Comparative Analysis of the Cytotoxic Effects of Okadaic Acid-Group Toxins on Human Intestinal Cell Lines

Marine Drugs

Pierre-Jean Ferron¹  Kevin Hogeveen¹  Valérie Fessard¹ 

[1] ANSES, Fougères Laboratory, Toxicology of Contaminants Unit, French Agency for Food, Environmental and Occupational Health & Safety, Fougères 35302, France;

关键词: high content analysis;    okadaic acid;    dinophysistoxins;    apoptosis;    γ-H2AX;    inflammation;    proliferation;   

DOI  :  10.3390/md12084616

来源: mdpi

【 摘 要 】

The phycotoxin, okadaic acid (OA) and dinophysistoxin 1 and 2 (DTX-1 and -2) are protein phosphatase PP2A and PP1 inhibitors involved in diarrhetic shellfish poisoning (DSP). Data on the toxicity of the OA-group toxins show some differences with respect to the in vivo acute toxicity between the toxin members. In order to investigate whether OA and congeners DTX-1 and -2 may induce different mechanisms of action during acute toxicity on the human intestine, we compared their toxicological effects in two in vitro intestinal cell models: the colorectal adenocarcinoma cell line, Caco-2, and the intestinal muco-secreting cell line, HT29-MTX. Using a high content analysis approach, we evaluated various cytotoxicity parameters, including apoptosis (caspase-3 activation), DNA damage (phosphorylation of histone H2AX), inflammation (translocation of NF-κB) and cell proliferation (Ki-67 production). Investigation of the kinetics of the cellular responses demonstrated that the three toxins induced a pro-inflammatory response followed by cell cycle disruption in both cell lines, leading to apoptosis. Our results demonstrate that the three toxins induce similar effects, as no major differences in the cytotoxic responses could be detected. However DTX-1 induced cytotoxic effects at five-fold lower concentrations than for OA and DTX-2.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.