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Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity

Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and...

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Autores principales: Deep, Gagan, Kumar, Rahul, Jain, Anil K., Dhar, Deepanshi, Panigrahi, Gati K., Hussain, Anowar, Agarwal, Chapla, El-Elimat, Tamam, Sica, Vincent P., Oberlies, Nicholas H., Agarwal, Rajesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793251/
https://www.ncbi.nlm.nih.gov/pubmed/26979487
http://dx.doi.org/10.1038/srep23135
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author Deep, Gagan
Kumar, Rahul
Jain, Anil K.
Dhar, Deepanshi
Panigrahi, Gati K.
Hussain, Anowar
Agarwal, Chapla
El-Elimat, Tamam
Sica, Vincent P.
Oberlies, Nicholas H.
Agarwal, Rajesh
author_facet Deep, Gagan
Kumar, Rahul
Jain, Anil K.
Dhar, Deepanshi
Panigrahi, Gati K.
Hussain, Anowar
Agarwal, Chapla
El-Elimat, Tamam
Sica, Vincent P.
Oberlies, Nicholas H.
Agarwal, Rajesh
author_sort Deep, Gagan
collection PubMed
description Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1–5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47(phox)). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity.
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spelling pubmed-47932512016-03-16 Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity Deep, Gagan Kumar, Rahul Jain, Anil K. Dhar, Deepanshi Panigrahi, Gati K. Hussain, Anowar Agarwal, Chapla El-Elimat, Tamam Sica, Vincent P. Oberlies, Nicholas H. Agarwal, Rajesh Sci Rep Article Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1–5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47(phox)). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity. Nature Publishing Group 2016-03-16 /pmc/articles/PMC4793251/ /pubmed/26979487 http://dx.doi.org/10.1038/srep23135 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Deep, Gagan
Kumar, Rahul
Jain, Anil K.
Dhar, Deepanshi
Panigrahi, Gati K.
Hussain, Anowar
Agarwal, Chapla
El-Elimat, Tamam
Sica, Vincent P.
Oberlies, Nicholas H.
Agarwal, Rajesh
Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity
title Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity
title_full Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity
title_fullStr Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity
title_full_unstemmed Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity
title_short Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity
title_sort graviola inhibits hypoxia-induced nadph oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4793251/
https://www.ncbi.nlm.nih.gov/pubmed/26979487
http://dx.doi.org/10.1038/srep23135
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