{
  "abstract": "Oral squamous cell carcinoma (OSCC) shows aggressive invasion, frequent recurrence, and marked metabolic adaptability. Microbial tryptophan metabolites are increasingly recognized as potential modulators of cancer-related signaling; however, the direct role of indole-3-propionic acid (IPA) in OSCC remains poorly defined. This study examined whether IPA suppresses malignant fitness in HSC-3 and SCC-25 cells while using OKF6/TERT-1, an immortalized human oral keratinocyte cell line, as a non-malignant comparator where biologically appropriate. HSC-3 and SCC-25 cells were treated with vehicle or IPA. Based on the calculated IC50 values from 72 h viability assays, fixed concentrations of 300 µM IPA for HSC-3 cells and 400 µM IPA for SCC-25 cells were selected for subsequent functional experiments. OKF6/TERT-1 cells were used as a non-malignant comparator for baseline transcriptional analyses. Metabolic activity was assessed by the MTS assay. Cytotoxicity and cell death-related stress were additionally examined using lactate dehydrogenase release and colorimetric caspase-3 activity assays. Migration was determined by a wound-healing assay. Metabolic adaptation was evaluated by glucose consumption, lactate secretion, conditioned-medium pH, intracellular adenosine triphosphate, spectrophotometric intracellular reactive oxygen species measurement, and quantitative real-time polymerase chain reaction. Baseline profiling showed that glycolysis-associated transcripts were consistently higher in HSC-3 and SCC-25 cells than in OKF6/TERT-1 cells, with the strongest malignant shift observed in HSC-3. IPA (300 µM for HSC-3, 400 µM for SCC-25) reduced 72 h viability to 55.3% in HSC-3 and 64.8% in SCC-25 cells. IPA increased intracellular reactive oxygen species by 1.86-fold in HSC-3 and 1.49-fold in SCC-25 cells, increased caspase-3 activity, and elevated lactate dehydrogenase release. In parallel, glucose consumption, lactate secretion, adenosine triphosphate content, and migration decreased, whereas conditioned-medium pH and CDH1 expression increased. IPA may directly suppress OSCC cell survival, motility, and glycolytic adaptation while promoting oxidative stress-associated injury and modulating epithelial–mesenchymal transition markers. This metabolic framework may provide a novel experimental direction for OSCC research.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Laboratory Techniques, Vocational School of Health Services, Istanbul Aydin University, 34295 Istanbul, Turkey"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 1,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Negar Taghavi Pourianazar",
      "orcid": "0000-0003-3250-1427"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bg3q3axc4bpk8.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198867",
  "fulltext_url": "https://europepmc.org/articles/PMC13664853",
  "id": "bg3q3axc4bpk8",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/19/8867",
  "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": [
    [
      "openalex",
      "1306|Cancer, Hypoxia, and Metabolism"
    ]
  ],
  "openalex": "W7220464898",
  "pdf_url": "https://europepmc.org/articles/PMC13664853?pdf=render",
  "pmcid": "PMC13664853",
  "pmid": "42884111",
  "published": "2026-10-05",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/bg3q3axc4bpk8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198867",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8867"
    },
    {
      "first_seen": "2026-10-30T12:19:00Z",
      "native_id": "MED:42884111",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42884111"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer, Hypoxia, and Metabolism",
      "subfield": "oncology"
    }
  ],
  "title": "Indole-3-Propionic Acid Disrupts Glycolytic Adaptation and Promotes Oxidative Stress-Associated Injury in Oral Squamous Cell Carcinoma",
  "title_text": "Indole-3-Propionic Acid Disrupts Glycolytic Adaptation and Promotes Oxidative Stress-Associated Injury in Oral Squamous Cell Carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:00Z",
  "url": "https://research.draconitic.com/paper/bg3q3axc4bpk8",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}