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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3765626 | PMC |
| http://dx.doi.org/10.1186/1476-511X-12-126 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ref-1 is overexpressed in neovascular eye disease and targetable with a novel inhibitor.
Angiogenesis
January 2025
Department of Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA.
Reduction-oxidation factor-1 or apurinic/apyrimidinic endonuclease 1 (Ref-1/APE1) is a crucial redox-sensitive activator of transcription factors such as NF-κB, HIF-1α, STAT-3 and others. It could contribute to key features of ocular neovascularization including inflammation and angiogenesis; these underlie diseases like neovascular age-related macular degeneration (nAMD). We previously revealed a role for Ref-1 in the growth of ocular endothelial cells and in choroidal neovascularization (CNV).
View Article and Find Full Text PDFCharacterization of stem cell landscape and identification of stemness-relevant prognostic gene signature to aid immunotherapy in breast cancer.
Discov Oncol
January 2025
Department of General Surgery, The Second Affiliated Hospital of the Air Force Medical University, Xi'an, 710038, China.
A common digestive system cancer with a dismal prognosis and a high death rate globally is breast cancer (BRCA). BRCA recurrence, metastasis, and medication resistance are all significantly impacted by cancer stem cells (CSCs). However, the relationship between CSCs and the tumor microenvironment in BRCA individuals remains unknown, and this information is critically needed.
View Article and Find Full Text PDFHydrogen Sulfide Promotes TAM-M1 Polarization through Activating IRE-1α Pathway via GRP78 S-Sulfhydrylation to against Breast Cancer.
Adv Sci (Weinh)
January 2025
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, China.
Hydrogen sulfide (HS)-mediated protein S-sulfhydration has been shown to play critical roles in several diseases. Tumor-associated macrophages (TAMs) are the predominant population of immune cells present within solid tumor tissues, and they function to restrict antitumor immunity. However, no previous study has investigated the role of protein S-sulfhydration in TAM reprogramming in breast cancer (BC).
View Article and Find Full Text PDFBerberine restrains non-small cell lung cancer cell growth, invasion and glycolysis via inactivating the SPC25/NUF2 pathway.
Naunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Respiratory and Critical Care Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, No. 111, Dade Road, Guangzhou, 510120, China.
Berberine (BBR) has been proved to inhibit the malignant progression of non-small cell lung cancer (NSCLC), but the underlying molecular mechanism still needs to be further revealed. NSCLC cells (A549 and H1299) were treated with BBR. CCK8 assay, colony formation assay, flow cytometry, TUNEL staining and transwell assay were used to examine cell proliferation, apoptosis and invasion.
View Article and Find Full Text PDFPrognostic implications and therapeutic opportunities related to CAF subtypes in CMS4 colorectal cancer: insights from single-cell and bulk transcriptomics.
Apoptosis
January 2025
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Cancer-associated fibroblasts (CAFs) significantly influence tumor progression and therapeutic resistance in colorectal cancer (CRC). However, the distributions and functions of CAF subpopulations vary across the four consensus molecular subtypes (CMSs) of CRC. This study performed single-cell RNA and bulk RNA sequencing and revealed that myofibroblast-like CAFs (myCAFs), tumor-like CAFs (tCAFs), inflammatory CAFs (iCAFs), CXCL14CAFs, and MTCAFs are notably enriched in CMS4 compared with other CMSs of CRC.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!