Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines

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 PP...

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Main Authors: Miguel del Campo, Héctor Toledo, Néstor Lagos
Format: Article
Language:English
Published: MDPI AG 2013-12-01
Series:Marine Drugs
Subjects:
Online Access:http://www.mdpi.com/1660-3397/11/12/4751
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author Miguel del Campo
Héctor Toledo
Néstor Lagos
author_facet Miguel del Campo
Héctor Toledo
Néstor Lagos
author_sort Miguel del Campo
collection DOAJ
description 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.
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spelling doaj.art-c64230b6526f43a68ae08ad2aaf6d87a2022-12-22T02:21:34ZengMDPI AGMarine Drugs1660-33972013-12-0111124751476010.3390/md11124751md11124751Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell LinesMiguel del Campo0Héctor Toledo1Néstor Lagos2Laboratory of Membrane Biochemistry, Program of Physiology and Biophysics, Faculty of Medicine, University of Chile, Independencia 1027, Correo 7, Santiago 8380000, ChileLaboratory of Molecular Microbiology, Program of Cellular and Molecular Biology, Faculty of Medicine, University of Chile, Independencia 1027, Correo 7, Santiago 8380000, ChileLaboratory of Membrane Biochemistry, Program of Physiology and Biophysics, Faculty of Medicine, University of Chile, Independencia 1027, Correo 7, Santiago 8380000, ChileThe 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.http://www.mdpi.com/1660-3397/11/12/4751okadaic acidgastric cancercolon cancerPP2Aproliferation
spellingShingle Miguel del Campo
Héctor Toledo
Néstor Lagos
Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines
Marine Drugs
okadaic acid
gastric cancer
colon cancer
PP2A
proliferation
title Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines
title_full Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines
title_fullStr Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines
title_full_unstemmed Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines
title_short Okadaic Acid Toxin at Sublethal Dose Produced Cell Proliferation in Gastric and Colon Epithelial Cell Lines
title_sort okadaic acid toxin at sublethal dose produced cell proliferation in gastric and colon epithelial cell lines
topic okadaic acid
gastric cancer
colon cancer
PP2A
proliferation
url http://www.mdpi.com/1660-3397/11/12/4751
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AT hectortoledo okadaicacidtoxinatsublethaldoseproducedcellproliferationingastricandcolonepithelialcelllines
AT nestorlagos okadaicacidtoxinatsublethaldoseproducedcellproliferationingastricandcolonepithelialcelllines