Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species.

Abstract

The aim of the study was to elucidate the mechanism by which advanced glycation end products (AGEs) promote cell proliferation in liver cancer cells.We treated liver cancer HepG2 cells with 200 mg/L AGEs or bovine serum albumin (BSA) and assayed for cell viability, cell cycle, and apoptosis. We performed real-time PCR and Western blot analysis for RNA and protein levels of carbohydrate responsive element-binding protein (ChREBP) in AGEs- or BSA-treated HepG2 cells. We analyzed the level of reactive oxygen species (ROS) in HepG2 cells treated with AGEs or BSA.We found that increased S-phase cell percentage and decreased apoptosis contributed to AGEs-induced liver cancer cell proliferation. Real-time PCR and Western blot analysis showed that AGEs stimulated RNA and protein levels of ChREBP, a transcription factor promoting glycolysis and maintaining cell proliferation in liver cancer cells. Intriguingly, the level of ROS was higher in AGEs-treated liver cancer cells. Treating liver cancer cells with antioxidant N-acetyl cystein (NAC) partly blocked AGEs-induced ChREBP expression and cell proliferation.Our results suggest that the AGEs-ROS-ChREBP pathway plays a critical role in promoting ChREBP expression and liver cancer cell proliferation.

• Authors: Hanbei Chen, Yakui Li, Yemin Zhu, Lifang Wu, Jian Meng, Ning Lin, Dianqiang Yang, Minle Li, WenJin Ding, Xuemei Tong, Qing Su
• Journal: Medicine (Medicine (Baltimore)) Vol. 96 Issue 33 Pg. e7456 (Aug 2017) ISSN: 1536-5964 [Electronic] United States
• PMID: 28816938 (Publication Type: Journal Article, Observational Study)

Chemical References

• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
• Glycation End Products, Advanced
• MLXIPL protein, human
• RNA, Messenger
• Reactive Oxygen Species
• Transcription Factors
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Apoptosis
• Basic Helix-Loop-Helix Leucine Zipper Transcription Factors (biosynthesis)
• Carcinoma, Hepatocellular (metabolism)
• Cell Proliferation
• Cell Survival
• Glycation End Products, Advanced (pharmacokinetics)
• Humans
• Liver Neoplasms (metabolism)
• RNA, Messenger (biosynthesis)
• Reactive Oxygen Species (metabolism)
• Real-Time Polymerase Chain Reaction
• Transcription Factors (metabolism)
• Tumor Cells, Cultured