title: Trichlorfon induces apoptosis in SH-SY5Y neuroblastoma cells via the endoplasmic reticulum?
abstract: This study investigated the role of the endoplasmic reticulum pathway in apoptosis induced by trichlorfon in SH-SY5Y human neuroblastoma cells. Flow cytometric analysis demonstrated that trichlorfon and its degradation product dichlorvos-induced apoptosis in a dose-dependent manner and Hoechst 33342 staining experiments revealed trichlorfon/dichlorvos-induced nucleus condensation. Western blot analysis indicated decreased expression of caspase-12 and increased activated caspase-12 in trichlorfon-treated cells compared to a control, suggesting that trichlorfon may induce apoptosis in SH-SY5Y partly via the endoplasmic reticulum. Intracellular Ca(2+) level ([Ca(2+)](i)) in SH-SY5Y cells increased after treatment with trichlorfon but was significantly reduced by pre-treatment with a combination of a calcium channel blocker, an inositol trisphosphate receptor inhibitor, and a ryanodine receptor inhibitor. Percent apoptosis and activated caspase-3 and caspase-12 decreased in pre-treated cells compared to those treated with trichlorfon alone. Trichlorfon-induced apoptosis was also inhibited by the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA). These results suggest that endoplasmic reticulum stress, which is related to calcium, may be involved in the cytotoxicity of trichlorfon.
authors.affiliation: Laboratory of Molecular Toxicology, State Key Laboratory of Integrated Management of Pest Insects and Rodents, Institute of Zoology, Chinese Academy of Sciences, Datunlu Road, Beijing, PR China.
authors.forename: Cheng-Yun
authors.initials: CY
authors.lastname: Liu
authors.forename: Ping-An
authors.initials: PA
authors.lastname: Chang
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008856:Microscopy, Fluorescence; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014236:Trichlorfon / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D014236:Trichlorfon; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium