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Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells

Previous studies have demonstrated that the chronic administration of valproic acid (VPA) suppresses angiogenesis in vivo; however, the mechanisms implicated in VPA-induced autophagy remain unclear. The current study aimed to assess VPA-induced autophagy in three prostate cancer cell lines (PC3, DU1...

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Autores principales: Xia, Qinghua, Zheng, Yi, Jiang, Wei, Huang, Zhongxian, Wang, Muwen, Rodriguez, Ronald, Jin, Xunbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998110/
https://www.ncbi.nlm.nih.gov/pubmed/27588130
http://dx.doi.org/10.3892/ol.2016.4880
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author Xia, Qinghua
Zheng, Yi
Jiang, Wei
Huang, Zhongxian
Wang, Muwen
Rodriguez, Ronald
Jin, Xunbo
author_facet Xia, Qinghua
Zheng, Yi
Jiang, Wei
Huang, Zhongxian
Wang, Muwen
Rodriguez, Ronald
Jin, Xunbo
author_sort Xia, Qinghua
collection PubMed
description Previous studies have demonstrated that the chronic administration of valproic acid (VPA) suppresses angiogenesis in vivo; however, the mechanisms implicated in VPA-induced autophagy remain unclear. The current study aimed to assess VPA-induced autophagy in three prostate cancer cell lines (PC3, DU145 and LNCaP), in addition to analyzing the Akt/mammalian target of rapamycin (mTOR) signal pathway. Prostate cancer cell lines were cultured with various doses of VPA. Cell cycle was analyzed using flow cytometry, and autophagy markers [1A/1B-light chain 3 (LC3)-II and Beclin-1] were examined using transmission electron microscopy, fluorescent microscopy and western blotting. Activation of the Akt/mTOR signal pathway was also assessed by western blotting. The results demonstrated that VPA induced autophagosomes and suppressed the Akt/mTOR signal pathway. This was confirmed by detection of increased LC3-II and Beclin-1 in VPA-treated cells compared with untreated controls. Phosphorylated forms of Akt (PC3, P=0.048; DU145, P=0.045; LNCaP, P=0.039) and mTOR (PC3, P=0.012; DU145, P=0.41; LNCaP, P=0.35) were significantly reduced following VPA treatment. These results suggest that VPA may function as a histone deacetylase inhibitor, suppressing the growth of prostate cancer cells by modulating autophagy pathways, including inhibition of the Akt/mTOR pathway. Further experiments are required to determine the significance of all involved pathways regarding VPA-induced growth inhibition.
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spelling pubmed-49981102016-09-01 Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells Xia, Qinghua Zheng, Yi Jiang, Wei Huang, Zhongxian Wang, Muwen Rodriguez, Ronald Jin, Xunbo Oncol Lett Articles Previous studies have demonstrated that the chronic administration of valproic acid (VPA) suppresses angiogenesis in vivo; however, the mechanisms implicated in VPA-induced autophagy remain unclear. The current study aimed to assess VPA-induced autophagy in three prostate cancer cell lines (PC3, DU145 and LNCaP), in addition to analyzing the Akt/mammalian target of rapamycin (mTOR) signal pathway. Prostate cancer cell lines were cultured with various doses of VPA. Cell cycle was analyzed using flow cytometry, and autophagy markers [1A/1B-light chain 3 (LC3)-II and Beclin-1] were examined using transmission electron microscopy, fluorescent microscopy and western blotting. Activation of the Akt/mTOR signal pathway was also assessed by western blotting. The results demonstrated that VPA induced autophagosomes and suppressed the Akt/mTOR signal pathway. This was confirmed by detection of increased LC3-II and Beclin-1 in VPA-treated cells compared with untreated controls. Phosphorylated forms of Akt (PC3, P=0.048; DU145, P=0.045; LNCaP, P=0.039) and mTOR (PC3, P=0.012; DU145, P=0.41; LNCaP, P=0.35) were significantly reduced following VPA treatment. These results suggest that VPA may function as a histone deacetylase inhibitor, suppressing the growth of prostate cancer cells by modulating autophagy pathways, including inhibition of the Akt/mTOR pathway. Further experiments are required to determine the significance of all involved pathways regarding VPA-induced growth inhibition. D.A. Spandidos 2016-09 2016-07-18 /pmc/articles/PMC4998110/ /pubmed/27588130 http://dx.doi.org/10.3892/ol.2016.4880 Text en Copyright: © Xia et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Xia, Qinghua
Zheng, Yi
Jiang, Wei
Huang, Zhongxian
Wang, Muwen
Rodriguez, Ronald
Jin, Xunbo
Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells
title Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells
title_full Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells
title_fullStr Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells
title_full_unstemmed Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells
title_short Valproic acid induces autophagy by suppressing the Akt/mTOR pathway in human prostate cancer cells
title_sort valproic acid induces autophagy by suppressing the akt/mtor pathway in human prostate cancer cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998110/
https://www.ncbi.nlm.nih.gov/pubmed/27588130
http://dx.doi.org/10.3892/ol.2016.4880
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