{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:09:20Z","timestamp":1788772160576,"version":"build-2803163510"},"reference-count":20,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Agmatine is a naturally occurring polyamine with context-dependent effects on cellular redox regulation, survival, and apoptosis; however, its effects in endometrial cancer cells remain poorly characterized. This exploratory in vitro study investigated cellular responses associated with agmatine sulfate exposure in Ishikawa endometrial adenocarcinoma cells, using human dermal fibroblasts (HDFs) as a non-cancerous, non-tissue-matched comparator. Metabolic activity was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay following exposure to 0.5\u201315 mM agmatine sulfate for 24 and 48 h. Based on the 48-h concentration-response analysis in Ishikawa cells, 4.1 and 6.5 mM were selected for subsequent analyses of intracellular reactive oxygen species (ROS), malondialdehyde (MDA), cleaved caspase-3, and p-AKT\/p-JNK immunoreactivity. Agmatine sulfate produced concentration- and time-dependent reductions in MTT-derived metabolic activity in both cell lines. In Ishikawa cells, 4.1 and 6.5 mM agmatine sulfate significantly increased ROS, MDA, and cleaved caspase-3 levels, accompanied by decreased p-AKT and increased p-JNK immunoreactivity. In HDF cells, ROS levels increased at both concentrations, whereas significant increases in MDA, cleaved caspase-3, and p-JNK were observed only at 6.5 mM; p-AKT immunoreactivity remained unchanged. These findings indicate that agmatine sulfate exposure is associated with reduced metabolic activity, increased oxidative stress and apoptosis-associated responses, and changes in AKT\/JNK-related signalling in Ishikawa cells. However, the responses observed in HDF cells do not support a conclusion of tumour-selective activity. Further studies using additional endometrial cancer cell lines, tissue-matched non-malignant controls, and targeted experimental approaches are warranted to clarify the biological relationships among these responses.<\/jats:p>","DOI":"10.3390\/life16091483","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T08:07:06Z","timestamp":1788768426000},"page":"1483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Agmatine Sulfate Is Associated with Altered Redox Status, Apoptosis-Associated Responses, and AKT\/JNK Signalling in Ishikawa Endometrial Cancer Cells"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2926-6892","authenticated-orcid":false,"given":"Neziha Senem","family":"Ar\u0131","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, K\u00fctahya Health Sciences University, Evliya \u00c7elebi Campus, Tav\u015fanl\u0131 Road 10th km, K\u00fctahya 43100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2466-9417","authenticated-orcid":false,"given":"Ay\u015fe","family":"\u00c7ak\u0131r G\u00fcndo\u011fdu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, K\u00fctahya Health Sciences University, Evliya \u00c7elebi Campus, Tav\u015fanl\u0131 Road 10th km, K\u00fctahya 43100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/S0140-6736(22)00323-3","article-title":"Endometrial cancer","volume":"399","author":"Crosbie","year":"2022","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1158\/1078-0432.CCR-12-0662","article-title":"The PI3K\/AKT\/mTOR pathway as a therapeutic target in endometrial cancer","volume":"18","author":"Slomovitz","year":"2012","journal-title":"Clin. 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