The effect of simvastatin on lipid droplets accumulation in human embryonic kidney cells and pancreatic cancer cells.

Abstract

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 μM) 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.

• Authors: Helena Gbelcová, Martin Svéda, Lucia Laubertová, Ivan Varga, Libor Vítek, Michal Kolář, Hynek Strnad, Jaroslav Zelenka, Daniel Böhmer, Tomáš Ruml
• Journal: Lipids in health and disease (Lipids Health Dis) Vol. 12 Pg. 126 (Aug 21 2013) ISSN: 1476-511X [Electronic] England
• PMID: 23961716 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Cholesterol
• Simvastatin

Topics

• Cell Line, Tumor (drug effects)
• Cell Proliferation (drug effects, genetics)
• Cholesterol (metabolism)
• Gene Expression Regulation (drug effects)
• HEK293 Cells (drug effects)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Lipid Droplets (drug effects, metabolism)
• Lipid Metabolism (drug effects, genetics)
• Pancreatic Neoplasms (drug therapy, metabolism)
• Simvastatin (pharmacology)