{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:56:14Z","timestamp":1791204974824,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>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 \u00b5M IPA for HSC-3 cells and 400 \u00b5M 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 \u00b5M for HSC-3, 400 \u00b5M 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\u2013mesenchymal transition markers. This metabolic framework may provide a novel experimental direction for OSCC research.<\/jats:p>","DOI":"10.3390\/ijms27198867","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:31:31Z","timestamp":1791203491000},"page":"8867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Indole-3-Propionic Acid Disrupts Glycolytic Adaptation and Promotes Oxidative Stress-Associated Injury in Oral Squamous Cell Carcinoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3250-1427","authenticated-orcid":false,"given":"Negar","family":"Taghavi Pourianazar","sequence":"first","affiliation":[{"name":"Medical Laboratory Techniques, Vocational School of Health Services, Istanbul Aydin University, 34295 Istanbul, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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