title: FV-429 Induced Apoptosis Through ROS-Mediated ERK2 Nuclear Translocation and p53 Activation in Gastric Cancer Cells.
abstract: Following our previous finding which revealed that FV-429 induces apoptosis in human hepatocellular carcinoma HepG2 cells, in this study, we found that FV-429 could also induce apoptosis in human gastric cancer cells. Firstly, FV-429 inhibited the viability of BGC-823 and MGC-803 cells with IC50 values in the range of 38.10 ± 6.28 and 31.53 ± 6.84 µM for 24 h treatment by MTT-assay. Secondly, FV-429 induced apoptosis in BGC-823 and MGC-803 cells through the mitochondrial-mediated pathway, showing an increase in Bax/Bcl-2 ratios, and caspase-9 activation, without change in caspase-8. Further research revealed that the mitogen-activated protein kinases, including c-Jun N-terminal kinase, extracellular regulated kinase, and p38 mitogen-activated protein kinase, could be activated by FV-429-induced high level ROS. Moreover, FV-429 also promoted the ERK2 nuclear translocation, resulting in the co-translocation of p53 to the nucleus and increased transcription of p53-regulated proapoptotic genes. FV-429 significantly inhibited the nude mice xenograft tumors growth of BGC-823 or MGC-803 cells in vivo.
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
authors: Yuxin
authors: Y
authors: Zhou
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
authors: Libin
authors: L
authors: Wei
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
authors: Haiwei
authors: H
authors: Zhang
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
authors: Qinsheng
authors: Q
authors: Dai
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
authors: Zhiyu
authors: Z
authors: Li
authors: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, P.R. China.
authors: Boyang
authors: B
authors: Yu
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
authors: Qinglong
authors: Q
authors: Guo
authors: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, JiangSu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, P.R. China.
authors: Na
authors: N
authors: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C569690:FV-429 compound; D005419:Flavonoids; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1
keywords: EXTRACELLULAR REGULATED KINASE; NUCLEAR TRANSLOCATION; REACTIVE OXYGEN SPECIES; p53