ArticleOncotarget2016
Simvastatin-induced breast cancer cell death and deactivation of PI3K/Akt and MAPK/ERK signalling are reversed by metabolic products of the mevalonate pathway.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Efficacy and safety profile of statins in patients with cancer: a systematic review of randomised controlled trials.European journal of clinical pharmacology · 2020Pooled it
- AMPK-Mediated Lipid Metabolic Reprogramming in Cancer: From Mechanisms to Targeted Therapies.Cell biochemistry and function · 2026Review
- Cholesterol as a metabolic integrator of oncogenic signaling, immune evasion, and therapy resistance.Apoptosis : an international journal on programmed cell death · 2026Review
- Atorvastatin promotes lipid catabolism in colorectal cancer via FDFT1‒mediated inhibition of the PI3K/AKT pathway.Cell communication and signaling : CCS · 2026Article
- Statins in Breast Cancer Therapy: Mechanistic Insights and Emerging Evidence.Cancer innovation · 2026Review
- Combining Statins with Radiotherapy for Prostate Cancer: From Photon Experience to Proton Potential.Journal of clinical medicine · 2026Review
- In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Atorvastatin: A Focus on Cervical and Head and Neck Cancers.Pharmaceutics · 2025Article
- Repurposing a Lipid-Lowering Agent to Inhibit TNBC Growth Through Cell Cycle Arrest.Current issues in molecular biology · 2025Article
- Effect of Jiawei Huangqi Guizhi decoction on the expression of gastrin content and phosphatidylinositol 3-kinase/ protein kinase B/mechanistic target of rapamycin complex 2 signalling pathways in rats with chronic atrophic gastritis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Article
- Statin use and liver-related prognosis among patients with MASLD.JHEP reports : innovation in hepatology · 2025Article
- Sodium oleate functionalized simvastatin liposomes: boosting endosomal escape and anticancer efficacy in triple negative breast cancer.Research in pharmaceutical sciences · 2025Article
- Simvastatin inhibits PD-L1 via ILF3 to induce ferroptosis in gastric cancer cells.Cell death & disease · 2025Article
- Genetic association of lipids and lipid-lowering drug target genes with breast cancer.Discover oncology · 2025Article
- Statins as Secondary Preventive Agent to Limit Breast Cancer Metastatic Outgrowth.International journal of molecular sciences · 2025Review
- Statins regulate kinase signaling by causing changes in phosphorylation, rather than through changes in gene expression or direct inhibition: evidence in colorectal cancer.Frontiers in pharmacology · 2025Article
- Mevalonate Metabolic Reprogramming Drives Cisplatin Resistance in Bladder Cancer: Mechanisms and Therapeutic Targeting.Protein and peptide letters · 2025Article
- Targeting the PI3K Pathway: Advancements and Achievements in Breast Cancer Therapy.Current pharmaceutical design · 2025Review
- PI3K Signaling at the Crossroads of Lipid Metabolism and Cancer.Advances in experimental medicine and biology · 2025Review
- Mendelian randomization study on simvastatin and gastric cancer: exploring the therapeutic potential of statins in oncology.Translational cancer research · 2024Article
- The Effect of Statins on Markers of Breast Cancer Proliferation and Apoptosis in Women with In Situ or Early-Stage Invasive Breast Cancer.International journal of molecular sciences · 2024Article
10 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
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Statins purportedly exert anti-tumoral effects on breast cancer. However, the biologic mechanisms for these actions are not fully elucidated. The aims of this study were 1) to explore the effects of simvastatin on apoptosis, proliferation as well as PI3K/Akt/mTOR and MAPK/ERK pathway in a window-of-opportunity breast cancer trial; 2) to further confirm findings from the clinical trial by functional studies; 3) to explore the regulatory role of mevalonate pathway on the anti-tumoral effects of simvastatin. In clinical samples, simvastatin led to increase in cleaved caspase-3 (p = 0.002) and decreased trend for Ki67 (p = 0.245). Simvastatin markedly suppressed PI3K/Akt/mTOR signalling by activating PTEN (p = 0.005) and by dephosphorylating Akt (p = 0.002) and S6RP (p = 0.033); it also inhibited MAPK/ERK pathway by dephosphorylating c-Raf (p = 0.018) and ERK1/2 (p = 0.002). In ER-positive (MCF-7, T47D) and ER-negative (MDA-MB-231, BT-549) breast cancer cells, simvastatin treatment consistently induced apoptosis and inhibited proliferation by deregulating caspase cascades and cell cycle proteins in a dose dependent manner. Concordantly, simvastatin strongly suppressed PI3K/Akt/mTOR pathway by enhancing PTEN expression and by further sequentially dephosphorylating downstream cascades including Akt, mTOR, p70S6K, S6RP and 4E-BP1. Furthermore, simvastatin significantly inhibited MAPK/ERK pathway by dephosphorylating sequential cascades such as c-Raf, MEK1/2 and ERK1/2. These simvastatin anti-tumoral effects were reversed by metabolic products of the mevalonate pathway, including mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate. These findings shed light on the biological and potential anti-tumoral effects of simvastatin in breast cancer.
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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.