{
  "abstract": "Ferroptosis is an iron-dependent form of regulated cell death, and its resistance represents a major obstacle in cancer therapy. In this study, we evaluated the responsiveness of human lung and renal cancer cell lines to ferroptosis inducers and investigated whether pharmacological inhibition of ataxia-telangiectasia mutated (ATM) kinase could overcome ferroptosis resistance. While A549, ACHN, and Caki-1 cells exhibited dose-dependent sensitivity to erastin, RSL3, and FIN56, PC-9 and Caki-2 cells were relatively resistant. Notably, pharmacological inhibition of ATM using KU-55933 significantly sensitized these resistant cells to all tested ferroptosis inducers. This combinatorial treatment induced a DNA damage response, as evidenced by increased γ-H2AX expression, and reduced cell viability in a ferroptosis-dependent manner, which was reversed by ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) or an iron chelator, deferoxamine. Mechanistically, ATM inhibition disrupted glutathione (GSH) homeostasis in resistant cells. Although single treatments had minimal effects, the combination of erastin and KU-55933 led to a marked depletion of total GSH and reduced GSH, an increase in oxidized glutathione (GSSG), and a significant reduction in the GSH/GSSG ratio. These findings indicate that ATM inhibition promotes ferroptosis by impairing redox balance rather than directly modulating ferroptosis-inducing pathways. Collectively, our results demonstrate that pharmacological ATM inhibition by KU-55933 overcomes ferroptosis resistance by inducing a DNA damage response and disrupting GSH-dependent redox homeostasis. Targeting ATM may represent a promising therapeutic strategy to sensitize resistant cancers to ferroptosis-based treatments.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "Muhammad Irshad Farooq"
    },
    {
      "name": "Mahiro Uozumi"
    },
    {
      "name": "Sisca Ucche"
    },
    {
      "name": "Hiroshi Kitamura"
    },
    {
      "name": "So-Ichiro Sasaki"
    },
    {
      "name": "Yoshihiro Hayakawa"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5mymq4n49gtce.bib",
  "cited_by": 0,
  "doi": "10.1248/bpb.b26-00309",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00309/_article",
  "id": "5mymq4n49gtce",
  "issns": [
    "1347-5215",
    "0918-6158"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00309/_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": "W7223963390",
  "pdf_url": "https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00309/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5mymq4n49gtce.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:32Z",
      "native_id": "10.1248/bpb.b26-00309",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00309/_article"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "jstage-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "ATM Inhibitor KU-55933 Overcomes Ferroptosis-Resistance in Human Cancer Cell Lines",
  "title_text": "ATM Inhibitor KU-55933 Overcomes Ferroptosis-Resistance in Human Cancer Cell Lines",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:32Z",
  "url": "https://research.draconitic.com/paper/5mymq4n49gtce",
  "venue": "Biological and Pharmaceutical Bulletin",
  "versions": []
}