{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:43Z","timestamp":1787028583168,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to compare the responses of normal human gingival epithelial cells (HGEpiC) and oral squamous cell carcinoma cells (OECM-1) to apigenin, a natural flavonoid, focusing on redox balance, autophagy, and apoptosis. This study is among the first to directly compare apigenin-induced responses in normal and cancerous oral epithelial cells. Cells were exposed to apigenin for 24 or 48 h, with untreated cells as controls. Mitochondrial activity, ATP, ROS (H2O2), and GSH were measured. Proliferation and morphology were monitored using HoloMonitor\u00ae M4. Autophagy was assessed by fluorescent vacuole labeling, and apoptosis-related proteins (p-AKT, p-BCL-2, p-p53, p-JNK, caspase-8\/9) by Luminex assay. Late apoptosis was evaluated by caspase-3\/7 activity. Apigenin elicited a differential response: in HGEpiC cells, it was non-cytotoxic and increased metabolic activity, induced a moderate ROS increase, and activated autophagy as a pro-survival mechanism; in contrast, OECM-1 cells exhibited a significant reduction in metabolic activity, a marked ATP decrease at 24 h, and a pronounced ROS increase. These alterations were associated with reduced autophagy and decreased p-JNK signaling. These findings indicate that apigenin exerted no harmful effects on HGEpiC cells, while inducing redox imbalance in OECM-1 cells, highlighting a context-dependent cellular response.<\/jats:p>","DOI":"10.3390\/ijms27052091","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:14:44Z","timestamp":1771928084000},"page":"2091","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential Effects of Apigenin on Normal and Squamous Oral Epithelial Cells Reveal Redox\u2013Autophagy Signaling Vulnerabilities in OSCC"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7073-3309","authenticated-orcid":false,"given":"Bianca","family":"Voicu Balasea","sequence":"first","affiliation":[{"name":"The Interdisciplinary Center for Dental Research and Development, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 19-21 Jean Louis Calderon, 030167 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6273-8540","authenticated-orcid":false,"given":"Miruna-Silvia","family":"Stan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 91\u201395 Splaiul Independentei, 050095 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1872-9956","authenticated-orcid":false,"given":"Miruna","family":"Dinescu","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Faculty of Dentistry, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, District 2, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Imre","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Faculty of Dentistry, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 37 Dionisie Lupu Street, District 2, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radu","family":"Radulescu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 17-23 Plevnei Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6970-1307","authenticated-orcid":false,"given":"Ana","family":"Cernega","sequence":"additional","affiliation":[{"name":"Department of Organization, Professional Legislation and Management of the Dental Office, Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 17-23 Plevnei Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1753-3765","authenticated-orcid":false,"given":"Monica","family":"Musteanu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Complutense of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4345-282X","authenticated-orcid":false,"given":"Alexandra","family":"Ripszky","sequence":"additional","affiliation":[{"name":"The Interdisciplinary Center for Dental Research and Development, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 19-21 Jean Louis Calderon, 030167 Bucharest, Romania"},{"name":"Department of Biochemistry, Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 17-23 Plevnei Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6766-7772","authenticated-orcid":false,"given":"Silviu Mirel","family":"Pituru","sequence":"additional","affiliation":[{"name":"The Interdisciplinary Center for Dental Research and Development, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 19-21 Jean Louis Calderon, 030167 Bucharest, Romania"},{"name":"Department of Organization, Professional Legislation and Management of the Dental Office, Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 17-23 Plevnei Street, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S204","DOI":"10.4103\/jpbs.jpbs_593_25","article-title":"A Narrative Review on Oral Squamous Cell Carcinoma","volume":"17","author":"Muralidharan","year":"2025","journal-title":"J. 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