ArticleLeukemia2001
Blocking protein geranylgeranylation is essential for lovastatin-induced apoptosis of human acute myeloid leukemia cells.
Article in Leukemia, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 3 of them syntheses that pooled it.
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Who cites it
91 citing papers in PubMed, 3 syntheses or guidelines pooled it, 211 citations in OpenAlex.
- Statins use and the risk of all and subtype hematological malignancies: a meta-analysis of observational studies.Cancer medicine · 2015Pooled it
- Statin use is associated with reduced risk of haematological malignancies: evidence from a meta-analysis.PloS one · 2014Pooled it
- Use of statins and risk of haematological malignancies: a meta-analysis of six randomized clinical trials and eight observational studies.British journal of clinical pharmacology · 2007Pooled it
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- RNA terminal uridylyl transferases are druggable vulnerabilities in AML but are dispensable for normal hematopoiesis.Science advances · 2026Article
- Statin Use and Genetically Predicted HMG-CoA Reductase Inhibition in Relation to Clonal Hematopoiesis.medRxiv : the preprint server for health sciences · 2026Article
- Cholesterol Reprogramming in Acute Myeloid Leukemia: Integrating Tumor-Intrinsic Metabolism and Immune Crosstalk.Diseases (Basel, Switzerland) · 2026Review
- Prime time for the use of statins in MPNs: from comorbidity drugs to disease-modifying partners.Blood advances · 2026Review
- Statins targeting mevalonate-geranylgeranyl diphosphate pathway inhibit proliferation in NK/T lymphoma by promoting pyroptosis.Translational oncology · 2026Article
- The Contribution of Cholesterol and Squalene Synthase in Cancer: Molecular Mechanisms, Lipid Rafts and Therapeutic Approaches.Medicinal research reviews · 2026Review
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- Structural and Functional Analysis of GGPPS Inhibition as a Therapeutic Mechanism for Acute Myeloid Leukemia (AML).Research square · 2025Article
- Statins induce monocytic differentiation in acute myeloid leukemia cells through the KLF4/DPYSL2A axis.FEBS open bio · 2025Article
- Pitavastatin counteracts venetoclax resistance mechanisms in acute myeloid leukemia by depleting geranylgeranyl pyrophosphate.bioRxiv : the preprint server for biology · 2025Article
- Article
- Impact of fixed phosphorus position on activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2025Article
- Understanding and Targeting Metabolic Vulnerabilities in Acute Myeloid Leukemia: An Updated Comprehensive Review.Cancers · 2025Review
- Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors.Cancer research communications · 2023Article
- Statin Use, Cholesterol Level, and Mortality Among Females With Breast Cancer.JAMA network open · 2023Article
31 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
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lovastatin is an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the major regulatory enzyme of the mevalonate pathway. We have previously reported that lovastatin induces a significant apoptotic response in human acute myeloid leukemia (AML) cells. To identify the critical biochemical mechanism(s) essential for lovastatin-induced apoptosis, add-back experiments were conducted to determine which downstream product(s) of the mevalonate pathway could suppress this apoptotic response. Apoptosis induced by lovastatin was abrogated by mevalonate (MVA) and geranylgeranyl pyrophosphate (GGPP), and was partially inhibited by farnesyl pyrophosphate (FPP). Other products of the mevalonate pathway including cholesterol, squalene, lanosterol, desmosterol, dolichol, dolichol phosphate, ubiquinone, and isopentenyladenine did not affect lovastatin-induced apoptosis in AML cells. Our results suggest that inhibiting geranylgeranylation of target proteins is the predominant mechanism of lovastatin-induced apoptosis in AML cells. In support of this hypothesis, the geranylgeranyl transferase inhibitor (GGTI-298) mimicked the effect of lovastatin, whereas the farnesyl transferase inhibitor (FTI-277) was much less effective at triggering apoptosis in AML cells. Inhibition of geranylgeranylation was monitored and associated with the apoptotic response induced by lovastatin and GGTI-298 in the AML cells. We conclude that blockage of the mevalonate pathway, particularly inhibition of protein geranylgeranylation holds a critical role in the mechanism of lovastatin-induced apoptosis in AML cells.
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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.