ArticlePloS one2016
Cytochrome P450 1A2 Metabolizes 17β-Estradiol to Suppress Hepatocellular Carcinoma.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Synthesis and Antitumor Potency of 2International journal of molecular sciences · 2026Article
- Multi-omics analysis of key lipid metabolism-related genes involved in the anti-hepatocellular carcinoma effect of dihydroartemisinin.Discover oncology · 2026Article
- Regulation of Mitochondrial and Peroxisomal Metabolism in Female Obesity and Type 2 Diabetes.International journal of molecular sciences · 2024Review
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- Testosterone, β-estradiol, and hepatocellular carcinoma: stimulation or inhibition? A comparative effect analysis on cell cycle, apoptosis, and Wnt signaling of HepG2 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Sphingosine kinase 2 and p62 regulation are determinants of sexual dimorphism in hepatocellular carcinoma.Molecular metabolism · 2024Article
- Hepatocellular Carcinoma Incidence and Mortality in the USA by Sex, Age, and Race: A Nationwide Analysis of Two Decades.Journal of clinical and translational hepatology · 2024Article
- The complex biology of aryl hydrocarbon receptor activation in cancer and beyond.Biochemical pharmacology · 2023Review
- The role of NLRP3 inflammasome in hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- The dual role of transforming growth factor-beta signatures in human B viral multistep hepatocarcinogenesis: early and late responsive genes.Journal of liver cancer · 2022Article
- Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway.International journal of molecular sciences · 2022Article
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- Estrogen Receptor-α Suppresses Liver Carcinogenesis and Establishes Sex-Specific Gene Expression.Cancers · 2021Article
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- Effects of Short- and Long-Term Soy Protein Feeding on Hepatic Cytochrome P450 Expression in Obese Nonalcoholic Fatty Liver Disease Rat Model.Frontiers in nutrition · 2021Article
- Integrative Analysis of Epigenome and Transcriptome Data Reveals Aberrantly Methylated Promoters and Enhancers in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Biological roles of cytochrome P450 1A1, 1A2, and 1B1 enzymes.Archives of pharmacal research · 2021Review
- Anti-Hepatocellular Carcinoma Effect and Molecular Mechanism of the Estrogen Signaling Pathway.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) occurs more frequently in men than in women. It is commonly agreed that estrogen plays important roles in suppressing HCC development, however, the underlying mechanism remains largely unknown. Since estrogen is mainly metabolized in liver and its metabolites affect cell proliferation, we sought to investigate if the liver-specific cytochrome P450 1A2 (CYP1A2) mediated the inhibitory effect of estrogen on HCC. In this study, the expression of estrogen-metabolizing enzyme CYP1A2 was determined in HCC tissues and cell lines. Cell proliferation and apoptosis were assessed in cells with or without CYP1A2 overexpression. The levels of 17β-estradiol (E2) and its metabolite 2-methoxyestradiol (2-ME) were determined. A xenograft tumor model in mice was established to confirm the findings. It was found that CYP1A2 expression was greatly repressed in HCC. E2 suppressed HCC cell proliferation and xenograft tumor development by inducing apoptosis. The inhibitory effect was significantly enhanced in cells with CYP1A2 overexpression, which effectively conversed E2 to the cytotoxic 2-ME. E2 in combination with sorafenib showed an additive effect on HCC. The anti-HCC effect of E2 was not associated with estrogen receptors ERα and ERβ as well as tumor suppressor P53 but enhanced by the approved anti-HCC drug sorafenib. In addition, HDAC inhibitors greatly induced CYP1A2 promoter activities in cancer cells, especially liver cancer cells, but not in non-tumorigenic cells. Collectively, CYP1A2 metabolizes E2 to generate the potent anti-tumor agent 2-ME in HCC. The reduction of CYP1A2 significantly disrupts this metabolic pathway, contributing the progression and growth of HCC and the gender disparity of this malignancy.
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