{
  "abstract": "Background: Primary liver cancer is the sixth most commonly diagnosed cancer and the third most common cause of cancer death worldwide. Chansu is made by processing and drying the white serous fluid of the posterior ear and skin glands of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider. Chansu is a well-known traditional Chinese medicine (TCM) that is mainly used for detoxification, detumescence, analgesia, the treatment of cancer, and heart failure. Cinobufagin, as a bufadienolide, has been reported as the main antitumor active component of Chansu. However, the molecular mechanisms related to the anticancer effects of cinobufagin still remain elusive.\n\nPurpose: The purpose of this study is to explore whether cinobufagin inhibits the growth of HepG2 and SK-HEP-1 tumor cells by inducing peroxisome dysfunction and interfering with lipid metabolism.\n\nMethods: The protein levels of catalase, ABCD3, PEX5, PEX6, and PEX10 in human hepatoma cells were analyzed by Western blotting. The effects of cinobufagin on the viability of HepG2 and SK-HEP-1 cells were detected by cell counting kit-8 (CCK-8) assay and clone formation assay. Small interfering RNA (siRNA) transfection was used to explore whether inhibition of PEX could enhance the inhibitory effect of cinobufagin on cell growth of HepG2 and SK-HEP-1 tumor cells. The effects of cinobufagin on lipid metabolism were analyzed by untargeted metabolomics. The in vivo antitumor effects of cinobufagin were verified by animal studies.\n\nResults: Cinobufagin causes peroxisome dysfunction in HepG2 and SK-HEP-1 tumor cells. From a mechanistic point of view, we reveal that cinobufagin downregulates the expression of PEX5, PEX10, and PEX6. In addition, through RNA interference, cinobufagin partially blocks the growth of HepG2 and SK-HEP-1 tumor cells and restrains the expression of lipid metabolism-related proteins via downregulating the expression of PEX5 and PEX10. Subsequently, we perform a non-targeted metabolomics analysis of the cells and find that cinobufagin exerts its anti-hepatoma effects by interfering with lipid metabolic reprogramming. The results show that cinobufagin mainly interferes with glycerophospholipid and fatty acyl levels. In addition, in vivo experiments reveal that cinobufagin restrains tumor growth without obvious adverse effects. Serum metabolomics analyses reveal that cinobufagin causes significant changes in the levels of lipid and lipid-like differential metabolites.\n\nConclusion: Cinobufagin is a promising natural drug for the treatment of liver cancer, and PEXs may be potential molecular targets of cinobufagin to exert anticancer effects. Cinobufagin induces peroxisome dysfunction through suppression of the proteins encoded by the PEX genes and interferes with lipid metabolism to restrain the growth of liver cancer cells.",
  "abstract_shown": true,
  "affiliations": [
    "Shandong Medical and Pharmaceutical University",
    "Qingdao Central Hospital, University of Health and Rehabilitation Sciences"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jingyi Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wanjun Shao"
    },
    {
      "affs": [
        0
      ],
      "name": "Congying Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Qi Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "Rufei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoqian Rong"
    },
    {
      "affs": [
        0
      ],
      "name": "Ailin Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6tkdhaqg92sk4.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1860569",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13720286/?tool=EBI",
  "id": "6tkdhaqg92sk4",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1860569/full",
  "language": "eng",
  "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": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1306|Cancer, Lipids, and Metabolism"
    ]
  ],
  "openalex": "W7222699273",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1860569/pdf",
  "pmcid": "PMC13720286",
  "pmid": "42964345",
  "published": "2026-10-16",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/6tkdhaqg92sk4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1860569",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1860569/full"
    },
    {
      "first_seen": "2026-10-31T12:21:36Z",
      "native_id": "PMC:PMC13720286",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13720286"
    },
    {
      "first_seen": "2026-11-03T12:21:12Z",
      "native_id": "PMC13720286",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fphar.2026.1860569"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Lipids, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Cinobufagin induces peroxisome dysfunction through suppression of the peroxisomal biogenesis factor proteins and interferes with lipid metabolism to affect the growth of liver cancer cells",
  "title_text": "Cinobufagin induces peroxisome dysfunction through suppression of the peroxisomal biogenesis factor proteins and interferes with lipid metabolism to affect the growth of liver cancer cells",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:21:12Z",
  "url": "https://research.draconitic.com/paper/6tkdhaqg92sk4",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}