{"title":"Some pleiotropic effects of statins on hepatocellular carcinoma cells: Comparative study on atorvastatin, rosuvastatin and simvastatin","authors":"Esmeralda Dautović , Monika Rustemović-Čorbić , Nahida Srabović , Adaleta Softić , Aida Smajlović , Maida Šljivić Husejnović , Alen Hatkić , Dalila Halilčević","doi":"10.1016/j.advms.2023.07.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p><span>For many years, statins have been the most commonly used </span>drugs<span><span> in cholesterol-lowering therapy. In addition to these therapeutic effects, statins exhibit other, pleiotropic effects<span> that can be beneficial, but also harmful to cells and tissues. The aim of this research was to determine and compare the pleiotropic effects of structurally different statins: atorvastatin, simvastatin and </span></span>rosuvastatin<span> at different concentrations on hepatocellular carcinoma (HepG2) cells.</span></span></p></div><div><h3>Materials and methods</h3><p><span><span>The MTT assay was used to determine the cytotoxic effects of statins. The influence of statins on the production of </span>reactive oxygen species (ROS) was determined by measuring fluorescent response of 2,7-dichlorofluorescein </span>diacetate<span> (DCFH-DA). The effect of statins on glucose production and excretion was determined with glucose production assay.</span></p></div><div><h3>Results</h3><p>The obtained results confirmed that all tested statins exhibit cytotoxic effects, increase the production of ROS as well as the production and excretion of glucose from HepG2 cells. It was observed that all the mentioned effects are more pronounced with lipophilic statins, atorvastatin and simvastatin compared to hydrophilic rosuvastatin.</p></div><div><h3>Conclusion</h3><p>The less pronounced pleiotropic effects of rosuvastatin on HepG2 cells are probably due to differences in structure and solubility compared to atorvastatin and simvastatin. Transporter-dependent and a slower influx of rosuvastatin into cells compared to the tested lipophilic statins probably lead to a weaker accumulation of rosuvastatin in HepG2 cells, which results in less pronounced pleiotropic effects compared to lipophilic atorvastatin and simvastatin.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"68 2","pages":"Pages 258-264"},"PeriodicalIF":2.5000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in medical sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1896112623000238","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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Abstract
Purpose
For many years, statins have been the most commonly used drugs in cholesterol-lowering therapy. In addition to these therapeutic effects, statins exhibit other, pleiotropic effects that can be beneficial, but also harmful to cells and tissues. The aim of this research was to determine and compare the pleiotropic effects of structurally different statins: atorvastatin, simvastatin and rosuvastatin at different concentrations on hepatocellular carcinoma (HepG2) cells.
Materials and methods
The MTT assay was used to determine the cytotoxic effects of statins. The influence of statins on the production of reactive oxygen species (ROS) was determined by measuring fluorescent response of 2,7-dichlorofluorescein diacetate (DCFH-DA). The effect of statins on glucose production and excretion was determined with glucose production assay.
Results
The obtained results confirmed that all tested statins exhibit cytotoxic effects, increase the production of ROS as well as the production and excretion of glucose from HepG2 cells. It was observed that all the mentioned effects are more pronounced with lipophilic statins, atorvastatin and simvastatin compared to hydrophilic rosuvastatin.
Conclusion
The less pronounced pleiotropic effects of rosuvastatin on HepG2 cells are probably due to differences in structure and solubility compared to atorvastatin and simvastatin. Transporter-dependent and a slower influx of rosuvastatin into cells compared to the tested lipophilic statins probably lead to a weaker accumulation of rosuvastatin in HepG2 cells, which results in less pronounced pleiotropic effects compared to lipophilic atorvastatin and simvastatin.
期刊介绍：
Advances in Medical Sciences is an international, peer-reviewed journal that welcomes original research articles and reviews on current advances in life sciences, preclinical and clinical medicine, and related disciplines.
The Journal’s primary aim is to make every effort to contribute to progress in medical sciences. The strive is to bridge laboratory and clinical settings with cutting edge research findings and new developments.
Advances in Medical Sciences publishes articles which bring novel insights into diagnostic and molecular imaging, offering essential prior knowledge for diagnosis and treatment indispensable in all areas of medical sciences. It also publishes articles on pathological sciences giving foundation knowledge on the overall study of human diseases. Through its publications Advances in Medical Sciences also stresses the importance of pharmaceutical sciences as a rapidly and ever expanding area of research on drug design, development, action and evaluation contributing significantly to a variety of scientific disciplines.
The journal welcomes submissions from the following disciplines:
General and internal medicine,
Cancer research,
Genetics,
Endocrinology,
Gastroenterology,
Cardiology and Cardiovascular Medicine,
Immunology and Allergy,
Pathology and Forensic Medicine,
Cell and molecular Biology,
Haematology,
Biochemistry,
Clinical and Experimental Pathology.
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