relationship, Drug; Enzyme inhibitors; Extracellular signal-regulated kinase; Flavanones - pharmacology; Flavanones - therapeutic use; Flow cytometry; Glucosides - pharmacology; Glucosides - therapeutic use; Glycyrrhiza; Hep G2 Cells; Hepatocellular carcinoma; Humans; JNK protein; Kinases; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; MAP kinase; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Membrane potential; Mitochondria; Molecular modelling; Neurosciences; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB protein; Original Article; Pharmacology/Toxicology; Phosphorylation; Poly(ADP-ribose) polymerase; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Signal transduction; Transcription factors
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-019-01763-7

Liquiritin (LIQ), a major constituent of Glycyrrhiza Radix, exhibits various pharmacological activities. In this study, to explore the potential anti-cancer effects and its underlying molecular mechanisms of LIQ in hepatocellular carcinoma (HCC) cells. LIQ significantly decreased viability and induced apoptosis in HepG2 cells by decreasing mitochondrial membrane potential and regulating Bcl-2 family proteins, cytochrome c, cle-caspase-3, and cle-PARP. The cell cycle analysis and western blot analysis revealed that LIQ induced G2/M phase arrest through increased expression of p21 and decreased levels of p27, cyclin B, and CDK1/2. The flow cytometry and western blot analysis also suggested that LIQ promoted the accumulation of ROS in HepG2 cells and up-regulated the phosphorylation expression levels of p38 kinase, c-Jun N-terminal kinase (JNK), and inhibitor of NF-κB (IκB-α); the phosphorylation levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), signal transducer activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) were down-regulated. However, these effects were reversed by N-acetyl- l -cysteine (NAC), MAPK, and AKT inhibitors. The findings demonstrated that LIQ induced cell cycle arrest and apoptosis via the ROS-mediated MAPK/AKT/NF-κB signaling pathway in HepG2 cells, and the LIQ may serve as a potential therapeutic agent for the treatment of human HCC.