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Ion transporters, particularly the sodium\/iodide symporter (SLC5A5), which transport iodine in the form of iodide anion (I\u2212) into cells, have emerged as potential therapeutic targets in tumors of glandular origin. Our research indicates that SLC5A5 is expressed predominantly in ductal cells of human and murine SGC cells. We assessed the effects of potassium iodide (KI), a source of iodide ions. KI treatment reduced SGC cell proliferation and viability without impacting migration. KI increased ROS levels and triggered caspase-dependent apoptosis, as indicated by the upregulation of the pro-apoptotic protein BAX, downregulation of the anti-apoptotic protein Bcl-2, and induction of SGC cell shrinkage. KI did not affect NF-\u03baB or TNF-\u03b1 and SLC5A5 expression. Adding the antioxidant N-acetylcysteine reversed KI-induced growth inhibition, underscoring ROS-induced oxidative stress\u2019s crucial role in growth inhibition. While KI administered in drinking water to mice increased epidermal growth factor (EGF) expression in non-malignant salivary gland tissues, KI decreased EGF receptor (EGFR) expression in malignant SGC cell cultures, where EGFR signaling is frequently dysregulated in SGCs but promoted AKT phosphorylation. Combining KI and anti-EGFR treatment did not yield synergistic anti-SGC cell effects. The study underscores the therapeutic potential of KI as a standalone treatment in vitro for SGC cells. However, the upregulation of EGF in non-malignant tissues and, therefore, the possibility to enhance EGFR-driven signals and AKT phosphorylation after KI treatment in cancer patients could indicate a risk of rendering SGC cells more drug resistant, warranting further investigation to optimize its clinical application.<\/jats:p>","DOI":"10.3390\/ijms26115199","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T10:21:13Z","timestamp":1748427673000},"page":"5199","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Potassium Iodide Induces Apoptosis in Salivary Gland Cancer Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9552-4098","authenticated-orcid":false,"given":"Maksym","family":"Skrypnyk","sequence":"first","affiliation":[{"name":"Juntendo Biomedical Research Core Facilities, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan"},{"name":"Centre for Health Informatics, Australian Institute of Health Innovation, Faculty of Medicine, Health and Human Sciences, Macquarie University, 75 Talavera Road, Sydney, NSW 2109, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8601-1939","authenticated-orcid":false,"given":"Tetiana","family":"Yatsenko","sequence":"additional","affiliation":[{"name":"Juntendo Biomedical Research Core Facilities, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan"},{"name":"Department of Enzymes Chemistry and Biochemistry, Palladin Institute of Biochemistry of NAS of Ukraine, 9 Leontovich Street, 01054 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandra","family":"Riabets","sequence":"additional","affiliation":[{"name":"Juntendo Biomedical Research Core Facilities, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan"},{"name":"Department of Neurosurgery, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Zuieva","sequence":"additional","affiliation":[{"name":"Juntendo Biomedical Research Core Facilities, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iryna","family":"Rodionova","sequence":"additional","affiliation":[{"name":"Juntendo Biomedical Research Core Facilities, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan"},{"name":"Center for Genome and Regenerative Medicine, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-2703","authenticated-orcid":false,"given":"Margarita","family":"Skikevych","sequence":"additional","affiliation":[{"name":"Department of Surgical Dentistry and Maxillofacial Surgery with Plastic and Reconstructive Surgery of Head and Neck, Poltava State Medical University, 23 Shevchenko Street, 36011 Poltava, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6254-6381","authenticated-orcid":false,"given":"Yousef","family":"Salama","sequence":"additional","affiliation":[{"name":"An-Najah Center for Cancer and Stem Cell Research, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. 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