{
  "abstract": "Statins, inhibitors of 3-hydroxy-3-methylglutaryl CoA reductase, are widely prescribed lipid-lowering agents. Nevertheless, their use is occasionally associated with muscle toxicity, including rhabdomyolysis. Exercise reportedly exacerbates statin-induced muscle injury; however, the underlying mechanisms remain poorly understood. Here, we investigated the role of protein kinase C (PKC) signaling in the development of statin-induced cytotoxicity using a rhabdomyosarcoma-derived cell line (RD cells), with particular emphasis placed on the regulation of monocarboxylate transporter 4 (MCT4), a lactate transporter implicated in intracellular acidification and cytotoxic responses. Treatment with simvastatin, atorvastatin, and fluvastatin reduced RD cell viability in a concentration-dependent manner. Co-treatment with bisindolylmaleimide I (BIM), an inhibitor of PKCα, β, γ, δ, and ε, attenuated statin-induced cytotoxicity and tended to suppress simvastatin-induced MCT4 upregulation. Furthermore, co-treatment with Gö6976, a selective inhibitor of PKCα and β, did not mitigate the simvastatin-induced reduction in cell viability. Small interfering RNA-mediated knockdown of PKCδ significantly rescued simvastatin-induced cytotoxicity. Tamoxifen, a clinically available drug with PKC inhibitory activity, including against the δ isoform, attenuated simvastatin-induced cell injury, paralleling the effects of BIM. Collectively, our findings demonstrate that PKCδ contributes to statin-induced cytotoxicity in rhabdomyosarcoma cells, at least in part by regulating MCT4 expression.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Keisuke Okamoto"
    },
    {
      "name": "Toya Matsui"
    },
    {
      "name": "Yurika Kikutani"
    },
    {
      "name": "Hinata Ueda"
    },
    {
      "name": "Ayako Furugen"
    },
    {
      "name": "Katsuya Narumi"
    },
    {
      "name": "Masaki Kobayashi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fn6nw3zrmfbs5.bib",
  "cited_by": 0,
  "doi": "10.1248/bpb.b25-00680",
  "fulltext_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b25-00680/_article",
  "id": "fn6nw3zrmfbs5",
  "issns": [
    "1347-5215",
    "0918-6158"
  ],
  "landing_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b25-00680/_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",
      "1306|Cancer, Lipids, and Metabolism"
    ]
  ],
  "openalex": "W7208735980",
  "pdf_url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b25-00680/_pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fn6nw3zrmfbs5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:32Z",
      "native_id": "10.1248/bpb.b25-00680",
      "source": "jstage",
      "url": "https://www.jstage.jst.go.jp/article/bpb/49/9/49_b25-00680/_article"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Lipids, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Involvement of Protein Kinase C Delta and Monocarboxylate Transporter 4 in the Development of Statin-Induced Cytotoxicity in a Rhabdomyosarcoma-Derived Cell Line",
  "title_text": "Involvement of Protein Kinase C Delta and Monocarboxylate Transporter 4 in the Development of Statin-Induced Cytotoxicity in a Rhabdomyosarcoma-Derived Cell Line",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:32Z",
  "url": "https://research.draconitic.com/paper/fn6nw3zrmfbs5",
  "venue": "Biological and Pharmaceutical Bulletin",
  "versions": []
}