{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:28Z","timestamp":1786977928661,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Accumulating evidence has shown that\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine can, in certain circumstances, suppress tumor development by elevating reactive oxygen species (ROS) levels. The current work set out to examine\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine's apoptotic effects on HuP\u2010T3 cells as well as any potential underlying molecular mechanism(s) that could explain its action as an anticancer agent. In this study, we used 1.2B4 cells as a control human cell line to verify our findings. Hup\u2010T3 and 1.2B4 cells were cultured with a medium containing the following dilutions of\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine: 1\u201310\u2009\u03bc\u039c for up to 72\u2009h. We examined the viability and proliferation levels of cells in both cell lines. Then, we measured only 1.2B4 insulin levels and content. We also quantified cell apoptosis, cell cycle levels, and the intracellular reactive oxygen species on HuP\u2010T3 and 1.2B4. Afterwards, we performed a real\u2010time quantitative polymerase chain reaction and western blot analysis. Our results demonstrated that\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine inhibited both proliferation and growth of Hup\u2010T3 cells, showing inhibitory and antiproliferative activity in comparison with the control group. In addition,\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine had no impact on the proliferation and growth of 1.2B4 cells, nor on their insulin levels and content. By boosting ROS production, and inhibiting the PI3K\/AKT\/mTOR signaling pathway,\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine induced apoptosis on HuP\u2010T3 cells. Pancreatic cancer was successfully inhibited by\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine in vitro.\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine triggers ROS\u2010dependent apoptosis on pancreatic cancer cells while inhibiting the PI3K\/AKT\/mTOR signaling pathway. These findings suggest that\n                    <jats:sc>l<\/jats:sc>\n                    \u2010securinine holds promise as a potential lead for future drug development in the fight against pancreatic adenocarcinoma.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70036","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T14:53:33Z","timestamp":1730127213000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>l<\/scp>\n                    \u2010Securinine Induces ROS\u2010Dependent Apoptosis on Pancreatic Cancer Cells via the PI3K\/AKT\/mTOR Signaling Pathway"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7560-0575","authenticated-orcid":false,"given":"Ioanna A.","family":"Anastasiou","sequence":"first","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital Athens Greece"},{"name":"Department of Pharmacology Medical School, National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Sarantis","sequence":"additional","affiliation":[{"name":"Molecular Oncology Unit, Department of Biological Chemistry Medical School, National and Kapodistrian University of Athens  Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Rebelos","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital Athens Greece"},{"name":"Turku PET Centre University of Turku Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Eleftheriadou","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos N.","family":"Tentolouris","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine Diabetes Center, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital Athens Greece"},{"name":"Department of Pharmacology Medical School, National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasia","family":"Katsaouni","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Medical School, National and Kapodistrian University of Athens Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelos","family":"Koustas","sequence":"additional","affiliation":[{"name":"Molecular Oncology Unit, Department 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