ArticleLipids in health and disease2017
Isoprenoids responsible for protein prenylation modulate the biological effects of statins on pancreatic cancer cells.
Article in Lipids in health and disease, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- Unveiling the potential benefits of statins in medulloblastoma treatment: A promising therapeutic approach.IBRO neuroscience reports · 2025Review
- Combined Effects of Atorvastatin and Glucose Deprivation on Metabolic Stress and Lipid-Raft Disruption in Glioblastoma and Breast Cancer Cells.Pharmaceutics · 2025Article
- Anti-inflammatory effect of fluvastatin on polarized macrophages and its dependence on the mevalonate pathway.Scientific reports · 2025Article
- Targeting the mevalonate pathway enhances the efficacy of 5-fluorouracil by regulating pyroptosis.Medical oncology (Northwood, London, England) · 2024Article
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- Fatty acids abrogate the growth-suppressive effects induced by inhibition of cholesterol flux in pancreatic cancer cells.Cancer cell international · 2023Article
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- Molecular Research in Pancreatic Cancer: Small Molecule Inhibitors, Their Mechanistic Pathways and Beyond.Current issues in molecular biology · 2023Review
- Inverse Association between Statin Use and Cancer Mortality Relates to Cholesterol Level.Cancers · 2022Article
- Small-Molecule RAS Inhibitors as Anticancer Agents: Discovery, Development, and Mechanistic Studies.International journal of molecular sciences · 2022Review
- Cholesterol-Lowering Phytochemicals: Targeting the Mevalonate Pathway for Anticancer Interventions.Frontiers in genetics · 2022Review
- Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis.Cell reports · 2021Article
- Pitavastatin Is a Highly Potent Inhibitor of T-Cell Proliferation.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Efficacy of fluvastatin and aspirin for prevention of hormonally insensitive breast cancer.Breast cancer research and treatment · 2021Article
- Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies.International journal of molecular sciences · 2021Article
- Natural Products Attenuating Biosynthesis, Processing, and Activity of Ras Oncoproteins: State of the Art and Future Perspectives.Biomolecules · 2020Review
- Cholesterol metabolism drives regulatory B cell IL-10 through provision of geranylgeranyl pyrophosphate.Nature communications · 2020Article
- Lipid rafts as signaling hubs in cancer cell survival/death and invasion: implications in tumor progression and therapy: Thematic Review Series: Biology of Lipid Rafts.Journal of lipid research · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundStatin treatment of hypercholesterolemia is accompanied also with depletion of the mevalonate intermediates, including farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) necessary for proper function of small GTPases. These include Ras proteins, prevalently mutated in pancreatic cancer. In our study, we evaluated the effect of three key intermediates of the mevalonate pathway on GFP-K-Ras protein localization and the gene expression profile in pancreatic cancer cells after exposure to individual statins.
methodsThese effects were tested on MiaPaCa-2 human pancreatic cancer cells carrying a K-Ras activating mutation (G12C) after exposure to individual statins (20 μM). The effect of statins (atorvastatin, lovastatin, simvastatin, fluvastatin, cerivastatin, rosuvastatin, and pitavastatin) and mevalonate intermediates on GFP-K-Ras protein translocation was analyzed using fluorescence microscopy. The changes in gene expression induced in MiaPaCa-2 cells treated with simvastatin, FPP, GGPP, and their combinations with simvastatin were examined by whole genome DNA microarray analysis.
resultsAll tested statins efficiently inhibited K-Ras protein trafficking from cytoplasm to the cell membrane of the MiaPaCa-2 cells. The inhibitory effect of statins on GFP-K-Ras protein trafficking was partially prevented by addition of any of the mevalonate pathway's intermediates tested. Expressions of genes involved in metabolic and signaling pathways modulated by simvastatin treatment was normalized by the concurrent addition of FPP or GGPP. K-Ras protein trafficking within the pancreatic cancer cells is effectively inhibited by the majority of statins; the inhibition is eliminated by isoprenoid intermediates of the mevalonate pathway.
conclusionsOur data indicate that the anticancer effects of statins observed in numerous studies to a large extent are mediated through isoprenoid intermediates of the mevalonate pathway, as they influence expression of genes involved in multiple intracellular pathways.
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