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Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer

Inflammation, by inducing a tumor-promoting microenvironment, is a hallmark for prostate cancer (PCa) progression. NOD-like receptor protein 3 (NLRP3)-inflammasome activation, interleukin-1β (IL-1β) secretion, and cancer cell-released extracellular vesicles (EVs) contribute to the establishment of t...

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Autores principales: Mezzasoma, Letizia, Talesa, Vincenzo Nicola, Costanzi, Egidia, Bellezza, Ilaria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228623/
https://www.ncbi.nlm.nih.gov/pubmed/34070682
http://dx.doi.org/10.3390/biom11060794
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author Mezzasoma, Letizia
Talesa, Vincenzo Nicola
Costanzi, Egidia
Bellezza, Ilaria
author_facet Mezzasoma, Letizia
Talesa, Vincenzo Nicola
Costanzi, Egidia
Bellezza, Ilaria
author_sort Mezzasoma, Letizia
collection PubMed
description Inflammation, by inducing a tumor-promoting microenvironment, is a hallmark for prostate cancer (PCa) progression. NOD-like receptor protein 3 (NLRP3)-inflammasome activation, interleukin-1β (IL-1β) secretion, and cancer cell-released extracellular vesicles (EVs) contribute to the establishment of tumor microenvironment. We have shown that PC3-derived EVs (PC3-EVs) activate inflammasome cascade in non-cancerous PNT2 cells. It is known that the endogenous biomolecules and Natriuretic Peptides (NPs), such as ANP and BNP, inhibit inflammasome activation in immune cells. Here we investigated whether ANP and BNP modify PCa inflammatory phenotype in vitro. By using PNT2, LNCaP, and PC3 cell lines, which model different PCa progression stages, we analyzed inflammasome activation and the related pathways by Western blot and IL-1β secretion by ELISA. We found that tumor progression is characterized by constitutive inflammasome activation, increased IL-1β secretion, and reduced endogenous NPs expression. The administration of exogenous ANP and BNP, via p38-MAPK or ERK1/2-MAPK, by inducing NLRP3 phosphorylation, counteract inflammasome activation and IL-1β maturation in PC3 and PC3-EVs-treated PNT2 cells, respectively. Our results demonstrate that NPs, by interfering with cell-specific signaling pathways, exert pleiotropic anti-inflammatory effects converging toward inflammasome phosphorylation and suggest that NPs can be included in a drug repurposing process for PCa.
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spelling pubmed-82286232021-06-26 Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer Mezzasoma, Letizia Talesa, Vincenzo Nicola Costanzi, Egidia Bellezza, Ilaria Biomolecules Article Inflammation, by inducing a tumor-promoting microenvironment, is a hallmark for prostate cancer (PCa) progression. NOD-like receptor protein 3 (NLRP3)-inflammasome activation, interleukin-1β (IL-1β) secretion, and cancer cell-released extracellular vesicles (EVs) contribute to the establishment of tumor microenvironment. We have shown that PC3-derived EVs (PC3-EVs) activate inflammasome cascade in non-cancerous PNT2 cells. It is known that the endogenous biomolecules and Natriuretic Peptides (NPs), such as ANP and BNP, inhibit inflammasome activation in immune cells. Here we investigated whether ANP and BNP modify PCa inflammatory phenotype in vitro. By using PNT2, LNCaP, and PC3 cell lines, which model different PCa progression stages, we analyzed inflammasome activation and the related pathways by Western blot and IL-1β secretion by ELISA. We found that tumor progression is characterized by constitutive inflammasome activation, increased IL-1β secretion, and reduced endogenous NPs expression. The administration of exogenous ANP and BNP, via p38-MAPK or ERK1/2-MAPK, by inducing NLRP3 phosphorylation, counteract inflammasome activation and IL-1β maturation in PC3 and PC3-EVs-treated PNT2 cells, respectively. Our results demonstrate that NPs, by interfering with cell-specific signaling pathways, exert pleiotropic anti-inflammatory effects converging toward inflammasome phosphorylation and suggest that NPs can be included in a drug repurposing process for PCa. MDPI 2021-05-25 /pmc/articles/PMC8228623/ /pubmed/34070682 http://dx.doi.org/10.3390/biom11060794 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mezzasoma, Letizia
Talesa, Vincenzo Nicola
Costanzi, Egidia
Bellezza, Ilaria
Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
title Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
title_full Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
title_fullStr Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
title_full_unstemmed Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
title_short Natriuretic Peptides Regulate Prostate Cells Inflammatory Behavior: Potential Novel Anticancer Agents for Prostate Cancer
title_sort natriuretic peptides regulate prostate cells inflammatory behavior: potential novel anticancer agents for prostate cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228623/
https://www.ncbi.nlm.nih.gov/pubmed/34070682
http://dx.doi.org/10.3390/biom11060794
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