Cargando…

Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells

Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFα plays a central orchestrating role. TNFα acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2). These proteins direct inward infiltration/migration of tumor-asso...

Descripción completa

Detalles Bibliográficos
Autores principales: Bauer, David, Redmon, Natalie, Mazzio, Elizabeth, Soliman, Karam F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404872/
https://www.ncbi.nlm.nih.gov/pubmed/28441391
http://dx.doi.org/10.1371/journal.pone.0175558
_version_ 1783231665909268480
author Bauer, David
Redmon, Natalie
Mazzio, Elizabeth
Soliman, Karam F.
author_facet Bauer, David
Redmon, Natalie
Mazzio, Elizabeth
Soliman, Karam F.
author_sort Bauer, David
collection PubMed
description Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFα plays a central orchestrating role. TNFα acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2). These proteins direct inward infiltration/migration of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory cells (Tregs), T helper IL-17-producing cells (Th17s), metastasis-associated macrophages (MAMs) and cancer-associated fibroblasts (CAFs). Tumor embedded infiltrates collectively enable immune evasion, tumor growth, angiogenesis, and metastasis. In the current study, we investigate the potential of apigenin, a known anti-inflammatory constituent of parsley, to downregulate TNFα mediated release of chemokines from human triple-negative cells (MDA-MB-231 cells). The results show that TNFα stimulation leads to large rise of CCL2, granulocyte macrophage colony-stimulating factor (GMCSF), IL-1α and IL-6, all suppressed by apigenin. While many aspects of the transcriptome for NFkB signaling were evaluated, the data show signaling patterns associated with CCL2 were blocked by apigenin and mediated through suppressed mRNA and protein synthesis of IKBKe. Moreover, the data show that the attenuation of CCL2 by apigenin in the presence TNFα paralleled the suppression of phosphorylated extracellular signal-regulated kinase 1 (ERK 1/ 2). In summary, the obtained findings suggest that there exists a TNFα evoked release of CCL2 and other LSP recruiting cytokines from human breast cancer cells, which can be attenuated by apigenin.
format Online
Article
Text
id pubmed-5404872
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-54048722017-05-12 Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells Bauer, David Redmon, Natalie Mazzio, Elizabeth Soliman, Karam F. PLoS One Research Article Mortality associated with breast cancer is attributable to aggressive metastasis, to which TNFα plays a central orchestrating role. TNFα acts on breast tumor TNF receptors evoking the release of chemotactic proteins (e.g. MCP-1/CCL2). These proteins direct inward infiltration/migration of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), myeloid-derived suppressor cells (MDSCs), T-regulatory cells (Tregs), T helper IL-17-producing cells (Th17s), metastasis-associated macrophages (MAMs) and cancer-associated fibroblasts (CAFs). Tumor embedded infiltrates collectively enable immune evasion, tumor growth, angiogenesis, and metastasis. In the current study, we investigate the potential of apigenin, a known anti-inflammatory constituent of parsley, to downregulate TNFα mediated release of chemokines from human triple-negative cells (MDA-MB-231 cells). The results show that TNFα stimulation leads to large rise of CCL2, granulocyte macrophage colony-stimulating factor (GMCSF), IL-1α and IL-6, all suppressed by apigenin. While many aspects of the transcriptome for NFkB signaling were evaluated, the data show signaling patterns associated with CCL2 were blocked by apigenin and mediated through suppressed mRNA and protein synthesis of IKBKe. Moreover, the data show that the attenuation of CCL2 by apigenin in the presence TNFα paralleled the suppression of phosphorylated extracellular signal-regulated kinase 1 (ERK 1/ 2). In summary, the obtained findings suggest that there exists a TNFα evoked release of CCL2 and other LSP recruiting cytokines from human breast cancer cells, which can be attenuated by apigenin. Public Library of Science 2017-04-25 /pmc/articles/PMC5404872/ /pubmed/28441391 http://dx.doi.org/10.1371/journal.pone.0175558 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Bauer, David
Redmon, Natalie
Mazzio, Elizabeth
Soliman, Karam F.
Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells
title Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells
title_full Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells
title_fullStr Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells
title_full_unstemmed Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells
title_short Apigenin inhibits TNFα/IL-1α-induced CCL2 release through IKBK-epsilon signaling in MDA-MB-231 human breast cancer cells
title_sort apigenin inhibits tnfα/il-1α-induced ccl2 release through ikbk-epsilon signaling in mda-mb-231 human breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5404872/
https://www.ncbi.nlm.nih.gov/pubmed/28441391
http://dx.doi.org/10.1371/journal.pone.0175558
work_keys_str_mv AT bauerdavid apigenininhibitstnfail1ainducedccl2releasethroughikbkepsilonsignalinginmdamb231humanbreastcancercells
AT redmonnatalie apigenininhibitstnfail1ainducedccl2releasethroughikbkepsilonsignalinginmdamb231humanbreastcancercells
AT mazzioelizabeth apigenininhibitstnfail1ainducedccl2releasethroughikbkepsilonsignalinginmdamb231humanbreastcancercells
AT solimankaramf apigenininhibitstnfail1ainducedccl2releasethroughikbkepsilonsignalinginmdamb231humanbreastcancercells