{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:55:29Z","timestamp":1790564129114,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102024\u201000413760"],"award-info":[{"award-number":["RS\u20102024\u201000413760"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gliomas remain among the most lethal brain tumours, driven by aggressive invasion, stem\u2010like properties, metabolic plasticity, and frequent resistance to temozolomide (TMZ). Hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) is a central regulator of these malignant traits. In this study, we identify methyl 4\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010demethylbarbatate (Me\u20104\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010DBA), a biosynthetically produced lichen\u2010derived metabolite, as a potential modulator of HIF\u20101\u03b1 signaling. Molecular docking analysis suggested a possible interaction between Me\u20104\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010DBA and HIF\u20101\u03b1 near the Lys304 ubiquitination site, which may contribute to reduced HIF\u20101\u03b1 stability and suppression of downstream EMT and stemness signaling. This inhibition simultaneously attenuated both glycolytic activity and mitochondrial respiration, indicating a broad suppression of metabolic reprogramming. Network pharmacology and molecular docking further indicated HIF\u20101\u03b1\u2010associated signaling as a potential regulatory hub, while in\u00a0vitro assays demonstrated marked reductions in glioma cell viability, invasion, migration, and clonogenicity. Notably, Me\u20104\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010DBA synergised with TMZ to enhance suppression of motility, stemness, and metabolic activity, resulting in profound impairment of tumourigenic potential. In\u00a0vivo zebrafish assays also indicated a favourable safety profile at the tested concentrations. Together, these findings suggest that Me\u20104\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010DBA suppresses HIF\u20101\u03b1\u2010associated malignant phenotypes and enhances TMZ responsiveness in glioma cells, highlighting its potential as a natural product\u2010derived modulator of glioma progression.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70279","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:19:01Z","timestamp":1790561941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methyl 4\u2010\n                    <i>O<\/i>\n                    \u2010Demethylbarbatate Destabilises\n                    <scp>HIF<\/scp>\n                    \u20101\u03b1 and Enhances Temozolomide Sensitivity in Glioma Cells"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3785-0159","authenticated-orcid":false,"given":"Rui","family":"Zhou","sequence":"first","affiliation":[{"name":"College of Pharmacy, Sunchon National University  Sunchon Jeollanam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6175-4015","authenticated-orcid":false,"given":"M\u00fccahit","family":"Varl\u0131","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Sunchon National University  Sunchon Jeollanam\u2010do Republic of Korea"},{"name":"Department of Microbiology, Tumor and Cell Biology Karolinska Institute  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rundong","family":"Liu","sequence":"additional","affiliation":[{"name":"Korea Lichen Research Institute Sunchon National University  Sunchon Republic of Korea"},{"name":"Ningbo Institute of Marine Medicine Peking University  Ningbo China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung\u2010Ho","family":"Ha","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Sunchon National University  Sunchon Jeollanam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae\u2010Seoun","family":"Hur","sequence":"additional","affiliation":[{"name":"Korea Lichen Research Institute Sunchon National University  Sunchon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5769-0792","authenticated-orcid":false,"given":"Sang Kyum","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Chungnam National University  Daejeon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hahyun","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Sunchon National University  Sunchon Jeollanam\u2010do Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5889-8907","authenticated-orcid":false,"given":"Hangun","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Sunchon National University  Sunchon Jeollanam\u2010do Republic of 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