ArticleChemical research in toxicology2018
Curcumin Derivative Epigenetically Reactivates Nrf2 Antioxidative Stress Signaling in Mouse Prostate Cancer TRAMP C1 Cells.
Article in Chemical research in toxicology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 2 of them syntheses that pooled it.
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The trial behind it
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
20 citing papers in PubMed, 2 syntheses or guidelines pooled it, 38 citations in OpenAlex.
- Pooled it
- Phytochemicals in Inhibition of Prostate Cancer: Evidence from Molecular Mechanisms Studies.Biomolecules · 2022Pooled it
- Research on the Mechanism of Natural Products Acting on Chronic Obstructive Pulmonary Disease.Food science & nutrition · 2026Review
- Context-dependent NRF2 signaling in cancer: mechanisms and precision modulation.Molecular biology reports · 2026Review
- Wise as a Serpent and Gentle as a Dove: Pharmacological Targeting of NRF2/KEAP1 Pathway from Treasure Trove of Mother Nature.Drug design, development and therapy · 2026Review
- Nrf2 depletion enhanced curcumin therapy effect in gastric cancer by inducing the excessive accumulation of ROS.Scientific reports · 2024Article
- Review
- NRF2: A crucial regulator for mitochondrial metabolic shift and prostate cancer progression.Frontiers in physiology · 2022Review
- Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress.Frontiers in pharmacology · 2022Review
- The double-edged roles of ROS in cancer prevention and therapy.Theranostics · 2021Review
- Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- Anti-Viral Potential and Modulation of Nrf2 by Curcumin: Pharmacological Implications.Antioxidants (Basel, Switzerland) · 2020Review
- The role of natural products in revealing NRF2 function.Natural product reports · 2020Review
- Pharmacokinetics and pharmacodynamics of three oral formulations of curcumin in rats.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.Frontiers in pharmacology · 2020Review
- Plant Bioactives and the Prevention of Prostate Cancer: Evidence from Human Studies.Nutrients · 2019Review
- Dietary Compounds as Epigenetic Modulating Agents in Cancer.Frontiers in genetics · 2019Review
- The dietary flavone luteolin epigenetically activates the Nrf2 pathway and blocks cell transformation in human colorectal cancer HCT116 cells.Journal of cellular biochemistry · 2018Article
- Targeting Crosstalk between Nrf-2, NF-κB and Androgen Receptor Signaling in Prostate Cancer.Cancers · 2018Review
- Epigenetics of Dietary Phytochemicals in Cancer Prevention: Fact or Fiction.Cancer journal (Sudbury, Mass.)Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-bis-(3,4,5-trimethoxybenzylidene)-tetrahydro-thiopyran-4-one (F10) and (3E,5E)-3,5-bis-(3,4,5-trimethoxy-benzylidene)-tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin, and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways. We performed real-time quantitative PCR and Western blotting to investigate the effects of F10 and E10 on Nrf2, correlated phase II detoxification genes. We also measured expression and activity of DNMTand HDAC enzymes. Enrichment of H3K27me3 on the promoter region of Nrf2 was explored with a chromatin immunoprecipitation (ChIP) assay. Methylation of the CpG region in Nrf2 promoter was doubly examined by bisulfite genomic sequencing (BGS) and methylation DNA immunoprecipitation (MeDIP). Compared with curcumin and SFN, F10 is more potent in activating Nrf2-ARE pathways. Both F10 and E10 enhanced level of Nrf2 and the correlated phase II detoxifying genes. BGS and MeDIP assays indicated that F10 but not E10 hypomethylated the Nrf2 promoter. F10 also downregulated the protein level of DNMT1, DNMT3a, DNMT3b, HDAC1, HDAC4, and HDAC7 and the activity of DNMTs and HDACs. F10 but not E10 effectively reduced the accumulation of H3k27me3 on the promoter of Nrf2. F10 and E10 can activate the Nrf2-ARE pathway and increase the level of Nrf2 and correlated phase II detoxification genes. The reactivation effect on Nrf2 by F10 in TRAMP C1 may come from demethylation, decrease of HDACs, and inhibition of H3k27me3 accumulation.
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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.