4.5 Article

Response of intestinal HT-29 cells to the trichothecene mycotoxin deoxynivalenol and its sulfated conjugates

Journal

TOXICOLOGY LETTERS
Volume 295, Issue -, Pages 424-437

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2018.07.007

Keywords

Deoxynivalenol-3-sulfate; Deoxynivalenol-15-sulfate; Cell proliferation; Food contaminant; Mycotoxins; Cytotoxicity

Categories

Funding

  1. Austrian Science Fund (FWF) [SFB F3718, F3702]

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The sulfated forms of the Fusarium toxin deoxynivalenol (DON), deoxynivalenol-3-sulfate (DON-3-Sulf) and deoxynivalenol-15-sulfate (DON-15-Sulf) were recently described, however little is known about their mechanism of action in mammalian cells. DON-3-Sulf and DON-15-Sulf were taken up by HT-29 colon carcinoma cells, although to a lesser extent compared to DON. All three compounds were found to enhance the intracellular ROS level in the dichlorofluorescein assay (>= 1 mu M), even though substantial differences were observed in their cytotoxic potential. In silico modelling highlighted that DON-sulfates do not share the classical mechanism of action of DON, being unable to fit into the ribosomal pocket and trigger the classical ribotoxic stress response. However, DON-3-Sulf and DON-15-Sulf sustained a distinctive proliferative stimulus in HT-29 and activated autophagy. The mechanisms of action of DON-3-Sulf and DON-15-Sulf suggest a potential interplay between the onset of ribosomal inhibition and autophagy activation as an alternative and/or complementary mode of action for DON and its sulfated analogues.

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