{
  "abstract": "FLLL32 is a curcumin analogue with reported anti-tumor activity, mainly through inhibition of signal transducer and activator of transcription 3 (STAT3) signaling and induction of apoptosis. However, whether FLLL32 regulates ferroptosis in colorectal cancer (CRC) and the underlying mechanism remain unclear. Here, using a patient-derived CRC organoid screening platform, we identified FLLL32 as a potent anti-CRC compound. FLLL32 suppressed CRC organoid growth, inhibited CRC cell proliferation and migration in vitro, and inhibited xenograft tumor growth in vivo. In parallel, FLLL32 induced ferroptosis-associated iron accumulation, reactive oxygen species (ROS) production, lipid peroxidation, mitochondrial morphological and functional abnormalities. The ferroptosis inhibitor Ferrostatin-1 markedly restored FLLL32-impaired cell viability and reduced ROS, whereas the apoptosis inhibitor Z-VAD-FMK showed weaker protection. These findings suggest that ferroptosis is a major contributor to FLLL32-induced cell death, although apoptotic features are also present. Mechanistically, FLLL32 interacted with STAT3, and Glu638 and Met726 contributed to the FLLL32-STAT3 interaction. FLLL32 also suppressed STAT3 Tyr705 phosphorylation and nuclear signaling, thereby disrupting pSTAT3-mediated transcriptional regulation of glutathione peroxidase 4 (GPX4) and solute carrier family 40 member 1 (SLC40A1), weakening lipid peroxide detoxification and cellular iron efflux, promoting intracellular iron accumulation, and enhancing ferroptosis in CRC cells. These findings define a STAT3-GPX4/SLC40A1-dependent mechanism underlying the anti-CRC activity of FLLL32 and support further investigation of STAT3-associated ferroptosis regulation as a potential therapeutic vulnerability in CRC.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China.",
    "Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China.",
    "Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China. yangxuyang@wchscu.cn.",
    "Laboratory of Gastrointestinal Tumor Epigenetics and Genomics, State Key Laboratory of Biotherapy and Cancer Center, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China. hjunhong@scu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tong Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengqiu Hao"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiuye Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "Sicheng Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaguang Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yang Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Xuyang Yang"
    },
    {
      "affs": [
        3
      ],
      "name": "Junhong Han"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/45gtvy37dv0kg.bib",
  "cited_by": 0,
  "doi": "10.1186/s43556-026-00575-5",
  "fulltext_url": "https://europepmc.org/articles/PMC13683295",
  "id": "45gtvy37dv0kg",
  "issns": [
    "2662-8651"
  ],
  "landing_url": "https://europepmc.org/article/MED/42900324",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7222941152",
  "pdf_url": "https://europepmc.org/articles/PMC13683295?pdf=render",
  "pmcid": "PMC13683295",
  "pmid": "42900324",
  "published": "2026-10-20",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/45gtvy37dv0kg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:32Z",
      "native_id": "MED:42900324",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42900324"
    },
    {
      "first_seen": "2026-10-30T13:45:33Z",
      "native_id": "334a77a8d5a14daabbd2e8e86ef47aab",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s43556-026-00575-5"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Ferroptosis and cancer prognosis",
      "subfield": "general"
    }
  ],
  "title": "Curcumin analogue FLLL32 induces ferroptosis by targeting the STAT3-GPX4/SLC40A1 axis in colorectal cancer.",
  "title_text": "Curcumin analogue FLLL32 induces ferroptosis by targeting the STAT3-GPX4/SLC40A1 axis in colorectal cancer.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:33Z",
  "url": "https://research.draconitic.com/paper/45gtvy37dv0kg",
  "venue": "Molecular biomedicine",
  "versions": []
}