Cargando…

Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma

Von Hippel-Lindau (VHL) syndrome is a rare inherited cancer disease where the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HBs), CNS-HBs, and clear cell renal cell carcinoma (ccRCC). Since standard therapies in VHL have shown limited respons...

Descripción completa

Detalles Bibliográficos
Autores principales: Albiñana, Virginia, Recio-Poveda, Lucía, González-Peramato, Pilar, Martinez-Piñeiro, Luis, Botella, Luisa María, Cuesta, Angel M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835934/
https://www.ncbi.nlm.nih.gov/pubmed/35163250
http://dx.doi.org/10.3390/ijms23031325
_version_ 1784649554244665344
author Albiñana, Virginia
Recio-Poveda, Lucía
González-Peramato, Pilar
Martinez-Piñeiro, Luis
Botella, Luisa María
Cuesta, Angel M.
author_facet Albiñana, Virginia
Recio-Poveda, Lucía
González-Peramato, Pilar
Martinez-Piñeiro, Luis
Botella, Luisa María
Cuesta, Angel M.
author_sort Albiñana, Virginia
collection PubMed
description Von Hippel-Lindau (VHL) syndrome is a rare inherited cancer disease where the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HBs), CNS-HBs, and clear cell renal cell carcinoma (ccRCC). Since standard therapies in VHL have shown limited response, leaving surgery as the only possible treatment, targeting of the β2-adrenergic receptor (ADRB2) has shown therapeutic antitumor benefits on VHL-retinal HBs (clinical trial), VHL-CNS HBs, and VHL-ccRCC (in vitro and in vivo). In the present study, we wanted to look deep into the effects of the ADRB2 blockers propranolol and ICI-118,551 on two main aspects of cancer progression: (i) the changes on the inflammatory response of ccRCC cells; and (ii) the modulation on the Warburg effect (glycolytic metabolism), concretely, on the expression of genes involved in the cell reactive oxygen species (ROS) balance and levels. Accordingly, in vitro studies with primary VHL-ccRCC and 786-O cells measuring ROS levels, ROS-expression of detoxifying enzymes, and the expression of p65/NF-κB targets by RT-PCR were carried out. Furthermore, histological analyses of ccRCC samples from heterotopic mouse xenografts were performed. The obtained results show that ADRB2 blockade in ccRCC cells reduces the level of oxidative stress and stabilizes the inflammatory response. Thus, these data further support the idea of targeting ADRB2 as a promising strategy for the treatment of VHL and other non-VHL tumors.
format Online
Article
Text
id pubmed-8835934
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-88359342022-02-12 Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma Albiñana, Virginia Recio-Poveda, Lucía González-Peramato, Pilar Martinez-Piñeiro, Luis Botella, Luisa María Cuesta, Angel M. Int J Mol Sci Article Von Hippel-Lindau (VHL) syndrome is a rare inherited cancer disease where the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HBs), CNS-HBs, and clear cell renal cell carcinoma (ccRCC). Since standard therapies in VHL have shown limited response, leaving surgery as the only possible treatment, targeting of the β2-adrenergic receptor (ADRB2) has shown therapeutic antitumor benefits on VHL-retinal HBs (clinical trial), VHL-CNS HBs, and VHL-ccRCC (in vitro and in vivo). In the present study, we wanted to look deep into the effects of the ADRB2 blockers propranolol and ICI-118,551 on two main aspects of cancer progression: (i) the changes on the inflammatory response of ccRCC cells; and (ii) the modulation on the Warburg effect (glycolytic metabolism), concretely, on the expression of genes involved in the cell reactive oxygen species (ROS) balance and levels. Accordingly, in vitro studies with primary VHL-ccRCC and 786-O cells measuring ROS levels, ROS-expression of detoxifying enzymes, and the expression of p65/NF-κB targets by RT-PCR were carried out. Furthermore, histological analyses of ccRCC samples from heterotopic mouse xenografts were performed. The obtained results show that ADRB2 blockade in ccRCC cells reduces the level of oxidative stress and stabilizes the inflammatory response. Thus, these data further support the idea of targeting ADRB2 as a promising strategy for the treatment of VHL and other non-VHL tumors. MDPI 2022-01-25 /pmc/articles/PMC8835934/ /pubmed/35163250 http://dx.doi.org/10.3390/ijms23031325 Text en © 2022 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
Albiñana, Virginia
Recio-Poveda, Lucía
González-Peramato, Pilar
Martinez-Piñeiro, Luis
Botella, Luisa María
Cuesta, Angel M.
Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma
title Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma
title_full Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma
title_fullStr Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma
title_full_unstemmed Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma
title_short Blockade of β2-Adrenergic Receptor Reduces Inflammation and Oxidative Stress in Clear Cell Renal Cell Carcinoma
title_sort blockade of β2-adrenergic receptor reduces inflammation and oxidative stress in clear cell renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835934/
https://www.ncbi.nlm.nih.gov/pubmed/35163250
http://dx.doi.org/10.3390/ijms23031325
work_keys_str_mv AT albinanavirginia blockadeofb2adrenergicreceptorreducesinflammationandoxidativestressinclearcellrenalcellcarcinoma
AT reciopovedalucia blockadeofb2adrenergicreceptorreducesinflammationandoxidativestressinclearcellrenalcellcarcinoma
AT gonzalezperamatopilar blockadeofb2adrenergicreceptorreducesinflammationandoxidativestressinclearcellrenalcellcarcinoma
AT martinezpineiroluis blockadeofb2adrenergicreceptorreducesinflammationandoxidativestressinclearcellrenalcellcarcinoma
AT botellaluisamaria blockadeofb2adrenergicreceptorreducesinflammationandoxidativestressinclearcellrenalcellcarcinoma
AT cuestaangelm blockadeofb2adrenergicreceptorreducesinflammationandoxidativestressinclearcellrenalcellcarcinoma