{
    "abstract": "The purpose of the study was to elucidate the role of the Bcl-2 family of proteins in mediating cisplatin resistance in oral squamous cell carcinoma (OSCC). The value of the BH3-mimetics venetoclax and obatoclax as sensitisers for cisplatin treatment in OSCC was also evaluated.\nIn this study the expression levels of a series of pro- and anti-apoptotic members of the Bcl-2 family in paired cisplatin-sensitive (SCC4) and resistant (SCC4cisR) tongue squamous carcinoma cell lines were examined by western blotting. The apoptotic rate induced by cisplatin and BH3-mimetics venetoclax and obatoclax alone or in combination in OSCC was also evaluated by Annexin V/Propidium Iodide double-stained flow cytometric assays.\nObatoclax was shown to synergistically enhance cisplatin-induced apoptosis, and this enhancement was associated with a marked degradation in pro-survival Mcl-1 and upregulation in conformationally active form of pro-apoptotic Bak.\nOur study presents novel insights into the relationship between the Bcl-2 family and cisplatin efficacy in OSCC. It also demonstrates that targeted therapy with BH-3 mimetics, such as obatoclax, may represent a new strategy for OSCC therapy.",
    "authors": [
        {
            "affiliation": "School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. Electronic address: gaot@tcd.ie.",
            "firstname": "Tianyi",
            "initials": "T",
            "lastname": "Gao"
        },
        {
            "affiliation": "School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.",
            "firstname": "Stefania",
            "initials": "S",
            "lastname": "Magnano"
        },
        {
            "affiliation": "School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.",
            "firstname": "Molly",
            "initials": "M",
            "lastname": "Quadros"
        },
        {
            "affiliation": "School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.",
            "firstname": "Patricia Hannon",
            "initials": "PH",
            "lastname": "Barroeta"
        },
        {
            "affiliation": "School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.",
            "firstname": "Daniela M",
            "initials": "DM",
            "lastname": "Zisterer"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025. Published by Elsevier Ltd.",
    "doi": "10.1016/j.archoralbio.2025.106250",
    "journal": "Archives of oral biology",
    "keywords": [
        "Apoptosis",
        "BH-3 mimetics",
        "Bcl-2 family",
        "Chemoresistance",
        "Mcl-1",
        "Oral squamous cell carcinoma"
    ],
    "methods": null,
    "publication_date": "2025-04-08",
    "pubmed_id": "40194355",
    "results": "Obatoclax was shown to synergistically enhance cisplatin-induced apoptosis, and this enhancement was associated with a marked degradation in pro-survival Mcl-1 and upregulation in conformationally active form of pro-apoptotic Bak.",
    "title": "The pan-BH-3 mimetic, obatoclax, synergistically enhances cisplatin-induced apoptosis in oral squamous cell carcinoma through a mechanism that involves degradation of the pro-survival protein Mcl-1.",
    "xml": "<Element 'PubmedArticle' at 0x788503b055d0>"
}