Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

<h4>Background</h4>We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-tr...

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Autores principales:	Azhar R Hussain, Shahab Uddin, Rong Bu, Omar S Khan, Saeeda O Ahmed, Maqbool Ahmed, Khawla S Al-Kuraya
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07d26e01214c4ad9a8c821ce8c34d555
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spelling	oai:doaj.org-article:07d26e01214c4ad9a8c821ce8c34d5552021-11-04T06:08:48ZResveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.1932-620310.1371/journal.pone.0024703https://doaj.org/article/07d26e01214c4ad9a8c821ce8c34d5552011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21931821/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis.<h4>Methodology/principal findings</h4>We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect.<h4>Conclusion/significance</h4>Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.Azhar R HussainShahab UddinRong BuOmar S KhanSaeeda O AhmedMaqbool AhmedKhawla S Al-KurayaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 9, p e24703 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Azhar R Hussain Shahab Uddin Rong Bu Omar S Khan Saeeda O Ahmed Maqbool Ahmed Khawla S Al-Kuraya Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
description	<h4>Background</h4>We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis.<h4>Methodology/principal findings</h4>We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect.<h4>Conclusion/significance</h4>Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.
format	article
author	Azhar R Hussain Shahab Uddin Rong Bu Omar S Khan Saeeda O Ahmed Maqbool Ahmed Khawla S Al-Kuraya
author_facet	Azhar R Hussain Shahab Uddin Rong Bu Omar S Khan Saeeda O Ahmed Maqbool Ahmed Khawla S Al-Kuraya
author_sort	Azhar R Hussain
title	Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
title_short	Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
title_full	Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
title_fullStr	Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
title_full_unstemmed	Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
title_sort	resveratrol suppresses constitutive activation of akt via generation of ros and induces apoptosis in diffuse large b cell lymphoma cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/07d26e01214c4ad9a8c821ce8c34d555
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Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

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