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The effect of simvastatin on lipid droplets accumulation in human embryonic kidney cells and pancreatic cancer cells
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SYSNO ASEP 0425127 Document Type J - Journal Article R&D Document Type The record was not marked in the RIV Subsidiary J Článek ve WOS Title The effect of simvastatin on lipid droplets accumulation in human embryonic kidney cells and pancreatic cancer cells Author(s) Gbelcová, H. (CZ)
Sveda, M. (CZ)
Laubertová, L. (SK)
Varga, I. (SK)
Vítek, L. (CZ)
Kolář, M. (CZ)
Strnad, H. (CZ)
Zelenka, Jaroslav (FGU-C) RID
Boehmer, D. (SK)
Ruml, T. (CZ)Source Title Lipids in Health and Disease
Roč. 12, AUG 21 (2013), s. 126Number of pages 9 s. Language eng - English Country GB - United Kingdom Keywords simvastatin ; lipid droplets ; DNA microarray Subject RIV EB - Genetics ; Molecular Biology Institutional support FGU-C - RVO:67985823 UT WOS 000323719600001 EID SCOPUS 84882440685 DOI 10.1186/1476-511X-12-126 Annotation Background: Statins (HMG-CoA reductase inhibitors) represent a major class of compounds for the treatment of hypercholesterolemia due to their ability to inhibit de novo cholesterol synthesis. In addition to their hypolipidemic effects, chemoprotective properties have been attributed to statins as well. These effects involve multiple mechanisms, which, however, are not known in detail. The aim of our study was to assess in non-malignant as well as cancer cells the impact of simvastatin on the amount of cytosolic lipid droplets (LDs) implicated in many biological processes including proliferation, inflammation, carcinogenesis, apoptosis, necrosis or growth arrest. Methods: Human embryonic kidney cells HEK-293T and human pancreatic cancer cells MiaPaCa-2 were treated with simvastatin (6 and 12 mu M) for 24 and 48 hours respectively. Neutral lipid probe Nile Red was used for detection of LDs by fluorescence microscopy. Cellular cholesterol content was determined by HPLC. Changes in expression of genes related to lipid metabolism in simvastatin-treated MiaPaCa-2 cells were examined by DNA microarray analysis. Validation of gene expression changes was performed using quantitative RT-PCR. Results: The treatment of the cells with simvastatin increased their intracellular content of LDs in both non-malignant as well as cancer cells, partially due to the uptake of cholesterol and triacylglyceroles from medium; but in particular, due to enhanced synthesis of triacylglyceroles as proved by significant overexpression of genes related to de novo synthesis of triacylglyceroles and phospholipids. In addition, simvastatin also markedly influenced expression of genes directly affecting cell proliferation and signaling. Conclusions: Simvastatin treatment led to accumulation of cytosolic LDs within the examined cells, a phenomenon which might contribute to the antiproliferative effects of statins Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2014
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