ArticleScientific reports2017
Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer.
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 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- The Potential of Mushroom Extracts to Improve Chemotherapy Efficacy in Cancer Cells: A Systematic Review.Cells · 2024Pooled it
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- Prenols and prenoic acids in metabolism, disease, and aging.Journal of lipid research · 2026Review
- The emerging role of cholesterol metabolism in gynecologic cancer development and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Galanthamine Fails to Reverse P-gp-Mediated Paclitaxel Resistance in Ovarian Cancer Cell Lines.Biomedicines · 2025Article
- Unbiased combination screening on repurposed drugs reveals synergistic potential of copanlisib and cerivastatin against chemoresistant high-grade serous ovarian cancer.Journal of ovarian research · 2025Article
- Mevalonate Biosynthesis is a Metabolic Vulnerability of Gemcitabine-resistant Pancreatic Cancer.bioRxiv : the preprint server for biology · 2025Article
- Article
- The Mevalonate Pathway in the Radiation Response of Cancer.International journal of radiation oncology, biology, physics · 2025Review
- Host-Derived Geranylgeraniol Shields Intraerythrocytic Stages of Malaria Parasites from Fosmidomycin.Research square · 2025Article
- Navigating Metabolic Challenges in Ovarian Cancer: Insights and Innovations in Drug Repurposing.Cancer medicine · 2025Review
- Exploring Metabolic Approaches for Epithelial Ovarian Cancer Therapy.Journal of cellular physiology · 2025Review
- Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer.Cancer research · 2024Article
- In vivo CRISPR screening identifies geranylgeranyl diphosphate as a pancreatic cancer tumor growth dependency.Molecular metabolism · 2024Article
- Mononuclear phagocyte morphological response to chemoattractants is dependent on geranylgeranyl pyrophosphate.American journal of physiology. Endocrinology and metabolism · 2024Article
- Exploration of bioactive compounds from3 Biotech · 2024Article
- Role of hydroxymethylglutharyl-coenzyme A reductase in the induction of stem-like states in breast cancer.Journal of cancer research and clinical oncology · 2024Article
- Beyond the MEP Pathway: A novel kinase required for prenol utilization by malaria parasites.PLoS pathogens · 2024Article
- Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins.International journal of molecular sciences · 2023Review
- Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors.Cancer research communications · 2023Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pre-clinical and retrospective studies of patients using statins to reduce plasma cholesterol have suggested that statins may be useful to treat cancer. However, prospective clinical trials have yet to demonstrate significant efficacy. We have previously shown that this is in part because a hydrophobic statin with a long half-life is necessary. Pitavastatin, the only statin with this profile, has not undergone clinical evaluation in oncology. The target of pitavastatin, hydroxymethylglutarate coenzyme-A reductase (HMGCR), was found to be over-expressed in all ovarian cancer cell lines examined and upregulated by mutated TP53, a gene commonly altered in ovarian cancer. Pitavastatin-induced apoptosis was blocked by geranylgeraniol and mevalonate, products of the HMGCR pathway, confirming that pitavastatin causes cell death through inhibition of HMGCR. Solvent extracts of human and mouse food were also able to block pitavastatin-induced apoptosis, suggesting diet might influence the outcome of clinical trials. When nude mice were maintained on a diet lacking geranylgeraniol, oral pitavastatin caused regression of Ovcar-4 tumour xenografts. However, when the animal diet was supplemented with geranylgeraniol, pitavastatin failed to prevent tumour growth. This suggests that a diet containing geranylgeraniol can limit the anti-tumour activity of pitavastatin and diet should be controlled in clinical trials of statins.
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