ArticleScientific reports2017
Mevalonate Cascade Inhibition by Simvastatin Induces the Intrinsic Apoptosis Pathway via Depletion of Isoprenoids in Tumor Cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Pooled it
- Trial
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- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
- Article
- Statins in Breast Cancer Therapy: Mechanistic Insights and Emerging Evidence.Cancer innovation · 2026Review
- Pharmacologic Modulation of the PAR-2-ERK Axis by Statins Converts Inflammatory Survival Signalling into Apoptosis in Colorectal Cancer Cells.International journal of molecular sciences · 2026Article
- The Expendables: Overlooked Medications with Anti-Cancer Properties.Current oncology reports · 2025Review
- Drug repurposing in oncology: a path beyond the bottleneck.Medical oncology (Northwood, London, England) · 2025Review
- Repurposing a Lipid-Lowering Agent to Inhibit TNBC Growth Through Cell Cycle Arrest.Current issues in molecular biology · 2025Article
- Simvastatin-Mediated Molecular Mechanisms Underlying the Growth Inhibition of Testicular Leydig Tumour Cells.Journal of cellular and molecular medicine · 2025Article
- Unravelling molecular dynamics in living cells: Fluorescent protein biosensors for cell biology.Journal of microscopy · 2025Review
- Sodium oleate functionalized simvastatin liposomes: boosting endosomal escape and anticancer efficacy in triple negative breast cancer.Research in pharmaceutical sciences · 2025Article
- Immune-mediated renal injury in diabetic kidney disease: from mechanisms to therapy.Frontiers in immunology · 2025Review
- A Lipidomics Approach to Determine the Role of Lipids and Its Crosstalk with Autophagy in Lung Cancer Metastasis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Evaluation of Autophagy in Conjunctival Fibroblasts.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Targeting the PI3K Pathway: Advancements and Achievements in Breast Cancer Therapy.Current pharmaceutical design · 2025Review
- Therapeutic Potential of Simvastatin: Cellular Mechanism, Binding Energetics, and Resistance Developments.Current topics in medicinal chemistry · 2025Review
- Potential Synergistic Effect between Niraparib and Statins in Ovarian Cancer Clinical Trials.Cancer research communications · 2025Article
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 5 institutions in 4 countries.
Funding
Abstract
The mevalonate (MEV) cascade is responsible for cholesterol biosynthesis and the formation of the intermediate metabolites geranylgeranylpyrophosphate (GGPP) and farnesylpyrophosphate (FPP) used in the prenylation of proteins. Here we show that the MEV cascade inhibitor simvastatin induced significant cell death in a wide range of human tumor cell lines, including glioblastoma, astrocytoma, neuroblastoma, lung adenocarcinoma, and breast cancer. Simvastatin induced apoptotic cell death via the intrinsic apoptotic pathway. In all cancer cell types tested, simvastatin-induced cell death was not rescued by cholesterol, but was dependent on GGPP- and FPP-depletion. We confirmed that simvastatin caused the translocation of the small Rho GTPases RhoA, Cdc42, and Rac1/2/3 from cell membranes to the cytosol in U251 (glioblastoma), A549 (lung adenocarcinoma) and MDA-MB-231(breast cancer). Simvastatin-induced Rho-GTP loading significantly increased in U251 cells which were reversed with MEV, FPP, GGPP. In contrast, simvastatin did not change Rho-GTP loading in A549 and MDA-MB-231. Inhibition of geranylgeranyltransferase I by GGTi-298, but not farnesyltransferase by FTi-277, induced significant cell death in U251, A549, and MDA-MB-231. These results indicate that MEV cascade inhibition by simvastatin induced the intrinsic apoptosis pathway via inhibition of Rho family prenylation and depletion of GGPP, in a variety of different human cancer cell lines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.