Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells

The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cance...

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Autores principales: Tai, Sheng, Xu, Lingfan, Xu, Ming, Zhang, Ligang, Zhang, Yangyang, Zhang, Kaipin, Zhang, Li, Liang, Chaozhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355258/
https://www.ncbi.nlm.nih.gov/pubmed/28061438
http://dx.doi.org/10.18632/oncotarget.14493
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author Tai, Sheng
Xu, Lingfan
Xu, Ming
Zhang, Ligang
Zhang, Yangyang
Zhang, Kaipin
Zhang, Li
Liang, Chaozhao
author_facet Tai, Sheng
Xu, Lingfan
Xu, Ming
Zhang, Ligang
Zhang, Yangyang
Zhang, Kaipin
Zhang, Li
Liang, Chaozhao
author_sort Tai, Sheng
collection PubMed
description The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2. Rad001 and ATO also can synergistically inhibit tumors in prostate cancer xenograft animal model. These results identify and validate a novel mechanism to enhance and expand the existing targeted therapeutic agent to treat prostate cancer.
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spelling pubmed-53552582017-04-26 Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells Tai, Sheng Xu, Lingfan Xu, Ming Zhang, Ligang Zhang, Yangyang Zhang, Kaipin Zhang, Li Liang, Chaozhao Oncotarget Research Paper The inhibitor of PI3K-AKT-mTOR pathway, such as Rad001, has not shown therapeutic efficacy as a single agent in prostate cancer. Arsenic trioxide induces the autophagic pathway in prostate cancer cells. We identified Arsenic trioxide can synergize with Rad001 to induce cytotoxicity of prostate cancer cells. Moreover, we identified synergistic induction of autophagy and apoptosis as the underlying mechanism. This enhanced autophagic cell death is accompanied by increased Beclin1 mRNA stability as well as upregulation of ATG5-ATG12 conjugate, Beclin1, and LC3-2. Rad001 and ATO also can synergistically inhibit tumors in prostate cancer xenograft animal model. These results identify and validate a novel mechanism to enhance and expand the existing targeted therapeutic agent to treat prostate cancer. Impact Journals LLC 2017-01-04 /pmc/articles/PMC5355258/ /pubmed/28061438 http://dx.doi.org/10.18632/oncotarget.14493 Text en Copyright: © 2017 Tai et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Tai, Sheng
Xu, Lingfan
Xu, Ming
Zhang, Ligang
Zhang, Yangyang
Zhang, Kaipin
Zhang, Li
Liang, Chaozhao
Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells
title Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells
title_full Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells
title_fullStr Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells
title_full_unstemmed Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells
title_short Combination of Arsenic trioxide and Everolimus (Rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells
title_sort combination of arsenic trioxide and everolimus (rad001) synergistically induces both autophagy and apoptosis in prostate cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355258/
https://www.ncbi.nlm.nih.gov/pubmed/28061438
http://dx.doi.org/10.18632/oncotarget.14493
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