{
  "abstract": "BackgroundLung cancer remains the leading cause of cancer-related mortality worldwide, its 5-year survival rate continues to be unsatisfactory. Current therapies are often limited by resistance, toxicity, or poor efficacy, highlighting the urgent need for novel strategies.MethodWe performed a high-throughput compound screen for inducing cell death in non-small cell lung cancer (NSCLC) cells. Combined with lactate dehydrogenase (LDH) release assays, cell death morphology observation, and propidium iodide (PI) staining, we confirmed the cell death mode as pyroptosis. Then, we conducted a genome-wide CRISPR/Cas9 screen to identify the critical regulator of compound-induced pyroptosis.ResultsThe screening results showed that morusin is a trigger of gasdermin E (GSDME)-mediated pyroptosis in non-small cell lung cancer (NSCLC) cells. Importantly, morusin suppresses tumor growth in vivo. Through a genome-wide CRISPR/Cas9 screen, we further demonstrated that angiotensin II receptor type 2 (AGTR2) as a critical regulator of morusin-induced pyroptosis, acting via activation of the caspase-3–GSDME signaling cascade. Notably, morusin also upregulated AGTR2 expression in NSCLC cells. In an NSCLC mouse model, morusin treatment potently suppressed wild-type tumor growth, whereas its antitumor efficacy was substantially diminished in AGTR2-knockout tumors.ConclusionOur study reveals a novel mechanism underlying the antitumor effect of morusin, establishes AGTR2 as a potential therapeutic target, and provides a rationale for pyroptosis-based therapy for NSCLC.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Xiaoyue Cui"
    },
    {
      "name": "Qiqi Zhang"
    },
    {
      "name": "Junjie Hu"
    },
    {
      "name": "Xun Li"
    },
    {
      "name": "Chengjie Shu"
    },
    {
      "name": "Yixuan Xi"
    },
    {
      "name": "Shiqi Zheng"
    },
    {
      "name": "Shiyao Ma"
    },
    {
      "name": "Fan Li"
    },
    {
      "name": "Xinpeng Bai"
    },
    {
      "name": "Ganglu Liu"
    },
    {
      "name": "Hong Zhang"
    },
    {
      "name": "Wanyan Deng"
    },
    {
      "name": "Mengjun Bie"
    },
    {
      "name": "Huansha Yu"
    },
    {
      "name": "Dandan Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8zr2yhtg36rk2.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1970372",
  "fulltext_url": null,
  "id": "8zr2yhtg36rk2",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1970372",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "medicine/pharmacology-toxicology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/8zr2yhtg36rk2.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:20:47Z",
      "native_id": "10.3389/fphar.2026.1970372",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1970372"
    },
    {
      "first_seen": "2026-11-06T12:21:21Z",
      "native_id": "10.3389/fphar.2026.1970372",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1970372/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "feed-journal:medicine/pharmacology-toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Morusin induces GSDME-dependent pyroptosis in non-small cell lung cancer via the angiotensin II receptor type 2",
  "title_text": "Morusin induces GSDME-dependent pyroptosis in non-small cell lung cancer via the angiotensin II receptor type 2",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T00:23:04Z",
  "url": "https://research.draconitic.com/paper/8zr2yhtg36rk2",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}