ArticleLaboratory investigation; a journal of technical methods and pathology2019
Anti-cancer effect of doxorubicin is mediated by downregulation of HMG-Co A reductase via inhibition of EGFR/Src pathway.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 55 citations in OpenAlex.
- Combination of Simvastatin and FAC Improves Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.Cancer research and treatment · 2021Trial
- Synthesis of Pyrido[2,3-d]Azolopyrimidinones: Design and Epidermal Growth Factor Receptor-Targeted Molecular Docking Toward Novel Anticancer Leads.ChemistryOpen · 2026Article
- Targeting cancer stem-like cells via cholesterol modulation and ferroptosis induction using a multifunctional nanoplatform to overcome drug resistance.Journal of nanobiotechnology · 2025Article
- Cobalt-nickel metal-organic frameworks (CNMs) as drug delivery agents for triple-negative breast cancer.Nanoscale advances · 2025Article
- Accumulation Kinetics and Biological Action of Doxorubicin in Rabbit Intervertebral Discs.International journal of molecular sciences · 2025Article
- Machine Learning-Based Prognostic Signature in Breast Cancer: Regulatory T Cells, Stemness, and Deep Learning for Synergistic Drug Discovery.International journal of molecular sciences · 2025Article
- Amniotic membrane promotes doxorubicin potency by suppressing SH-SY5Y neuroblastoma cell angiogenesis.BMC cancer · 2025Article
- Doxorubicin-mediated testicular toxicity is associated with dysregulated mTOR/Beclin-1 pathways, oxidative stress, inflammation and apoptosis in Wistar rats: preventive role of lutein.Laboratory animal research · 2025Article
- Application of MMP-2-responsiveRSC advances · 2025Article
- Article
- Pituitary tumor‑transforming gene 1 regulates the senescence and apoptosis of oral squamous cell carcinoma in a p21‑dependent DNA damage response manner.Oncology reports · 2024Article
- MiRNA-449 family is epigenetically repressed and sensitizes to doxorubicin through ACSL4 downregulation in triple-negative breast cancer.Cell death discovery · 2024Article
- Erianin inhibits the progression of triple-negative breast cancer by suppressing SRC-mediated cholesterol metabolism.Cancer cell international · 2024Article
- Doxorubicin as a Potential Treatment Option in Canine Mammary Tumors.Veterinary sciences · 2023Article
- Rafting on the Evidence for Lipid Raft-like Domains as Hubs Triggering Environmental Toxicants' Cellular Effects.Molecules (Basel, Switzerland) · 2023Review
- Racial Disparity in Anthracycline-induced Cardiotoxicity in Breast Cancer Patients.Biomedicines · 2023Review
- Biological Activities of Bismuth Compounds: An Overview of the New Findings and the Old Challenges Not Yet Overcome.Molecules (Basel, Switzerland) · 2023Review
- Perturbing plasma membrane lipid: a new paradigm for tumor nanotherapeutics.Theranostics · 2023Review
- Fish Oil and Selenium with Doxorubicin Modulates Expression of Fatty Acid Receptors and Selenoproteins, and Targets Multiple Anti-Cancer Signaling in Triple-negative Breast Cancer Tumors.International journal of medical sciences · 2022Article
- Multi-Functional Liposome: A Powerful Theranostic Nano-Platform Enhancing Photodynamic Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin is a widely used DNA damage-inducing anti-cancer drug. However, its use is limited by its dose-dependent side effects, such as cardiac toxicity. Cholesterol-lowering statin drugs increase the efficacy of some anti-cancer drugs. Cholesterol is important for cell growth and a critical component of lipid rafts, which are plasma membrane microdomains important for cell signaling. 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMG-CR) is a critical enzyme in cholesterol synthesis. Here, we show that doxorubicin downregulated HMG-CR protein levels and thus reduced levels of cholesterol and lipid rafts. Cholesterol addition attenuated doxorubicin-induced cell death, and cholesterol depletion enhanced it. Reduction of HMG-CR activity by simvastatin, a statin that acts as an HMG-CR inhibitor, or by siRNA-mediated HMG-CR knockdown enhanced doxorubicin cytotoxicity. Doxorubicin-induced HMG-CR downregulation was associated with inactivation of the EGFR-Src pathway. Furthermore, a high-cholesterol-diet attenuated the anti-cancer activity of doxorubicin in a tumor xenograft mouse model. In a multivulva model of Caenorhabditis elegans expressing an active-EGFR mutant, doxorubicin decreased hyperplasia more efficiently in the absence than in the presence of cholesterol. These data indicate that EGFR/Src/HMG-CR is a new pathway mediating doxorubicin-induced cell death and that cholesterol control could be combined with doxorubicin treatment to enhance efficacy and thus reduce side effects.
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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.