ArticleBMB reports2022
DN200434, an orally available inverse agonist of estrogen-related receptor γ, induces ferroptosis in sorafenib-resistant hepatocellular carcinoma.
Article in BMB reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- The role of estrogen and its receptors in the regulation of ferroptosis and autophagy.Molecular biology reports · 2026Review
- PDK4 acts via hippo signaling to inhibit ferroptosis and reduce gemcitabine sensitivity in pancreatic cancer.Journal of molecular histology · 2026Article
- Gradual DNA methylation changes reveal transcription factors implicated in metabolic dysfunction-associated steatotic liver disease progression and epigenetic age acceleration.Clinical epigenetics · 2025Article
- Exploring the Therapeutic Potential of Estrogen-Related Receptor γ Inverse Agonists in Atopic Dermatitis-like Lesions.International journal of molecular sciences · 2025Article
- Deciphering ERR family genes as prognostic and immunological biomarkers through pan-cancer analysis with validation in gallbladder cancer.Frontiers in oncology · 2025Article
- TGFβ2-Driven Ferritin Degradation and Subsequent Ferroptosis Underlie Salivary Gland Dysfunction in Postmenopausal Conditions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair.BMB reports · 2024Article
- Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.Journal of hepatocellular carcinoma · 2024Review
- Unlocking the Potential of Phyto Nanotherapeutics in Hepatocellular Carcinoma Treatment: A Review.Journal of hepatocellular carcinoma · 2024Review
- Engineered small extracellular vesicles loaded with miR-654-5p promote ferroptosis by targeting HSPB1 to alleviate sorafenib resistance in hepatocellular carcinoma.Cell death discovery · 2023Article
- Ferroptosis, Necroptosis, and Pyroptosis in Gastrointestinal Cancers: The Chief Culprits of Tumor Progression and Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- Crosstalk between ferroptosis and steroid hormone signaling in gynecologic cancers.Frontiers in molecular biosciences · 2023Review
- An Inverse Agonist GSK5182 Increases Protein Stability of the Orphan Nuclear Receptor ERRγ via Inhibition of Ubiquitination.International journal of molecular sciences · 2022Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib. [BMB Reports 2022; 55(11): 547-552].
Indexed as
Identifiers
36016501PMC9712702W4299009249What 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.