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 (≥ 1μM), 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.

Response of intestinal HT-29 cells to the trichothecene mycotoxin deoxynivalenol and its sulfated conjugates / Del Favero, Giorgia; Woelflingseder, Lydia; Braun, Dominik; Puntscher, Hannes; Kütt, Mary-Liis; Dellafiora, Luca; Warth, Benedikt; Pahlke, Gudrun; Dall'Asta, Chiara; Adam, Gerhard; Marko, DORIS HANNELORE. - In: TOXICOLOGY LETTERS. - ISSN 0378-4274. - 295:(2018), pp. 424-437. [10.1016/j.toxlet.2018.07.007]

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

Dellafiora, Luca;Dall'Asta, Chiara;MARKO, DORIS HANNELORE
2018-01-01

Abstract

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 (≥ 1μM), 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.
2018
Response of intestinal HT-29 cells to the trichothecene mycotoxin deoxynivalenol and its sulfated conjugates / Del Favero, Giorgia; Woelflingseder, Lydia; Braun, Dominik; Puntscher, Hannes; Kütt, Mary-Liis; Dellafiora, Luca; Warth, Benedikt; Pahlke, Gudrun; Dall'Asta, Chiara; Adam, Gerhard; Marko, DORIS HANNELORE. - In: TOXICOLOGY LETTERS. - ISSN 0378-4274. - 295:(2018), pp. 424-437. [10.1016/j.toxlet.2018.07.007]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2849143
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