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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 |
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| Authors: | Hour Mann-Jen Yang Jai-Sing Chen Tai-Lin Chen Kuan-Tin Kuo Sheng-Chu Chung Jing-Gung Lu Chi-Cheng Chen Chia-Yi Chuang Yi-Hsuan |
| Institution: | a School of Pharmacy, China Medical University, Taichung 404, Taiwan b Department of Pharmacology, China Medical University, Taichung 404, Taiwan c Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 404, Taiwan d Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan e Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan |
| 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. |
| Keywords: | 6-Fluoro-2-(3-fluorophenyl)-4-substituted anilinoquinazoline derivatives LJJ-10 U-2 OS cells Death receptor Mitochondrial apoptotic signaling |
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