PMID- 28816938 OWN - NLM STAT- MEDLINE DCOM- 20170905 LR - 20221222 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 96 IP - 33 DP - 2017 Aug TI - Advanced glycation end products promote ChREBP expression and cell proliferation in liver cancer cells by increasing reactive oxygen species. PG - e7456 LID - 10.1097/MD.0000000000007456 [doi] LID - e7456 AB - 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. FAU - Chen, Hanbei AU - Chen H AD - Department of Endocrinology, Xinhua Hospital Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian Department of Gastroenterology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Li, Yakui AU - Li Y FAU - Zhu, Yemin AU - Zhu Y FAU - Wu, Lifang AU - Wu L FAU - Meng, Jian AU - Meng J FAU - Lin, Ning AU - Lin N FAU - Yang, Dianqiang AU - Yang D FAU - Li, Minle AU - Li M FAU - Ding, WenJin AU - Ding W FAU - Tong, Xuemei AU - Tong X FAU - Su, Qing AU - Su Q LA - eng PT - Journal Article PT - Observational Study PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors) RN - 0 (Glycation End Products, Advanced) RN - 0 (MLXIPL protein, human) RN - 0 (RNA, Messenger) RN - 0 (Reactive Oxygen Species) RN - 0 (Transcription Factors) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM EIN - Medicine (Baltimore). 2017 Dec;96(50):e9318. PMID: 29390398 MH - Acetylcysteine/pharmacology MH - Apoptosis MH - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*biosynthesis MH - Carcinoma, Hepatocellular/*metabolism MH - Cell Proliferation MH - Cell Survival MH - Glycation End Products, Advanced/*pharmacokinetics MH - Humans MH - Liver Neoplasms/*metabolism MH - RNA, Messenger/biosynthesis MH - Reactive Oxygen Species/*metabolism MH - Real-Time Polymerase Chain Reaction MH - Transcription Factors/metabolism MH - Tumor Cells, Cultured PMC - PMC5571675 COIS- The authors have no conflicts of interest to disclose. EDAT- 2017/08/18 06:00 MHDA- 2017/09/07 06:00 PMCR- 2017/08/18 CRDT- 2017/08/18 06:00 PHST- 2017/08/18 06:00 [entrez] PHST- 2017/08/18 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/08/18 00:00 [pmc-release] AID - 00005792-201708180-00005 [pii] AID - MD-D-16-04689 [pii] AID - 10.1097/MD.0000000000007456 [doi] PST - ppublish SO - Medicine (Baltimore). 2017 Aug;96(33):e7456. doi: 10.1097/MD.0000000000007456.