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

Abstract

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.

• Authors: Jia-Ru Wang, Tian-Zhu Li, Cheng Wang, Shu-Mei Li, Ying-Hua Luo, Xian-Ji Piao, Yu-Chao Feng, Yi Zhang, Wan-Ting Xu, Yu Zhang, Tong Zhang, Shi-Nong Wang, Hui Xue, Hong-Xing Wang, Long-Kui Cao, Cheng-Hao Jin
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 393 Issue 10 Pg. 1987-1999 (10 2020) ISSN: 1432-1912 [Electronic] Germany
• PMID: 31956937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Flavanones
• Glucosides
• NF-kappa B
• Reactive Oxygen Species
• Proto-Oncogene Proteins c-akt
• liquiritin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Apoptosis (drug effects, physiology)
• Carcinoma, Hepatocellular (drug therapy, metabolism)
• Cell Proliferation (drug effects, physiology)
• Cell Survival (drug effects, physiology)
• Dose-Response Relationship, Drug
• Flavanones (pharmacology, therapeutic use)
• Glucosides (pharmacology, therapeutic use)
• Glycyrrhiza
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, metabolism)
• MAP Kinase Signaling System (drug effects, physiology)
• NF-kappa B (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)