ArticleOncotarget2016
Simvastatin induces heme oxygenase-1 via NF-E2-related factor 2 (Nrf2) activation through ERK and PI3K/Akt pathway in colon cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Association between Statins Types with Incidence of Liver Cancer: An Updated Meta-analysis.Current medicinal chemistry · 2024Pooled it
- The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review.PloS one · 2017Pooled it
- Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson's Disease: Rationale for Clinical Trial, and Current Progress.Journal of Parkinson's disease · 2017Trial
- Statin-Mediated Modulation of Nrf2 Signaling: Mechanisms and Therapeutic Implications in Atherosclerosis.Reviews in cardiovascular medicine · 2026Review
- An Overview of the Antioxidant, Anti-inflammatory, and Anticancer Effects of Statins.Anti-cancer agents in medicinal chemistry · 2026Review
- Article
- Innovations in Drug Discovery for Sickle Cell Disease Targeting Oxidative Stress and NRF2 Activation-A Short Review.International journal of molecular sciences · 2025Review
- Heme oxygenase-1 modulates CD62E-dependent endothelial cell-monocyte interactions and mitigates HLA-I-induced transplant vasculopathy in mice.Frontiers in immunology · 2025Article
- Fluvastatin suppresses hemin-induced cell death, reactive oxygen species generation, and elevated labile iron pool.Hematology, transfusion and cell therapy · 2024Article
- Advances in the Effects of Heat Stress on Ovarian Granulosa Cells: Unveiling Novel Ferroptosis Pathways.Veterinary sciences · 2024Review
- Mechanism of Action and Therapeutic Implications of Nrf2/HO-1 in Inflammatory Bowel Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Pharmacotherapeutic Considerations on Telomere Biology: The Positive Effect of Pharmacologically Active Substances on Telomere Length.International journal of molecular sciences · 2024Review
- Expression of human dCTP pyrophosphatase 1 (DCTPP1) and its association with cisplatin resistance characteristics in ovarian cancer.Journal of cellular and molecular medicine · 2024Article
- Simvastatin-Mediated Nrf2 Activation Induces Fetal Hemoglobin and Antioxidant Enzyme Expression to Ameliorate the Phenotype of Sickle Cell Disease.Antioxidants (Basel, Switzerland) · 2024Article
- Review
- Administration of growth hormone ameliorates adverse effects of total sleep deprivation.Metabolic brain disease · 2023Article
- Network pharmacology-based analysis of heat clearing and detoxifying drug JC724 on the treatment of colorectal cancer.World journal of gastrointestinal oncology · 2023Article
- The different facets of heme-oxygenase 1 in innate and adaptive immunity.Cell biochemistry and biophysics · 2022Review
- Heme Oxygenase-1 as Therapeutic Target for Diabetic Foot Ulcers.International journal of molecular sciences · 2022Review
- Recent Advances on Bioactive Ingredients of Morchella esculenta.Applied biochemistry and biotechnology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Statin has been known not only as their cholesterol-lowering action but also on their pleiotropic effects including anti-inflammatory and anti-oxidant as well as anti-cancer effect. Nrf2 (NF-E2-related factor 2) is a transcription factor to activate cellular antioxidant response to oxidative stress. There are little known whether statins affect activation of Nrf2 and Nrf2 signaling pathway in colon cancer cells. We investigated whether simvastatin stimulates the expression of Nrf2 and nuclear translocation of Nrf2 and which signal pathway is involved in the expression of Nrf2 and antioxidant enzymes. We investigated the effect of simvastatin on the expression of Nrf2 and nuclear translocation of Nrf2 in two human colon cancer cell lines, HT-29 and HCT 116 through cell proliferation assay, Western blotting and immunocytochemical analysis. We evaluated which signal pathway such as ERK or PI3K pathway affect Nrf2 activation and whether simvastatin induces antioxidant enzymes (heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1), γ-glutamate-cysteine ligase catalytic subunit (GCLC)). We demonstrated simvastatin-induced dose-dependent up-regulation of Nrf2 expression and stimulated Nrf2 nuclear translocation in colon cancer cells. We also demonstrated that simvastatin-induced anti-oxidant enzymes (HO-1, NQO1, and GCLC) in HT-29 and HCT 116 cells. PI3K/Akt inhibitor (LY294002) and ERK inhibitor (PD98059) suppressed simvastatin-induced Nrf2 and HO-1 expression in both HT-29 and HCT 116 cells. This study shows that simvastatin induces the activation and nuclear translocation of Nrf2 and the expression of various anti-oxidant enzymes via ERK and PI3K/Akt pathway in colon cancer cells.
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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.