{
  "abstract": "Realgar (As4S4) has long been used in traditional medicine, yet its clinical application remains limited due to poor bioavailability and toxicity. Realgar transforming solution (RTS), a bioleached product generated through microbial transformation of realgar, exhibits enhanced anti-tumor activity; however, its underlying mechanism remains unclear. This study investigated whether ferroptosis contributes to the anti-leukemic effects of RTS in NB4 cells, focusing on iron homeostasis and the solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) antioxidant axis. NB4 cells were treated with RTS, arsenic trioxide (ATO), or realgar, and cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Transcriptomic profiling, biochemical assays, fluorescence probes, flow cytometry, and Western blotting were employed to evaluate ferroptosis-related changes. RTS inhibited NB4 cell viability more effectively than ATO or realgar at comparable arsenic concentrations. Transcriptomic analysis indicated significant enrichment of ferroptosis-related pathways. RTS decreased glutathione and superoxide dismutase levels, increased malondialdehyde accumulation and lipid peroxidation, disrupted mitochondrial membrane potential, and elevated intracellular total iron and mitochondrial Fe2+ levels. Additionally, RTS downregulated SLC7A11 and GPX4 and altered the expression of iron metabolism-related proteins, including transferrin receptor protein 1, nuclear receptor coactivator 4, ferritin heavy chain 1, ferroportin 1, iron-responsive element-binding protein 2, and heme oxygenase 1. Moreover, ferrostatin-1 and deferoxamine mesylate partially rescued RTS-induced cytotoxicity and alleviated oxidative damage and iron overload. These results indicate that RTS induces ferroptosis-associated cell death in NB4 cells by disrupting iron homeostasis and inhibiting the SLC7A11/GPX4 axis, supporting further investigation of RTS as a modernized arsenic-based anti-leukemic formulation.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Zhaorong Yue"
    },
    {
      "name": "Qinghong Liu"
    },
    {
      "name": "Yanni Wang"
    },
    {
      "name": "Ruyue Wang"
    },
    {
      "name": "Zhongqing Li"
    },
    {
      "name": "Manjie Xu"
    },
    {
      "name": "Piao Luo"
    },
    {
      "name": "Jiaxuan Li"
    },
    {
      "name": "Jiawen Xu"
    },
    {
      "name": "Wenjun Xu"
    },
    {
      "name": "Weizhong Zhang"
    },
    {
      "name": "Jianing He"
    },
    {
      "name": "Jiayi Chen"
    },
    {
      "name": "Shahab Uddin"
    },
    {
      "name": "Yang Li"
    },
    {
      "name": "Xin Wang"
    },
    {
      "name": "Hongyu Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ep90a29ctsjce.bib",
  "cited_by": 0,
  "doi": "10.1248/bpb.b26-00225",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00225/_article",
  "id": "ep90a29ctsjce",
  "issns": [
    "1347-5215",
    "0918-6158"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00225/_article",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "jstage-journal",
      "medicine/pharmacology-toxicology"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7212036923",
  "pdf_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00225/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/ep90a29ctsjce.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:32Z",
      "native_id": "10.1248/bpb.b26-00225",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00225/_article"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "jstage-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Realgar Transforming Solution Triggers Ferroptosis-Associated Death in NB4 Leukemia Cells through Disruption of Iron Homeostasis and Suppression of the SLC7A11/GPX4 Axis",
  "title_text": "Realgar Transforming Solution Triggers Ferroptosis-Associated Death in NB4 Leukemia Cells through Disruption of Iron Homeostasis and Suppression of the SLC7A11/GPX4 Axis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:32Z",
  "url": "https://research.draconitic.com/paper/ep90a29ctsjce",
  "venue": "Biological and Pharmaceutical Bulletin",
  "versions": []
}