Potential molecular targets of statins in the prevention of hepatocarcinogenesis

Autores
Ridruejo, Ezequiel; Romero Caími, Giselle; Obregón, María J.; Kleiman, Diana Leonor; Alvarez, Laura
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction and aim. Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-β1) and thyroid hormones (TH) regulation. Aim. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model. Materials and methods. We used two models: in vivo (in rats) using di-ethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC. We analyzed cell proliferation parameters (proliferating cell nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, cholesterol metabolism, TGF-β1 mRNA, c-Src and TH levels. Results. In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at maximum doses: AT (30 μM), and SM (20 μM). Increases in PCNA, TGF-β1, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses. Conclusion. Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-β1, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.
Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina
Fil: Romero Caími, Giselle. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Obregón, María J.. Consejo Superior de Investigaciones Científicas; España
Fil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Materia
HEPATOCELLULAR CARCINOMA
HMGCOAR
STATINS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/156492
Acceder
id CONICETDig_5b9ad0f94692af87536563ef6718f5e1
oai_identifier_str oai:ri.conicet.gov.ar:11336/156492
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Potential molecular targets of statins in the prevention of hepatocarcinogenesisRidruejo, EzequielRomero Caími, GiselleObregón, María J.Kleiman, Diana LeonorAlvarez, LauraHEPATOCELLULAR CARCINOMAHMGCOARSTATINShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Introduction and aim. Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-β1) and thyroid hormones (TH) regulation. Aim. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model. Materials and methods. We used two models: in vivo (in rats) using di-ethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC. We analyzed cell proliferation parameters (proliferating cell nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, cholesterol metabolism, TGF-β1 mRNA, c-Src and TH levels. Results. In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at maximum doses: AT (30 μM), and SM (20 μM). Increases in PCNA, TGF-β1, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses. Conclusion. Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-β1, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Romero Caími, Giselle. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Obregón, María J.. Consejo Superior de Investigaciones Científicas; EspañaFil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaMexican Association of Hepatology2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/156492Ridruejo, Ezequiel; Romero Caími, Giselle; Obregón, María J.; Kleiman, Diana Leonor; Alvarez, Laura; Potential molecular targets of statins in the prevention of hepatocarcinogenesis; Mexican Association of Hepatology; Annals of Hepatology; 17; 3; 8-2017; 490-5001665-2681CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1665268119302054info:eu-repo/semantics/altIdentifier/doi/10.5604/01.3001.0011.7394info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:49:32Zoai:ri.conicet.gov.ar:11336/156492instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:49:32.651CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Potential molecular targets of statins in the prevention of hepatocarcinogenesis
title Potential molecular targets of statins in the prevention of hepatocarcinogenesis
spellingShingle Potential molecular targets of statins in the prevention of hepatocarcinogenesis
Ridruejo, Ezequiel
HEPATOCELLULAR CARCINOMA
HMGCOAR
STATINS
title_short Potential molecular targets of statins in the prevention of hepatocarcinogenesis
title_full Potential molecular targets of statins in the prevention of hepatocarcinogenesis
title_fullStr Potential molecular targets of statins in the prevention of hepatocarcinogenesis
title_full_unstemmed Potential molecular targets of statins in the prevention of hepatocarcinogenesis
title_sort Potential molecular targets of statins in the prevention of hepatocarcinogenesis
dc.creator.none.fl_str_mv Ridruejo, Ezequiel
Romero Caími, Giselle
Obregón, María J.
Kleiman, Diana Leonor
Alvarez, Laura
author Ridruejo, Ezequiel
author_facet Ridruejo, Ezequiel
Romero Caími, Giselle
Obregón, María J.
Kleiman, Diana Leonor
Alvarez, Laura
author_role author
author2 Romero Caími, Giselle
Obregón, María J.
Kleiman, Diana Leonor
Alvarez, Laura
author2_role author
author
author
author
dc.subject.none.fl_str_mv HEPATOCELLULAR CARCINOMA
HMGCOAR
STATINS
topic HEPATOCELLULAR CARCINOMA
HMGCOAR
STATINS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction and aim. Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-β1) and thyroid hormones (TH) regulation. Aim. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model. Materials and methods. We used two models: in vivo (in rats) using di-ethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC. We analyzed cell proliferation parameters (proliferating cell nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, cholesterol metabolism, TGF-β1 mRNA, c-Src and TH levels. Results. In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at maximum doses: AT (30 μM), and SM (20 μM). Increases in PCNA, TGF-β1, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses. Conclusion. Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-β1, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.
Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; Argentina
Fil: Romero Caími, Giselle. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Obregón, María J.. Consejo Superior de Investigaciones Científicas; España
Fil: Kleiman, Diana Leonor. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Alvarez, Laura. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
description Introduction and aim. Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins, may reduce the incidence of various tumors, including HCC. Antitumoral activities may be mediated by changes in transforming growth factor-beta (TGF-β1) and thyroid hormones (TH) regulation. Aim. The aim of our study is to establish the statins mechanism of action and the potential key molecules involved in an in vivo and in vitro HCC model. Materials and methods. We used two models: in vivo (in rats) using di-ethylnitrosamine (DEN) and hexachlorobenzene (HCB) to develop HCC. We analyzed cell proliferation parameters (proliferating cell nuclear antigen, PCNA) and cholesterol metabolism (hydroxy-methylglutaryl-CoA reductase, HMGCoAR). In vitro (Hep-G2 cells) we evaluated the effects of different doses of Atorvastatin (AT) and Simvastatin (SM) on HCB induced proliferation and analyzed proliferative parameters, cholesterol metabolism, TGF-β1 mRNA, c-Src and TH levels. Results. In vivo, we observed that cell proliferation significantly increased as well as cholesterol serum levels in rats treated with HCB. In vitro, we observed the same results on PCNA as in vivo. The statins prevented the increase in HMG-CoAR mRNA levels induced by HCB, reaching levels similar to controls at maximum doses: AT (30 μM), and SM (20 μM). Increases in PCNA, TGF-β1, and pc-Src, and decreases in deiodinase I mRNA levels induced by HCB were not observed when cells were pre-treated with AT and SM at maximum doses. Conclusion. Statins can prevent the proliferative HCB effects on Hep-G2 cells. TGF-β1, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.
publishDate 2017
dc.date.none.fl_str_mv 2017-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/156492
Ridruejo, Ezequiel; Romero Caími, Giselle; Obregón, María J.; Kleiman, Diana Leonor; Alvarez, Laura; Potential molecular targets of statins in the prevention of hepatocarcinogenesis; Mexican Association of Hepatology; Annals of Hepatology; 17; 3; 8-2017; 490-500
1665-2681
CONICET Digital
CONICET
url http://hdl.handle.net/11336/156492
identifier_str_mv Ridruejo, Ezequiel; Romero Caími, Giselle; Obregón, María J.; Kleiman, Diana Leonor; Alvarez, Laura; Potential molecular targets of statins in the prevention of hepatocarcinogenesis; Mexican Association of Hepatology; Annals of Hepatology; 17; 3; 8-2017; 490-500
1665-2681
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1665268119302054
info:eu-repo/semantics/altIdentifier/doi/10.5604/01.3001.0011.7394
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Mexican Association of Hepatology
publisher.none.fl_str_mv Mexican Association of Hepatology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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