ArticleBiomarker research2018
Combination statin and chemotherapy inhibits proliferation and cytotoxicity of an aggressive natural killer cell leukemia.
Article in Biomarker research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Development and In Vitro Evaluation of Atorvastatin and Rutin Co-Loaded Nanoliposomes for Enhanced Anti-Inflammatory and Cytotoxic Efficacy.International journal of molecular sciences · 2026Article
- Unveiling the potential benefits of statins in medulloblastoma treatment: A promising therapeutic approach.IBRO neuroscience reports · 2025Review
- A Novel Ferroptosis-Related Gene Prognosis Signature and Identifying Atorvastatin as a Potential Therapeutic Agent for Hepatocellular Carcinoma.Current issues in molecular biology · 2025Article
- Pharmacokinetic interaction between regorafenib and atorvastatin in rats.Pharmacological reports : PR · 2024Article
- Exploring a repurposed candidate with dual hIDO1/hTDO2 inhibitory potential for anticancer efficacy identified through pharmacophore-based virtual screening and in vitro evaluation.Scientific reports · 2024Article
- Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges.Current obesity reports · 2024Review
- p140Cap modulates the mevalonate pathway decreasing cell migration and enhancing drug sensitivity in breast cancer cells.Cell death & disease · 2023Article
- Review
- mExperimental hematology & oncology · 2022Review
- Fluvastatin sensitizes pancreatic cancer cells toward radiation therapy and suppresses radiation- and/or TGF-β-induced tumor-associated fibrosis.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Statins Lower Lipid Synthesis But Promote Secretion of Cholesterol-Enriched Extracellular Vesicles and Particles.Frontiers in oncology · 2022Article
- Fluvastatin enhances IL-33-mediated mast cell IL-6 and TNF production.Cellular immunology · 2022Article
- Autophagic Activation and Decrease of Plasma Membrane Cholesterol Contribute to Anticancer Activities in Non-Small Cell Lung Cancer.Molecules (Basel, Switzerland) · 2021Article
- Atorvastatin facilitates chemotherapy effects in metastatic triple-negative breast cancer.British journal of cancer · 2021Article
- A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy.Pharmaceutics · 2021Article
- Lovastatin reduces PEL cell survival by phosphorylating ERK1/2 that blocks the autophagic flux and engages a cross-talk with p53 to activate p21.IUBMB life · 2021Article
- Post-Diagnostic Statin Use Reduces Mortality in South Korean Patients with Dyslipidemia and Gastrointestinal Cancer.Journal of clinical medicine · 2021Article
- Statin as a Potential Chemotherapeutic Agent: Current Updates as a Monotherapy, Combination Therapy, and Treatment for Anti-Cancer Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Selective drug combination vulnerabilities in STAT3- and TP53-mutant malignant NK cells.Blood advances · 2021Article
- An Electrochemical Strategy for the Simultaneous Detection of Doxorubicin and Simvastatin for Their Potential Use in the Treatment of Cancer.Biosensors · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAggressive natural killer cell leukemia is a devastating disease, with an average patient survival time of less than 2 months following diagnosis. Due to P-glycoprotein-mediated resistance of the tumor cells most forms of chemotherapy are of limited efficacy, therefore new treatment strategies are needed. Statin drugs have recently been found to inhibit the growth of various tumor cell types.
methodsWe investigated the effects of statin drug-mediated mevalonate pathway inhibition on cell proliferation, tumor-induced cytotoxicity, cell cycle progression and ERK MAP kinase signal transduction pathway activation. Flow cytometry was used to perform the cytotoxicity and cell cycle analyses and Western blotting was used to investigate ERK MAP kinase activation. Statistical significance was assessed by Student's t-test.
resultsFluvastatin and atorvastatin were found to inhibit cell growth and tumor-induced cytotoxicity. These effects were reversed by the addition of mevalonate, signifying that the impact of the drugs were on the mevalonate pathway. Both drugs affected cell cycle progression by causing a significant increase in the percentage of cells in the G0/G1 phase and a reduction in the S phase and the G2/M phases of the cell cycle. Low concentrations of statin drugs were able to abrogate ERK MAP kinase pathway activation, which is typically constitutively activated in aggressive natural killer cell leukemias and important in tumor-mediated cytotoxicity. Addition of statins to chemotherapy caused enhanced inhibition of cell growth and cytotoxicity, compared to either agent alone; a combination therapy that could conceivably benefit some patients.
conclusionsThese investigations suggest that inhibiting the mevalonate pathway might provide a more effective therapy against this deadly disease when combined with chemotherapy. Given that millions of people are currently taking statin drugs to lower cholesterol levels, the risk profile for statin drugs and their side effects are well-known. Our studies suggest that it may be beneficial to explore statin-chemotherapy combination in the treatment of aggressive natural killer cell leukemias.
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