{
  "abstract": "Gastric cancer is one of the most malignant cancers in the world, posing a significant threat to human life and persisting as a major clinical challenge. Cyclovirobuxine D (CVB-D), derived from boxwood and traditionally employed in cardiovascular disease treatment, has emerged as a promising candidate for cancer therapy. However, its mechanism of action still needs to be clearly defined. We aimed to comprehensively evaluate CVB-D's impact on gastric cancer and elucidate its underlying mechanisms. Here, we found CVB-D induced excessive endo-lysophagy in gastric cancer. Moreover, subsequent experimental analyses revealed that CVB-D directly engages the ATPase H+ transporting V0 subunit a1 (ATP6V0A1)-containing V-ATPase complex and perturbs endo-lysosomal homeostasis, leading to abnormal lysosomal acidification, impaired lysosomal protease activity, and autophagic flux blockade. Mechanistically, damaged endo-lysosomes recruited the autophagic adaptor P62/sequestosome 1 (SQSTM1) in a galectin8 (Gal8)-dependent manner, ultimately triggering endoplasmic reticulum (ER) stress and apoptosis in gastric cancer cells. Furthermore, through cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models, we validated the therapeutic efficacy of CVB-D against gastric cancer. Notably, CVB-D enhances the sensitivity of gastric cancer to the chemotherapeutic agent cisplatin. Our findings suggest that CVB-D holds promise as an effective therapeutic agent for gastric cancer treatment.",
  "abstract_shown": true,
  "affiliations": [
    "State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing, 400716, China",
    "Department of Dermatology, The Third Hospital of Hebei Medical University, Shijiazhuang, 050051, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Chongyang Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Minghao Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yacong Ji"
    },
    {
      "affs": [
        0
      ],
      "name": "Chaowei Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Sicheng Wan"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangfei Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Kui Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Erhu Zhao"
    },
    {
      "affs": [
        0
      ],
      "name": "Guangzhao Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Xin Hu"
    },
    {
      "affs": [
        0
      ],
      "name": "Changhong Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Haoyan Ji"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaosong Hu"
    },
    {
      "affs": [
        1
      ],
      "name": "Shaomin Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongjuan Cui"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b4bw212emhrss.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jpha.2026.101672",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13742328/?tool=EBI",
  "id": "b4bw212emhrss",
  "issns": [
    "2095-1779",
    "2214-0883"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13742328",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "1307|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7162437510",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13742328/pdf/?tool=EBI",
  "pmcid": "PMC13742328",
  "pmid": "42997595",
  "published": "2026-05-26",
  "publisher": "Xi'an Jiaotong University",
  "ris": "https://research.draconitic.com/paper/b4bw212emhrss.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "PMC:PMC13742328",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13742328"
    },
    {
      "first_seen": "2026-11-10T12:23:11Z",
      "native_id": "PMC13742328",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jpha.2026.101672"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Autophagy in Disease and Therapy",
      "subfield": "cell-biology"
    }
  ],
  "title": "Cyclovirobuxine D suppresses gastric cancer growth by targeting the V-ATPase complex and inducing excessive endo-lysophagy",
  "title_text": "Cyclovirobuxine D suppresses gastric cancer growth by targeting the V-ATPase complex and inducing excessive endo-lysophagy",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T12:23:11Z",
  "url": "https://research.draconitic.com/paper/b4bw212emhrss",
  "venue": "Journal of pharmaceutical analysis",
  "versions": []
}