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Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells

The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only...

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Autores principales: Isono, Makoto, Sato, Akinori, Okubo, Kazuki, Asano, Takako, Asano, Tomohiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838685/
https://www.ncbi.nlm.nih.gov/pubmed/27712589
http://dx.doi.org/10.3727/096504016X14666990347635
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author Isono, Makoto
Sato, Akinori
Okubo, Kazuki
Asano, Takako
Asano, Tomohiko
author_facet Isono, Makoto
Sato, Akinori
Okubo, Kazuki
Asano, Takako
Asano, Tomohiko
author_sort Isono, Makoto
collection PubMed
description The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only increases unfolded proteins by suppressing HSP90 but also acts as a proteasome inhibitor. We thought that belinostat and ritonavir together would induce endoplasmic reticulum (ER) stress and kill renal cancer cells effectively. The combination of belinostat and ritonavir induced drastic apoptosis and inhibited the growth of renal cancer cells synergistically. Mechanistically, the combination caused ER stress (evidenced by the increased expression of the ER stress markers) and also enhanced histone acetylation by decreasing the expression of HDACs. To our knowledge, this is the first study that showed a beneficial combined effect of belinostat and ritonavir in renal cancer cells, providing a framework for testing the combination in renal cancer patients.
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spelling pubmed-78386852021-02-16 Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells Isono, Makoto Sato, Akinori Okubo, Kazuki Asano, Takako Asano, Tomohiko Oncol Res Article The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only increases unfolded proteins by suppressing HSP90 but also acts as a proteasome inhibitor. We thought that belinostat and ritonavir together would induce endoplasmic reticulum (ER) stress and kill renal cancer cells effectively. The combination of belinostat and ritonavir induced drastic apoptosis and inhibited the growth of renal cancer cells synergistically. Mechanistically, the combination caused ER stress (evidenced by the increased expression of the ER stress markers) and also enhanced histone acetylation by decreasing the expression of HDACs. To our knowledge, this is the first study that showed a beneficial combined effect of belinostat and ritonavir in renal cancer cells, providing a framework for testing the combination in renal cancer patients. Cognizant Communication Corporation 2016-09-14 /pmc/articles/PMC7838685/ /pubmed/27712589 http://dx.doi.org/10.3727/096504016X14666990347635 Text en Copyright © 2016 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Isono, Makoto
Sato, Akinori
Okubo, Kazuki
Asano, Takako
Asano, Tomohiko
Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells
title Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells
title_full Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells
title_fullStr Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells
title_full_unstemmed Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells
title_short Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells
title_sort ritonavir interacts with belinostat to cause endoplasmic reticulum stress and histone acetylation in renal cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838685/
https://www.ncbi.nlm.nih.gov/pubmed/27712589
http://dx.doi.org/10.3727/096504016X14666990347635
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