ArticleThe AAPS journal2014
Blocking of JB6 cell transformation by tanshinone IIA: epigenetic reactivation of Nrf2 antioxidative stress pathway.
Article in The AAPS journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Research on the Mechanism of Natural Products Acting on Chronic Obstructive Pulmonary Disease.Food science & nutrition · 2026Review
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- HDAC3-driven immunometabolic reprogramming in type 2 diabetes and its complications: from enzymatic deacetylation to non-enzymatic scaffolding.Frontiers in immunology · 2026Review
- Micro- and Nanoplastics and Functional Nutrients in Human Health: Epigenetic Mechanisms and Cellular Resilience Signaling in Brain Insulin Resistance and the Risk of Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway.Cell death discovery · 2024Article
- Review
- Review
- Coenzyme Q10 treatment and diazinon exposure in parental male rats: effects of the exposure on their neonatal brains.Toxicology research · 2023Article
- A New Frontier in Studying Dietary Phytochemicals in Cancer and in Health: Metabolic and Epigenetic Reprogramming.Preventive nutrition and food science · 2022Review
- Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.Molecules (Basel, Switzerland) · 2022Review
- Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress.Frontiers in pharmacology · 2022Review
- Review
- Effects of the Phytochemical Combination PB123 on Nrf2 Activation, Gene Expression, and the Cholesterol Pathway in HepG2 Cells.OBM integrative and complimentary medicine · 2022Article
- Anticancer mechanisms of phytochemical compounds: focusing on epigenetic targets.Environmental science and pollution research international · 2021Review
- Tanshinone for polycystic ovary syndrome: A protocol of systematic review and meta-analysis.Medicine · 2021Article
- NRF2-Related Epigenetic Modifications in Cardiac and Vascular Complications of Diabetes Mellitus.Frontiers in endocrinology · 2021Review
- Epigenetic Studies of Chinese Herbal Medicine: Pleiotropic Role of DNA Methylation.Frontiers in pharmacology · 2021Review
- The Anti-Inflammatory Properties of Phytochemicals and Their Effects on Epigenetic Mechanisms Involved in TLR4/NF-κB-Mediated Inflammation.Frontiers in immunology · 2021Review
- UV-type specific alteration of miRNA expression and its association with tumor progression and metastasis in SCC cell lines.Journal of cancer research and clinical oncology · 2020Article
- Epigenetic Regulation of NRF2/KEAP1 by Phytochemicals.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing numbers of natural products have been found to possess anticancer effects. Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master regulator of the antioxidative stress response, and our previous studies found that epigenetic modification of the Nrf2 gene appears to be a critical mechanism. Salvia miltiorrhiza, a Chinese herbal medicine widely used in Asian countries, has been shown to possess anticancer and antioxidant effects. Tanshinone IIA (TIIA), an active component in S. miltiorrhiza, has been reported to activate Nrf2 pathway. The objective of this study was to investigate the epigenetic regulation of Nrf2 by TIIA in mouse skin epidermal JB6 cells and the functional consequences for cell transformation. TIIA was found to induce antioxidant response element-luciferase and upregulate the mRNA and protein levels of Nrf2 and Nrf2 downstream target genes HO-1 and NQO-1. TIIA decreased the colony formation of JB6 cells by approximately 80%. TIIA decreased the protein levels of DNMT1, DNMT3a, DNMT3b, and HDAC3 and inhibited the enzymatic activity of HDACs. Bisulfite genomic sequencing indicated that TIIA demethylated the first five CpGs in the promoter region of the Nrf2 gene. Chromatin immunoprecipitation assays showed that TIIA treatment increased the recruitment of RNA polymerase II at Nrf2 transcription start site but had limited effects on enrichment of Ac-H3 in Nrf2 promoter. Taken together, our results show that TIIA activates the Nrf2 signaling pathway and induces epigenetic demethylation of the CpGs of Nrf2. The epigenetic reactivation of the Nrf2 signaling pathway by TIIA could potentially contribute to the attenuation of JB6 cellular transformation and anticancer effects.
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