title: Okadaic acid induces apoptosis through the PKR, NF-κB and caspase pathway in human osteoblastic osteosarcoma MG63 cells.
abstract: Okadaic acid (OA) is the major component of diarrheic shellfish poisoning toxins and a potent inhibitor of protein phosphatase 1 and 2A. However, the underlying regulatory mechanisms involved in OA-induced cell death are not well understood. In the present study, we examined the effects of OA on apoptosis of MG63 cells by characterizing apoptotic morphological changes of the cells and DNA fragmentation. The roles of double-stranded RNA-dependent protein kinase (PKR), nuclear factor-κB (NF-κB) and caspase in OA-mediated apoptosis in MG63 cells were also examined. Results showed that OA induced cytotoxicity and apoptosis in MG63 cells at IC50 of 75 nM. A functional PKR pathway is required to induce apoptosis in response to OA treatment. Blockade of NF-κB by ammonium pyrrolidinedithiocarbamate (PDTC) resulted in down-regulation of apoptosis. The caspase-3 and caspase-8 inhibitors blocked apoptosis in MG63 cells. In conclusion, our results imply that OA can induce MG63 cell apoptosis through the PKR, NF-κB and caspase pathway.
authors.affiliation: Department of Histology and Oral Histology, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto, Tokushima 770-8504, Japan. chenling982@163.com
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D006801:Humans; D008387:Marine Toxins / Q000633:toxicity*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019319:Okadaic Acid / Q000633:toxicity*; D009842:Oligopeptides / Q000494:pharmacology; D012516:Osteosarcoma; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D061945:Caspase Inhibitors; D008387:Marine Toxins; D016328:NF-kappa B; D009842:Oligopeptides; D011759:Pyrrolidines; D013859:Thiocarbamates; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C403753:benzyloxycarbonyl-isoleucyl-glutamyl-threonyl-aspartic acid fluoromethyl ketone; D019319:Okadaic Acid; C020972:pyrrolidine dithiocarbamic acid; D019892:eIF-2 Kinase; D053148:Caspase 3; D053181:Caspase 8