Cargando…

Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation

The NF-κB signaling pathway plays a pivotal role in regulating the immune response and inflammation. However, it has been shown that NF-κB also has a major role in oncogenesis. Therefore, NF-κB inhibitors have been considered as potential drugs against cancer. Herein, we searched for NF-κB inhibitor...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Zhe, Li, Ming Yue, Mi, Chunliu, Wang, Ke Si, Ma, Juan, Jin, Xuejun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578011/
https://www.ncbi.nlm.nih.gov/pubmed/28933726
http://dx.doi.org/10.3390/ijms18081619
_version_ 1783260448030720000
author Wang, Zhe
Li, Ming Yue
Mi, Chunliu
Wang, Ke Si
Ma, Juan
Jin, Xuejun
author_facet Wang, Zhe
Li, Ming Yue
Mi, Chunliu
Wang, Ke Si
Ma, Juan
Jin, Xuejun
author_sort Wang, Zhe
collection PubMed
description The NF-κB signaling pathway plays a pivotal role in regulating the immune response and inflammation. However, it has been shown that NF-κB also has a major role in oncogenesis. Therefore, NF-κB inhibitors have been considered as potential drugs against cancer. Herein, we searched for NF-κB inhibitors from natural sources and identified mollugin from the roots of Rubia cordifolia L. as an inhibitor of NF-κB activation. We found that mollugin significantly inhibited the expression of an NF-κB reporter gene induced by tumor necrosis factor (TNF)-α in a dose-dependent manner. Moreover, mollugin inhibited TNF-α-induced phosphorylation and nuclear translocation of p65, phosphorylation and degradation of inhibitor of κB (IκBα), and IκB kinase (IKK) phosphorylation. Furthermore, we discovered that pretreatment of cells with mollugin prevented the TNF-α-induced expression of NF-κB target genes, such as genes related to proliferation (COX-2, Cyclin D1 and c-Myc), anti-apoptosis (Bcl-2, cIAP-1 and survivin), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). We also demonstrated that mollugin potentiated TNF-α-induced apoptosis and inhibited proliferation of HeLa cells. We further demonstrated in vivo that mollugin suppressed the growth of tumor xenografts derived from HeLa cells. Taken together, mollugin may be a valuable candidate for cancer treatment by targeting NF-κB.
format Online
Article
Text
id pubmed-5578011
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-55780112017-09-05 Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation Wang, Zhe Li, Ming Yue Mi, Chunliu Wang, Ke Si Ma, Juan Jin, Xuejun Int J Mol Sci Article The NF-κB signaling pathway plays a pivotal role in regulating the immune response and inflammation. However, it has been shown that NF-κB also has a major role in oncogenesis. Therefore, NF-κB inhibitors have been considered as potential drugs against cancer. Herein, we searched for NF-κB inhibitors from natural sources and identified mollugin from the roots of Rubia cordifolia L. as an inhibitor of NF-κB activation. We found that mollugin significantly inhibited the expression of an NF-κB reporter gene induced by tumor necrosis factor (TNF)-α in a dose-dependent manner. Moreover, mollugin inhibited TNF-α-induced phosphorylation and nuclear translocation of p65, phosphorylation and degradation of inhibitor of κB (IκBα), and IκB kinase (IKK) phosphorylation. Furthermore, we discovered that pretreatment of cells with mollugin prevented the TNF-α-induced expression of NF-κB target genes, such as genes related to proliferation (COX-2, Cyclin D1 and c-Myc), anti-apoptosis (Bcl-2, cIAP-1 and survivin), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). We also demonstrated that mollugin potentiated TNF-α-induced apoptosis and inhibited proliferation of HeLa cells. We further demonstrated in vivo that mollugin suppressed the growth of tumor xenografts derived from HeLa cells. Taken together, mollugin may be a valuable candidate for cancer treatment by targeting NF-κB. MDPI 2017-07-26 /pmc/articles/PMC5578011/ /pubmed/28933726 http://dx.doi.org/10.3390/ijms18081619 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Zhe
Li, Ming Yue
Mi, Chunliu
Wang, Ke Si
Ma, Juan
Jin, Xuejun
Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation
title Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation
title_full Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation
title_fullStr Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation
title_full_unstemmed Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation
title_short Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation
title_sort mollugin has an anti-cancer therapeutic effect by inhibiting tnf-α-induced nf-κb activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578011/
https://www.ncbi.nlm.nih.gov/pubmed/28933726
http://dx.doi.org/10.3390/ijms18081619
work_keys_str_mv AT wangzhe molluginhasananticancertherapeuticeffectbyinhibitingtnfainducednfkbactivation
AT limingyue molluginhasananticancertherapeuticeffectbyinhibitingtnfainducednfkbactivation
AT michunliu molluginhasananticancertherapeuticeffectbyinhibitingtnfainducednfkbactivation
AT wangkesi molluginhasananticancertherapeuticeffectbyinhibitingtnfainducednfkbactivation
AT majuan molluginhasananticancertherapeuticeffectbyinhibitingtnfainducednfkbactivation
AT jinxuejun molluginhasananticancertherapeuticeffectbyinhibitingtnfainducednfkbactivation