Potential molecular targets of statins in the prevention of hepatocarcinogenesis
Introduction and alm. 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-βΙ) and thyroid hormones (TH) regulation. Aim. The aim of...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268119302054 |
| _version_ | 1819107557320425472 |
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| author | Ezequiel Ridruejo Giselle Romero-Caími María J. Obregón Diana Kleiman de Pisarev Laura Alvarez |
| author_facet | Ezequiel Ridruejo Giselle Romero-Caími María J. Obregón Diana Kleiman de Pisarev Laura Alvarez |
| author_sort | Ezequiel Ridruejo |
| collection | DOAJ |
| description | Introduction and alm. 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-βΙ) 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 diethylnitrosamine (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-βΙ 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-βΙ, 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-βΙ, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis. |
| first_indexed | 2024-12-22T02:55:56Z |
| format | Article |
| id | doaj.art-e32ab4b5e9ee45d29af33dd066d25b85 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-12-22T02:55:56Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-e32ab4b5e9ee45d29af33dd066d25b852022-12-21T18:41:16ZengElsevierAnnals of Hepatology1665-26812018-05-01173490500Potential molecular targets of statins in the prevention of hepatocarcinogenesisEzequiel Ridruejo0Giselle Romero-Caími1María J. Obregón2Diana Kleiman de Pisarev3Laura Alvarez4Hepatology Section, Department of Medicine. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC). Ciudad Autónoma de Buenos Aires, Argentina; Corresponding author.Laboratory of Biological Effects of Environmental Pollutants, Department of Human Biochemistry, School of Medicine. Universidad de Buenos Aires. Ciudad Autónoma de Buenos Aires, ArgentinaDepartment of Molecular Pathophysiology, Instituto de Investigaciones Biomédicas (Centro mixto CSIC-UAM). Madrid, SpainLaboratory of Biological Effects of Environmental Pollutants, Department of Human Biochemistry, School of Medicine. Universidad de Buenos Aires. Ciudad Autónoma de Buenos Aires, ArgentinaLaboratory of Biological Effects of Environmental Pollutants, Department of Human Biochemistry, School of Medicine. Universidad de Buenos Aires. Ciudad Autónoma de Buenos Aires, ArgentinaIntroduction and alm. 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-βΙ) 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 diethylnitrosamine (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-βΙ 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-βΙ, 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-βΙ, c-Src and TH may be the statins molecular targets in hepatocarcinogenesis.http://www.sciencedirect.com/science/article/pii/S1665268119302054Hepatocellular carcinomaTGF-βΙHMGCoARStatins |
| spellingShingle | Ezequiel Ridruejo Giselle Romero-Caími María J. Obregón Diana Kleiman de Pisarev Laura Alvarez Potential molecular targets of statins in the prevention of hepatocarcinogenesis Annals of Hepatology Hepatocellular carcinoma TGF-βΙ HMGCoAR Statins |
| title | 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_short | Potential molecular targets of statins in the prevention of hepatocarcinogenesis |
| title_sort | potential molecular targets of statins in the prevention of hepatocarcinogenesis |
| topic | Hepatocellular carcinoma TGF-βΙ HMGCoAR Statins |
| url | http://www.sciencedirect.com/science/article/pii/S1665268119302054 |
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