{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:53:03Z","timestamp":1767747183961,"version":"3.48.0"},"reference-count":16,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["NSTC113\u20102320\u2010B\u2010041\u2010001\u2010MY3"],"award-info":[{"award-number":["NSTC113\u20102320\u2010B\u2010041\u2010001\u2010MY3"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["NSTC113\u20102314\u2010B\u2010037\u2010034"],"award-info":[{"award-number":["NSTC113\u20102314\u2010B\u2010037\u2010034"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      16\u2010hydroxycleroda\u20103,13\u2010dien\u201015,16\u2010olide (HCD), a compound isolated from\n                      <jats:italic>Polyalthia longifolia<\/jats:italic>\n                      var.\n                      <jats:italic>pendula<\/jats:italic>\n                      , has been identified as a PI3K inhibitor.\n                      <jats:italic>\n                        <jats:styled-content style=\"fixed-case\">P. longifolia<\/jats:styled-content>\n                        var. pendula\n                      <\/jats:italic>\n                      is recognized for its diverse pharmacological properties, including antimicrobial, hypotensive, anti\u2010inflammatory, and cytotoxic activities. Considering the pivotal role of PI3K in the regulation of apoptosis in cancer cells, this study aims to investigate the apoptotic effects induced by HCD in head and neck cancer cell models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The study focused on investigating the mechanism through which HCD induces apoptosis in oral squamous cell carcinoma (OSCC) using SCC25 and SCC180 cells. These cells were treated with HCD at IC\n                      <jats:sub>20<\/jats:sub>\n                      , IC\n                      <jats:sub>50<\/jats:sub>\n                      , and IC\n                      <jats:sub>80<\/jats:sub>\n                      concentrations over periods of 24, 48, and 72\u2009h. Assessments included cell viability, oxidative stress levels using MitoSOX and CellROX, and the analysis of gene and protein expressions related to apoptosis via immunofluorescence staining, flow cytometry, RT\u2010PCR, and western blotting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results demonstrated that HCD significantly increased the sub\u2010G\n                      <jats:sub>1<\/jats:sub>\n                      phase cell population, suppressed clonogenic activity, and promoted mitochondrial ROS production, accompanied by a reduction in glutathione levels. HCD also activated cytochrome\n                      <jats:italic>c<\/jats:italic>\n                      (cyto.\n                      <jats:italic>c<\/jats:italic>\n                      ) release and Bax expression while downregulating Bcl\u20102 expression. Notably, in SCC25 cells, HCD induced apoptosis through the TNF\u2010\u03b1\/TNF\u2010R and FasL\/Fas death domains, leading to caspase cascade activation. Moreover, HCD showed dose\u2010dependent growth inhibition of SCC25 cells, both alone and combined with cisplatin, by enhancing caspase\u20103 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This investigation into HCD's molecular mechanisms in OSCC cells offers insight into developing effective anticancer therapies, highlighting its role in apoptosis induction through oxidative stress, mitochondrial pathways, and death receptor signaling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jop.70060","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T23:10:23Z","timestamp":1757977823000},"page":"61-72","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <scp>PI3K<\/scp>\n                    Inhibitor\n                    <scp>HCD<\/scp>\n                    Promotes Caspase Activation in Head and Neck Squamous Cells by Upregulating the Extrinsic and Intrinsic Apoptosis Pathways"],"prefix":"10.1111","volume":"55","author":[{"given":"Leong\u2010Perng","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya\u2010Ping","family":"Tseng","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences National Cheng Kung University  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Ching","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology and Oncology Kaohsiung Medical University Hospital, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen\u2010Yu","family":"Chien","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University  Kaohsiung Taiwan"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Kaohsiung Municipal Siaogang Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1052-5348","authenticated-orcid":false,"given":"Che\u2010Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling\u2010Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2010Head and Neck Surgery Kaohsiung Medical University Hospital, Faculty of Medicine, College of Medicine, Kaohsiung Medical University  Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tung\u2010Wen","family":"Yen","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Science and Institute of Cosmetic Science Chia nan University of Pharmacy and Science  Tainan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Po\u2010Chun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Food and Drug Industry and Inspective Technology Chia nan University of Pharmacy and Science  Tainan 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