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Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma

Despite great advancements in the treatment of non-Hodgkin lymphoma (NHL), sensitivity of different subtypes to therapy varies. Targeting the aberrant activation NF-κB signaling pathways in lymphoid malignancies is a promising strategy. Here, we report that 11(13)-dehydroivaxillin (DHI), a natural c...

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Autores principales: Xiao, Xinhua, Li, Huiliang, Jin, Huizi, Jin, Jin, Yu, Miao, Ma, Chunmin, Tong, Yin, Zhou, Li, Lei, Hu, Xu, Hanzhang, Zhang, Weidong, Liu, Wei, Wu, Yingli
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636986/
https://www.ncbi.nlm.nih.gov/pubmed/28906487
http://dx.doi.org/10.1038/cddis.2017.442
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author Xiao, Xinhua
Li, Huiliang
Jin, Huizi
Jin, Jin
Yu, Miao
Ma, Chunmin
Tong, Yin
Zhou, Li
Lei, Hu
Xu, Hanzhang
Zhang, Weidong
Liu, Wei
Wu, Yingli
author_facet Xiao, Xinhua
Li, Huiliang
Jin, Huizi
Jin, Jin
Yu, Miao
Ma, Chunmin
Tong, Yin
Zhou, Li
Lei, Hu
Xu, Hanzhang
Zhang, Weidong
Liu, Wei
Wu, Yingli
author_sort Xiao, Xinhua
collection PubMed
description Despite great advancements in the treatment of non-Hodgkin lymphoma (NHL), sensitivity of different subtypes to therapy varies. Targeting the aberrant activation NF-κB signaling pathways in lymphoid malignancies is a promising strategy. Here, we report that 11(13)-dehydroivaxillin (DHI), a natural compound isolated from the Carpesium genus, induces growth inhibition and apoptosis of NHL cells. Multiple signaling cascades are influenced by DHI in NHL cells. PI3K/AKT and ERK are activated or inhibited in a cell type dependent manner, whereas NF-κB signaling pathway was inhibited in all the NHL cells tested. Applying the cellular thermal shift assay, we further demonstrated that DHI directly interacts with IKKα/IKKβ in NHL cells. Interestingly, DHI treatment also reduced the IKKα/IKKβ protein level in NHL cells. Consistent with this finding, knockdown of IKKα/IKKβ inhibits cell proliferation and enhances DHI-induced proliferation inhibition. Overexpression of p65, p52 or RelB partially reverses DHI-induced cell growth inhibition. Furthermore, DHI treatment significantly inhibits the growth of NHL cell xenografts. In conclusion, we demonstrate that DHI exerts anti-NHL effect in vitro and in vivo, through a cumulative effect on NF-κB and other pathways. DHI may serve as a promising lead compound for the therapy of NHL.
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spelling pubmed-56369862017-10-12 Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma Xiao, Xinhua Li, Huiliang Jin, Huizi Jin, Jin Yu, Miao Ma, Chunmin Tong, Yin Zhou, Li Lei, Hu Xu, Hanzhang Zhang, Weidong Liu, Wei Wu, Yingli Cell Death Dis Original Article Despite great advancements in the treatment of non-Hodgkin lymphoma (NHL), sensitivity of different subtypes to therapy varies. Targeting the aberrant activation NF-κB signaling pathways in lymphoid malignancies is a promising strategy. Here, we report that 11(13)-dehydroivaxillin (DHI), a natural compound isolated from the Carpesium genus, induces growth inhibition and apoptosis of NHL cells. Multiple signaling cascades are influenced by DHI in NHL cells. PI3K/AKT and ERK are activated or inhibited in a cell type dependent manner, whereas NF-κB signaling pathway was inhibited in all the NHL cells tested. Applying the cellular thermal shift assay, we further demonstrated that DHI directly interacts with IKKα/IKKβ in NHL cells. Interestingly, DHI treatment also reduced the IKKα/IKKβ protein level in NHL cells. Consistent with this finding, knockdown of IKKα/IKKβ inhibits cell proliferation and enhances DHI-induced proliferation inhibition. Overexpression of p65, p52 or RelB partially reverses DHI-induced cell growth inhibition. Furthermore, DHI treatment significantly inhibits the growth of NHL cell xenografts. In conclusion, we demonstrate that DHI exerts anti-NHL effect in vitro and in vivo, through a cumulative effect on NF-κB and other pathways. DHI may serve as a promising lead compound for the therapy of NHL. Nature Publishing Group 2017-09 2017-09-14 /pmc/articles/PMC5636986/ /pubmed/28906487 http://dx.doi.org/10.1038/cddis.2017.442 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. 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 Original Article
Xiao, Xinhua
Li, Huiliang
Jin, Huizi
Jin, Jin
Yu, Miao
Ma, Chunmin
Tong, Yin
Zhou, Li
Lei, Hu
Xu, Hanzhang
Zhang, Weidong
Liu, Wei
Wu, Yingli
Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
title Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
title_full Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
title_fullStr Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
title_full_unstemmed Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
title_short Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
title_sort identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-hodgkin's lymphoma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5636986/
https://www.ncbi.nlm.nih.gov/pubmed/28906487
http://dx.doi.org/10.1038/cddis.2017.442
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