{
  "abstract": "Head and neck squamous cell carcinoma (HNSCC) accounts for ~3% of U.S. cancer diagnoses, and many patients present with locally or regionally advanced disease. Despite multimodal standard-of-care (SOC) treatment, the median overall survival for recurrent or metastatic disease remains ~12 months. Acquired resistance to cisplatin (CDDP) and radiotherapy (RT) remains a central barrier to durable response, motivating neoadjuvant strategies to improve efficacy in resistant tumors. Benzyl isothiocyanate (BITC) is a dietary phytochemical with selective anticancer activity. Across four patient-matched HNSCC cell lines spanning a range of intrinsic sensitivities to CDDP or RT, pretreatment with BITC before RT and CDDP significantly increased HNSCC cell death as measured by caspase-3/7 activity, regardless of each cell line’s single-agent sensitivity. Within 24 h, BITC elevated cytoplasmic ROS across all lines: BITC-resistant cell lines countered this with a more robust increase in the GSH/GSSG ratio and retained viability, whereas the BITC-sensitive lines mounted a weaker glutathione (GSH) response and required rescue with exogenous GSH or N-acetylcysteine (NAC), indicating redox-sensitive cytotoxicity. Transcriptomic time-course analysis suggested that BITC induces a coordinated stress response, including proteotoxic HSF1 activation, and suppresses DNA replication and homologous recombination repair, thereby supporting a transcriptional basis for the observed sensitization to DNA-damaging therapy. By enhancing the efficacy of RT and CDDP in HPV-negative HNSCC, BITC may be a promising neoadjuvant strategy to improve the therapeutic index of chemotherapy and radiation in these patients, warranting further investigation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA",
    "Department of Otolaryngology-Head & Neck Surgery, University of Mississippi Medical Center, Jackson, MS 39216, USA",
    "Department of Radiation Oncology, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA",
    "Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Imani A. Kirven"
    },
    {
      "affs": [
        0
      ],
      "name": "Patrice Penfornis",
      "orcid": "0000-0001-7703-0070"
    },
    {
      "affs": [
        0
      ],
      "name": "Linda L. Eastham"
    },
    {
      "affs": [
        1
      ],
      "name": "Gina D. Jefferson",
      "orcid": "0000-0001-8332-776X"
    },
    {
      "affs": [
        2
      ],
      "name": "Chunli Yang"
    },
    {
      "affs": [
        2
      ],
      "name": "William N. Duggar"
    },
    {
      "affs": [
        2
      ],
      "name": "Rojymon Jacob"
    },
    {
      "affs": [
        3
      ],
      "name": "Lorenzo Lo Muzio",
      "orcid": "0000-0003-4633-4893"
    },
    {
      "affs": [
        0
      ],
      "name": "Pier Paolo Claudio",
      "orcid": "0000-0001-7790-1622"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7qk8t445qyafs.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219990",
  "fulltext_url": null,
  "id": "7qk8t445qyafs",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9990",
  "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": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-07",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/7qk8t445qyafs.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:21:27Z",
      "native_id": "10.3390/ijms27219990",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9990"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Benzyl Isothiocyanate Pretreatment Enhances Chemoradiation Response in HPV-Negative Head and Neck Squamous Cell Carcinoma",
  "title_text": "Benzyl Isothiocyanate Pretreatment Enhances Chemoradiation Response in HPV-Negative Head and Neck Squamous Cell Carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-11-10T00:21:27Z",
  "url": "https://research.draconitic.com/paper/7qk8t445qyafs",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}