ArticleOncotarget2017
Mevastatin blockade of autolysosome maturation stimulates LBH589-induced cell death in triple-negative breast cancer cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- The Influence of Statin Use on Chemotherapeutic Efficacy in Studies of Mouse Models: A Systematic Review.Anticancer research · 2023Pooled it
- 27-Hydroxycholesterol in cancer development and drug resistance.Journal of enzyme inhibition and medicinal chemistry · 2025Review
- The role of statins in the regulation of breast and colorectal cancer and future directions.Frontiers in pharmacology · 2025Review
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- Apigenin and its combination with Vorinostat induces apoptotic-mediated cell death in TNBC by modulating the epigenetic and apoptotic regulators and related miRNAs.Scientific reports · 2024Article
- Cancer and Cardiovascular Disease: The Conjoined Twins.Cancers · 2024Review
- Review
- Repositioning of HMG-CoA Reductase Inhibitors as Adjuvants in the Modulation of Efflux Pump-Mediated Bacterial and Tumor Resistance.Antibiotics (Basel, Switzerland) · 2023Review
- Post-diagnostic statin use and breast cancer-specific mortality: a population-based cohort study.Breast cancer research and treatment · 2023Article
- Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- Review
- Therapeutic targeting of the mevalonate-geranylgeranyl diphosphate pathway with statins overcomes chemotherapy resistance in small cell lung cancer.Nature cancer · 2022Article
- Pitavastatin Induces Cancer Cell Apoptosis by Blocking Autophagy Flux.Frontiers in pharmacology · 2022Article
- Crosstalk between Statins and Cancer Prevention and Therapy: An Update.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Association of statin use with clinical outcomes in patients with triple-negative breast cancer.Cancer · 2021Article
- Statins: a repurposed drug to fight cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Role of lysosomes in physiological activities, diseases, and therapy.Journal of hematology & oncology · 2021Review
- Valproic Acid Regulates HR and Cell Cycle Through MUS81-pRPA2 Pathway in Response to Hydroxyurea.Frontiers in oncology · 2021Article
- Synergetic Action of Forskolin and Mevastatin Induce Normalization of Lipids Profile in Dyslipidemic Rats through Adenosine Monophosphate Kinase Upregulation.BioMed research international · 2021Article
- Synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting CSCs compartment via YAP inhibition.Journal of experimental & clinical cancer research : CR · 2020Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, and combining a HDACi with other agents is an attractive therapeutic strategy in solid tumors. We report here that mevastatin increases HDACi LBH589-induced cell death in triple-negative breast cancer (TNBC) cells. Combination treatment inhibited autophagic flux by preventing Vps34/Beclin 1 complex formation and downregulating prenylated Rab7, an active form of the small GTPase necessary for autophagosome-lysosome fusion. This means that co-treatment with mevastatin and LBH589 activated LKB1/AMPK signaling and subsequently inhibited mTOR. Co-treatment also led to cell cycle arrest in G2/M phase and induced corresponding expression changes of proteins regulating the cell cycle. Co-treatment also increased apoptosis both in vitro and in vivo, and reduced tumor volumes in xenografted mice. Our results indicate that disruption of autophagosome-lysosome fusion likely underlies mevastatin-LBH589 synergistic anticancer effects. This study confirms the synergistic efficacy of, and demonstrates a potential therapeutic role for mevastatin plus LBH589 in targeting aggressive TNBC, and presents a novel therapeutic strategy for further clinical study. Further screening for novel autophagy modulators could be an efficient approach to enhance HDACi-induced cell death in solid tumors.
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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.