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Identification and validation of p50 as the cellular target of eriocalyxin B

As an ent-kaurene diterpenoid isolated from Isodon eriocalyx var. Laxiflora, Eriocalyxin B (EriB) possesses potent bioactivity of antitumor and anti-autoimmune inflammation, which has been suggested to work through inhibition of NF-kappaB (NF-κB) signaling. However, the direct target of EriB remains...

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Autores principales: Kong, Ling-Mei, Deng, Xu, Zuo, Zhi-Li, Sun, Han-Dong, Zhao, Qin-Shi, Li, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294364/
https://www.ncbi.nlm.nih.gov/pubmed/25404639
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author Kong, Ling-Mei
Deng, Xu
Zuo, Zhi-Li
Sun, Han-Dong
Zhao, Qin-Shi
Li, Yan
author_facet Kong, Ling-Mei
Deng, Xu
Zuo, Zhi-Li
Sun, Han-Dong
Zhao, Qin-Shi
Li, Yan
author_sort Kong, Ling-Mei
collection PubMed
description As an ent-kaurene diterpenoid isolated from Isodon eriocalyx var. Laxiflora, Eriocalyxin B (EriB) possesses potent bioactivity of antitumor and anti-autoimmune inflammation, which has been suggested to work through inhibition of NF-kappaB (NF-κB) signaling. However, the direct target of EriB remains elusive. In this study, we showed that EriB induced apoptosis is associated with the inhibition of NF-κB signaling in SMMC-7721 hepatocellular carcinoma cells. With activity-based probe profiling, we identified p50 protein as the direct target of EriB. We showed that cysteine 62 is the critical residue of p50 for EriB binding through the α, β-unsaturated ketones. As the result, EriB selectively blocks the binding between p50 and the response elements, whereas having no effect on the dimerization or the nuclear translocation of p50 and p65. SiRNA mediated knockdown of p50 attenuated the apoptosis induced by EriB in SMMC-7721 cells. Taken together, our studies illustrated that EriB induces cancer cell apoptosis through interfering with the binding between NF-κB and the response elements by targeting the cysteine 62 of p50, which highlights its potential for the development of p50 targeted cancer therapeutic agents.
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spelling pubmed-42943642015-01-21 Identification and validation of p50 as the cellular target of eriocalyxin B Kong, Ling-Mei Deng, Xu Zuo, Zhi-Li Sun, Han-Dong Zhao, Qin-Shi Li, Yan Oncotarget Research Paper As an ent-kaurene diterpenoid isolated from Isodon eriocalyx var. Laxiflora, Eriocalyxin B (EriB) possesses potent bioactivity of antitumor and anti-autoimmune inflammation, which has been suggested to work through inhibition of NF-kappaB (NF-κB) signaling. However, the direct target of EriB remains elusive. In this study, we showed that EriB induced apoptosis is associated with the inhibition of NF-κB signaling in SMMC-7721 hepatocellular carcinoma cells. With activity-based probe profiling, we identified p50 protein as the direct target of EriB. We showed that cysteine 62 is the critical residue of p50 for EriB binding through the α, β-unsaturated ketones. As the result, EriB selectively blocks the binding between p50 and the response elements, whereas having no effect on the dimerization or the nuclear translocation of p50 and p65. SiRNA mediated knockdown of p50 attenuated the apoptosis induced by EriB in SMMC-7721 cells. Taken together, our studies illustrated that EriB induces cancer cell apoptosis through interfering with the binding between NF-κB and the response elements by targeting the cysteine 62 of p50, which highlights its potential for the development of p50 targeted cancer therapeutic agents. Impact Journals LLC 2014-10-24 /pmc/articles/PMC4294364/ /pubmed/25404639 Text en Copyright: © 2014 Kong et al. http://creativecommons.org/licenses/by/2.5/ 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
Kong, Ling-Mei
Deng, Xu
Zuo, Zhi-Li
Sun, Han-Dong
Zhao, Qin-Shi
Li, Yan
Identification and validation of p50 as the cellular target of eriocalyxin B
title Identification and validation of p50 as the cellular target of eriocalyxin B
title_full Identification and validation of p50 as the cellular target of eriocalyxin B
title_fullStr Identification and validation of p50 as the cellular target of eriocalyxin B
title_full_unstemmed Identification and validation of p50 as the cellular target of eriocalyxin B
title_short Identification and validation of p50 as the cellular target of eriocalyxin B
title_sort identification and validation of p50 as the cellular target of eriocalyxin b
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294364/
https://www.ncbi.nlm.nih.gov/pubmed/25404639
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