title: The synthesized novel fluorinated compound (LJJ-10) induces death receptor- and mitochondria-dependent apoptotic cell death in the human osteogenic sarcoma U-2 OS cells.
abstract: We designed the 6-fluoro-2-(3-fluorophenyl)-4-substituted anilinoquinazoline derivatives as less toxic anti-cancer candidates. Our result demonstrated that LJJ-10 has greater cytotoxicity than that of the other compounds in human osteogenic sarcoma U-2 OS cells. LJJ-10-induced apoptosis was associated with enhancing ROS generation, DNA damage, and an increase of the protein levels of Fas, FasL, FADD, caspase-8, cytochrome c, Apaf-1, AIF, Endo G, caspase-9 and caspase-3 in U-2 OS cells. LJJ-10-triggered growth inhibition was significantly attenuated by N-acetylcysteine, cyclosporine A, anti-FasL monoclonal antibody, and caspase-8, -9 and -3 specific inhibitors in U-2 OS cells. We suggest that LJJ-10-induced apoptotic cell death in U-2 OS cells through death receptor- and mitochondria-dependent apoptotic signaling pathways.
authors.affiliation: School of Pharmacy, China Medical University, Taichung 404, Taiwan. mjhour7730@gmail.com
authors.forename: Mann-Jen
authors.initials: MJ
authors.lastname: Hour
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Tai-Lin
authors.initials: TL
authors.lastname: Chen
authors.forename: Kuan-Tin
authors.initials: KT
authors.lastname: Chen
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Jing-Gung
authors.initials: JG
authors.lastname: Chung
authors.forename: Chi-Cheng
authors.initials: CC
authors.lastname: Lu
authors.forename: Chia-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Chuang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C569175:6-fluoro-(3-fluorophenyl)-4-(3-methoxyanilino)quinazoline; C494829:AIFM1 protein, human; C506592:APAF1 protein, human; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; D053477:Apoptotic Protease-Activating Factor 1; C505533:FADD protein, human; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D016166:Free Radical Scavengers; D011799:Quinazolines; D017382:Reactive Oxygen Species; D019014:fas Receptor; D016572:Cyclosporine; D045304:Cytochromes c; D020169:Caspases; D000111:Acetylcysteine