Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease
Von Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in c...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de documento: | artigo |
| Data de publicação: | 2020 |
| País: | España |
| Recursos: | Universidad Autónoma de Madrid |
| Repositório: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglês |
| OAI Identifier: | oai:repositorio.uam.es:10486/719145 |
| Acesso em linha: | http://hdl.handle.net/10486/719145 https://dx.doi.org/10.3390/jcm9092740 |
| Access Level: | Acceso aberto |
| Palavra-chave: | anticarcinogenic CcRCC HIF ICI-118,551 propranolol VHL β-adrenergic receptor antagonist Medicina |
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Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau diseaseAlbiñana, VirginiaGallardo Vara, Eunatede Rojas P, IsabelRecio Poveda, LuciaAguado, TaniaCanto Cano, AnaAguirre, Daniel T.Serra, Marcelo M.González-Peramato Gutiérrez, María del PilarMartínez Piñeiro, LuisCuesta, Angel M.Botella, Luisa MariaanticarcinogenicCcRCCHIFICI-118,551propranololVHLβ-adrenergic receptor antagonistMedicinaVon Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of β2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL−/− ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumorsThis research was funded by Ministry of Economy and Competitivity, grant number SAF2017-83351-R. L.M-P. was supported by grants from Madrid Regional Government “IMMUNOTHERCAN” [B2017/BMD-3733-2]. A.M.C. was funded by the Spanish Alliance of VHL patients and V.A. was funded by CIBERERMDPIDepartamento de Anatomía PatológicaFacultad de Medicina20202020-08-25research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10486/719145https://dx.doi.org/10.3390/jcm9092740reponame:Biblos-e Archivo. Repositorio Institucional de la UAMinstname:Universidad Autónoma de MadridInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositorio.uam.es:10486/7191452026-06-23T12:46:27Z |
| dc.title.none.fl_str_mv |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease |
| title |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease |
| spellingShingle |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease Albiñana, Virginia anticarcinogenic CcRCC HIF ICI-118,551 propranolol VHL β-adrenergic receptor antagonist Medicina |
| title_short |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease |
| title_full |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease |
| title_fullStr |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease |
| title_full_unstemmed |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease |
| title_sort |
Targeting β2-adrenergic receptors shows therapeutical benefits in clear cell renal cell carcinoma from von Hippel–Lindau disease |
| dc.creator.none.fl_str_mv |
Albiñana, Virginia Gallardo Vara, Eunate de Rojas P, Isabel Recio Poveda, Lucia Aguado, Tania Canto Cano, Ana Aguirre, Daniel T. Serra, Marcelo M. González-Peramato Gutiérrez, María del Pilar Martínez Piñeiro, Luis Cuesta, Angel M. Botella, Luisa Maria |
| author |
Albiñana, Virginia |
| author_facet |
Albiñana, Virginia Gallardo Vara, Eunate de Rojas P, Isabel Recio Poveda, Lucia Aguado, Tania Canto Cano, Ana Aguirre, Daniel T. Serra, Marcelo M. González-Peramato Gutiérrez, María del Pilar Martínez Piñeiro, Luis Cuesta, Angel M. Botella, Luisa Maria |
| author_role |
author |
| author2 |
Gallardo Vara, Eunate de Rojas P, Isabel Recio Poveda, Lucia Aguado, Tania Canto Cano, Ana Aguirre, Daniel T. Serra, Marcelo M. González-Peramato Gutiérrez, María del Pilar Martínez Piñeiro, Luis Cuesta, Angel M. Botella, Luisa Maria |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Departamento de Anatomía Patológica Facultad de Medicina |
| dc.subject.none.fl_str_mv |
anticarcinogenic CcRCC HIF ICI-118,551 propranolol VHL β-adrenergic receptor antagonist Medicina |
| topic |
anticarcinogenic CcRCC HIF ICI-118,551 propranolol VHL β-adrenergic receptor antagonist Medicina |
| description |
Von Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of β2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL−/− ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumors |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020 2020-08-25 |
| dc.type.none.fl_str_mv |
research article http://purl.org/coar/resource_type/c_2df8fbb1 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
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article |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10486/719145 https://dx.doi.org/10.3390/jcm9092740 |
| url |
http://hdl.handle.net/10486/719145 https://dx.doi.org/10.3390/jcm9092740 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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MDPI |
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MDPI |
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Universidad Autónoma de Madrid |
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