title: Okadaic acid toxin at sublethal dose produced cell proliferation in gastric and colon epithelial cell lines.
abstract: The aim of this study was to analyze the effect of Okadaic Acid (OA) on the proliferation of gastric and colon epithelial cells, the main target tissues of the toxin. We hypothesized that OA, at sublethal doses, activates multiple signaling pathways, such as Erk and Akt, through the inhibition of PP2A. To demonstrate this, we carried out curves of doses and time response against OA in AGS, MKN-45 and Caco 2 cell lines, and found an increase in the cell proliferation at sublethal doses, at 24 h or 48 h exposure. Indeed, cells can withstand high concentrations of the toxin at 4 h exposure, the time chosen considering the maximum time before total gastric emptying. We have proved that this increased proliferation is due to an overexpression of Cyclin B, a cyclin that promotes the passage from G2 to mitosis. In addition, we have demonstrated that OA induces activation of Akt and Erk in the three cells lines, showing that OA can activate pathways involved in oncogenesis. In conclusion, this study contributes to the knowledge about the possible effects of chronic OA consumption.
authors: Laboratory of Membrane Biochemistry, Program of Physiology and Biophysics, Faculty of Medicine, University of Chile, Independencia 1027, Correo 7, Santiago 8380000, Chile. nlagos@med.uchile.cl.
authors: Miguel
authors: M
authors: del Campo
authors: Héctor
authors: H
authors: Toledo
authors: Néstor
authors: N
authors: Lagos
mesh_terms: D018938:Caco-2 Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019319:Okadaic Acid / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013270:Stomach / Q000187:drug effects*
chemical_list: D019926:Cyclin B; D019319:Okadaic Acid; D051057:Proto-Oncogene Proteins c-akt