ArticleDrug design, development and therapy2020
Miconazole Contributes to NRF2 Activation by Noncanonical P62-KEAP1 Pathway in Bladder Cancer Cells.
Article in Drug design, development and therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Coenzyme Q10 exerts anti-cancer effects in bladder cancer by inducing ROS-mediated apoptosis and autophagy.Journal of bioenergetics and biomembranes · 2026Article
- Anti-Melanoma Effects of Miconazole: Investigating the Mitochondria Involvement.International journal of molecular sciences · 2024Article
- Sulforaphane's Multifaceted Potential: From Neuroprotection to Anticancer Action.Molecules (Basel, Switzerland) · 2023Review
- ERBB2-PTGS2 axis promotes intervertebral disc degeneration by regulating senescence of nucleus pulposus cells.BMC musculoskeletal disorders · 2023Article
- Anti-oxidative-initiated cognitive impairment amelioration in Alzheimer's disease model rats through preventive transcutaneous electrical acupoint stimulation.Integrative medicine research · 2023Article
- Inaugurating a novel adjuvant therapy in urological cancers: Ferroptosis.Cancer pathogenesis and therapy · 2023Review
- Recent progress in the effect of ferroptosis of HSCs on the development of liver fibrosis.Frontiers in molecular biosciences · 2023Review
- Role of Nrf2, STAT3, and Src as Molecular Targets for Cancer Chemoprevention.Pharmaceutics · 2022Review
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- Effects of Flutriafol Fungicide on the Lipid Accumulation in Human Liver Cells and Rat Liver.Foods (Basel, Switzerland) · 2021Article
- Sulforaphane Impact on Reactive Oxygen Species (ROS) in Bladder Carcinoma.International journal of molecular sciences · 2021Review
- Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species-mediated endoplasmic reticulum stress.Oncology letters · 2021Article
- Therapeutic Targeting of the NRF2 Signaling Pathway in Cancer.Molecules (Basel, Switzerland) · 2021Review
- P62/SQSTM1/Keap1/NRF2 Axis Reduces Cancer Cells Death-Sensitivity in Response to Zn(II)-Curcumin Complex.Biomolecules · 2021Article
- Bladder cancer cells prevent cisplatin-induced oxidative stress by upregulating Nestin1 expression.American journal of translational research · 2021Article
- Identification of Pannexin 2 as a Novel Marker Correlating with Ferroptosis and Malignant Phenotypes of Prostate Cancer Cells.OncoTargets and therapy · 2020Article
- Ubiquitin-Like Modifier Activating Enzyme 1 as a Novel Diagnostic and Prognostic Indicator That Correlates With Ferroptosis and the Malignant Phenotypes of Liver Cancer Cells.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeNuclear factor (erythroid-derived 2)-like 2, also known as NFE2L2 or NRF2, a transcription factor capable of upregulating antioxidant response element (ARE)-mediated expression and cytoprotective proteins, plays critical roles in chemoprevention, inflammation and aging. NRF2 has recently been proposed as a novel target for cancer chemoprevention. The fungicide miconazole has shown promising antiproliferative effects in cancer cells. MATERIALS AND
methodsAfter miconazole treatment, the p62-KEAP1-NRF2 activation was analyzed by qPCR and Western blot. The nuclear translocation indicating NRF2 activation was further confirmed by immunofluorescence. Finally, the ROS production was detected by CM-H2DCFDA staining.
resultsWe demonstrate in this study that miconazole dramatically increases NRF2 activation in bladder cancer cells, in a dose- and time-dependent manner. Interestingly, levels of expression of p62, a noncanonical pathway that mediates NRF2 activation, appeared to increase in accordance with NRF2. We also investigated levels of the negative regulator kelch-like ECH-associated protein 1 (KEAP1), which is involved in NRF2 activation. As expected, a decrease in KEAP1 expression was found after miconazole exposure. Confirmation of NRF2 nuclear translocation was monitored by immunofluorescence. Miconazole-induced generation of reactive oxygen species (ROS) promoted NRF2 activation. Pretreatment of bladder cancer cells with ROS scavengers abolished NRF2 expression and nuclear translocation, indicating that miconazole activates the noncanonical p62-KEAP1-NRF2 pathway, which is regulated by ROS production.
conclusionOur study elucidates the mechanisms through which miconazole stimulates NRF2 which may contribute to cancer chemopreventive effects.
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