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ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells

Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic c...

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Autores principales: Celesia, Adriana, Morana, Ornella, Fiore, Tiziana, Pellerito, Claudia, D’Anneo, Antonella, Lauricella, Marianna, Carlisi, Daniela, De Blasio, Anna, Calvaruso, Giuseppe, Giuliano, Michela, Emanuele, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663760/
https://www.ncbi.nlm.nih.gov/pubmed/33143349
http://dx.doi.org/10.3390/ijms21218135
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author Celesia, Adriana
Morana, Ornella
Fiore, Tiziana
Pellerito, Claudia
D’Anneo, Antonella
Lauricella, Marianna
Carlisi, Daniela
De Blasio, Anna
Calvaruso, Giuseppe
Giuliano, Michela
Emanuele, Sonia
author_facet Celesia, Adriana
Morana, Ornella
Fiore, Tiziana
Pellerito, Claudia
D’Anneo, Antonella
Lauricella, Marianna
Carlisi, Daniela
De Blasio, Anna
Calvaruso, Giuseppe
Giuliano, Michela
Emanuele, Sonia
author_sort Celesia, Adriana
collection PubMed
description Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silencing by RNA interference markedly increased the anti-tumor efficacy of the compound. Moreover, as a consequence of ROS production, TBT-F increased the levels of glucose regulated protein 78 (Grp78) and C/EBP homologous protein (CHOP), two ER stress markers. Interestingly, Grp78 silencing produced significant decreasing effects on the levels of the autophagic proteins p62 and LC3-II, while only p62 decreased in CHOP-silenced cells. Taken together, these results indicate that ROS-dependent ER stress and autophagy play a major role in the TBT-F action mechanism in colon cancer cells and open a new perspective to consider the compound as a potential candidate for colon cancer treatment.
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spelling pubmed-76637602020-11-14 ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells Celesia, Adriana Morana, Ornella Fiore, Tiziana Pellerito, Claudia D’Anneo, Antonella Lauricella, Marianna Carlisi, Daniela De Blasio, Anna Calvaruso, Giuseppe Giuliano, Michela Emanuele, Sonia Int J Mol Sci Article Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silencing by RNA interference markedly increased the anti-tumor efficacy of the compound. Moreover, as a consequence of ROS production, TBT-F increased the levels of glucose regulated protein 78 (Grp78) and C/EBP homologous protein (CHOP), two ER stress markers. Interestingly, Grp78 silencing produced significant decreasing effects on the levels of the autophagic proteins p62 and LC3-II, while only p62 decreased in CHOP-silenced cells. Taken together, these results indicate that ROS-dependent ER stress and autophagy play a major role in the TBT-F action mechanism in colon cancer cells and open a new perspective to consider the compound as a potential candidate for colon cancer treatment. MDPI 2020-10-30 /pmc/articles/PMC7663760/ /pubmed/33143349 http://dx.doi.org/10.3390/ijms21218135 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Celesia, Adriana
Morana, Ornella
Fiore, Tiziana
Pellerito, Claudia
D’Anneo, Antonella
Lauricella, Marianna
Carlisi, Daniela
De Blasio, Anna
Calvaruso, Giuseppe
Giuliano, Michela
Emanuele, Sonia
ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
title ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
title_full ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
title_fullStr ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
title_full_unstemmed ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
title_short ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
title_sort ros-dependent er stress and autophagy mediate the anti-tumor effects of tributyltin (iv) ferulate in colon cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663760/
https://www.ncbi.nlm.nih.gov/pubmed/33143349
http://dx.doi.org/10.3390/ijms21218135
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