ArticlePloS one2016
Estradiol and Estrogen Receptor Agonists Oppose Oncogenic Actions of Leptin in HepG2 Cells.
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.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Intratumoral but not circulating estradiol predicts postoperative survival in men with hepatocellular carcinoma.Discover oncology · 2026Article
- Gastrointestinal cancers in women: The role of sex hormones.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2026Review
- Pro-inflammatory effects of endogenous and recombinant MDA-7/IL-24 with RGD peptide on human hepatic stellate cells.Scientific reports · 2025Article
- Identification and validation of PANoptosis-related LncRNAs prognosis system in hepatocellular carcinoma.Scientific reports · 2025Article
- Gender dimorphism in hepatocarcinogenesis-DNA methylation modification regulated X-chromosome inactivation escape molecule XIST.Clinical and translational medicine · 2023Article
- Review
- Cytoprotective, Antiproliferative, and Anti-Oxidant Potential of the Hydroethanolic Extract ofToxins · 2023Article
- Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review.Molecules (Basel, Switzerland) · 2022Review
- Modulation of SOCS3 Levels via STAT3 and Estrogen-ERαp66 Signaling during Hepatitis E Virus Replication in Hepatocellular Carcinoma Cells.Journal of virology · 2022Article
- Therapeutic Value of Estrogen Receptor α in Hepatocellular Carcinoma Based on Molecular Mechanisms.Journal of clinical and translational hepatology · 2022Review
- A Multi-Omics Study Revealing the Metabolic Effects of Estrogen in Liver Cancer Cells HepG2.Cells · 2021Article
- Nuclear ErbB2 expression in hepatocytes in liver disease.Virchows Archiv : an international journal of pathology · 2021Article
- Anti-Hepatocellular Carcinoma Effect and Molecular Mechanism of the Estrogen Signaling Pathway.Frontiers in oncology · 2021Review
- Role of G Protein-Coupled Estrogen Receptor in Digestive System Carcinomas: A Minireview.OncoTargets and therapy · 2021Review
- GPER-Induced ERK Signaling Decreases Cell Viability of Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Unraveling the Role of Leptin in Liver Function and Its Relationship with Liver Diseases.International journal of molecular sciences · 2020Review
- Estrogen-induced epigenetic silencing ofEpigenetics · 2020Article
- Article
- The Bisphenol A Induced Oxidative Stress in Non-Alcoholic Fatty Liver Disease Male Patients: A Clinical Strategy to Antagonize the Progression of the Disease.International journal of environmental research and public health · 2020Article
- Sex Hormone-Dependent Physiology and Diseases of Liver.International journal of environmental research and public health · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Obesity is a significant risk factor for certain cancers, including hepatocellular carcinoma (HCC). Leptin, a hormone secreted by white adipose tissue, precipitates HCC development. Epidemiology data show that men have a much higher incidence of HCC than women, suggesting that estrogens and its receptors may inhibit HCC development and progression. Whether estrogens antagonize oncogenic action of leptin is uncertain. To investigate potential inhibitory effects of estrogens on leptin-induced HCC development, HCC cell line HepG2 cells were treated with leptin in combination with 17 β-estradiol (E2), estrogen receptor-α (ER-α) selective agonist PPT, ER-β selective agonist DPN, or G protein-coupled ER (GPER) selective agonist G-1. Cell number, proliferation, and apoptosis were determined, and leptin- and estrogen-related intracellular signaling pathways were analyzed. HepG2 cells expressed a low level of ER-β mRNA, and leptin treatment increased ER-β expression. E2 suppressed leptin-induced HepG2 cell proliferation and promoted cell apoptosis in a dose-dependent manner. Additionally E2 reversed leptin-induced STAT3 and leptin-suppressed SOCS3, which was mainly achieved by activation of ER-β. E2 also enhanced ERK via activating ER-α and GPER and activated p38/MAPK via activating ER-β. To conclude, E2 and its receptors antagonize the oncogenic actions of leptin in HepG2 cells by inhibiting cell proliferation and stimulating cell apoptosis, which was associated with reversing leptin-induced changes in SOCS3/STAT3 and increasing p38/MAPK by activating ER-β, and increasing ERK by activating ER-α and GPER. Identifying roles of different estrogen receptors would provide comprehensive understanding of estrogenic mechanisms in HCC development and shed light on potential treatment for HCC patients.
Indexed as
Identifiers
What OpenQuestion holds
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.