{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:48:54Z","timestamp":1793155734414,"version":"4.5.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005297","name":"Medical University of Bialystok","doi-asserted-by":"publisher","award":["B.SUB.24.415"],"award-info":[{"award-number":["B.SUB.24.415"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometrial cancer (EC) is classified into two main subtypes with distinct molecular profiles. Sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), are crucial regulators of cell survival, apoptosis, and oxidative stress. This study examined the impact of sphingolipid metabolism in Ishikawa (type 1) and HEC-1A (type 2) EC cells following the silencing of Sptlc1 and Sptlc2, which encode subunits of serine palmitoyltransferase (SPT), a key enzyme in de novo sphingolipid synthesis. Gene silencing was confirmed by RT-PCR and Western blot, while sphingolipid levels were quantified using UHPLC\/MS\/MS and the sphingolipid rheostat (S1P\/ceramide ratio) was calculated. Cell viability (MTT assay), cell death, ROS levels (ELISA), total antioxidant capacity (TAC), catalase and caspase-3 activity, and mitochondrial membrane potential were also assessed. The obtained data showed higher ceramide levels in Ishikawa(CON) cells and higher S1P levels in HEC-1A(CON) cells, resulting in a higher sphingolipid rheostat in HEC-1A cells. SPT knockdown reduced sphingolipid levels, increased cell viability, elevated ROS levels, and decreased cell death, particularly in Ishikawa cells. Furthermore, after gene silencing, these cells exhibited reduced catalase activity and diminished TAC, indicating an impaired redox balance. These findings reveal subtype-specific responses to disrupted sphingolipid synthesis and highlight the importance of sphingolipid homeostasis in the behavior of EC cells.<\/jats:p>","DOI":"10.3390\/ijms26104472","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T04:06:21Z","timestamp":1746677181000},"page":"4472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Differential Effects of Sphingolipids on Cell Death and Antioxidant Defenses in Type 1 and Type 2 Endometrial Cancer Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8055-0576","authenticated-orcid":false,"given":"Agnieszka U.","family":"B\u0142achnio-Zabielska","sequence":"first","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrycja","family":"Sadowska","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urszula","family":"Chlabicz","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Pogodzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4618-7838","authenticated-orcid":false,"given":"Herv\u00e9","family":"Le Stunff","sequence":"additional","affiliation":[{"name":"CNRS UMR 9197, Institut des Neurosciences Paris-Saclay, Universit\u00e9 Paris-Saclay, 91400 Saclay, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Lauda\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Gynecological Oncology, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Women\u2019s Health Research Institute, Calisia University, 62-800 Kalisz, Poland"},{"name":"OVIklinika Infertility Center, 01-377 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Szamatowicz","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Ku\u017amicki","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Gynecological Oncology, Medical University of Bialystok, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","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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