{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:50:55Z","timestamp":1781844655116,"version":"3.54.5"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460954"],"award-info":[{"award-number":["82460954"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Tongue squamous cell carcinoma (TSCC) often develops therapeutic resistance. Metabolic reprogramming, particularly the glycolysis\/lactate\/histone lactylation axis, is a critical driver of tumor progression and therapy resistance. This study investigated the anti\u2010tumor mechanism of Rhaponticin (Rha), focusing on the metabolic\/epigenetic axis involving hypoxia\u2010inducible factor 1\u03b1 (HIF\u20101\u03b1), glycolysis, and histone H3K18 lactylation (H3K18la). SCC9 and SCC9\u2010CisR cells were treated with Rha alone or in combination with 2\u2010deoxy\u2010D\u2010glucose (2\u2010DG) or sodium lactate (LacNa). The effects of Rha on glycolysis and H3K18la were evaluated by extracellular acidification rate assays, glucose\/lactate quantification, and western blotting. Gain\u2010 and loss\u2010of\u2010function studies targeting HIF\u20101\u03b1 were conducted to determine the mechanistic dependency of Rha\u2010mediated effects. Subcutaneous and liver metastasis xenograft models were established for in\u00a0vivo validation. Rha significantly suppressed glycolysis, glucose consumption, and lactate production, concomitant with the downregulation of HK2, LDHA, GLUT1, and H3K18la levels. Rha not only mimicked the effects of 2\u2010DG by inhibiting clonogenicity, migration, and invasion and decreasing cisplatin resistance in SCC9 or SCC9\u2010CisR cells but also reversed LacNa\u2010mediated promotion of these parameters, indicating that Rha acts through the glycolysis\/lactate pathway. Rha inhibited tumor growth and liver metastasis, enhanced cisplatin sensitivity, and decreased H3K18la levels in mouse models. Mechanistically, Rha inhibited HIF\u20101\u03b1, thereby attenuating glycolytic flux and decreasing lactate\u2010driven H3K18la. Rha inhibits TSCC progression and enhances cisplatin sensitivity by targeting HIF\u20101\u03b1 and repressing the glycolysis\/lactate\/H3K18la axis, suggesting that Rha is a promising candidate for disrupting metabolic\/epigenetic crosstalk in TSCC.<\/jats:p>","DOI":"10.1002\/kjm2.70254","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T03:58:37Z","timestamp":1781841517000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rhaponticin Blocks Glycolysis\u2010Mediated Histone Lactylation to Suppress Tongue Squamous Cell Carcinoma via\n                    <scp>HIF<\/scp>\n                    \u20101\u03b1 Activity Inhibition"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6520-9521","authenticated-orcid":false,"given":"Yuan","family":"Wu","sequence":"first","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang\u2010Liang","family":"Yao","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"},{"name":"Internal Medicine of Traditional Chinese Medicine Affiliated Hospital of Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yi","family":"Fang","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Sen","family":"Shao","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"},{"name":"Department of Oral and Maxillofacial Surgery Affiliated Hospital of Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8136-3186","authenticated-orcid":false,"given":"Xiao\u2010Wen","family":"Wan","sequence":"additional","affiliation":[{"name":"Jiangxi University of Chinese Medicine  Nanchang Jiangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"issue":"2","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/odi.13897","article-title":"Epidemiology of Tongue Squamous Cell Carcinoma: A Retrospective Cohort Study","volume":"29","author":"Silva Souto A. 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Cell Physiology"},{"issue":"3","key":"e_1_2_8_6_1","doi-asserted-by":"crossref","first-page":"157","DOI":"10.35772\/ghm.2020.01084","article-title":"Surgical Treatment for Oral Tongue Squamous Cell Carcinoma: A Retrospective Study of 432 Patients","volume":"3","author":"Oikawa Y.","year":"2021","journal-title":"Global Health & Medicine"},{"issue":"20","key":"e_1_2_8_7_1","doi-asserted-by":"crossref","first-page":"5739","DOI":"10.7150\/thno.37556","article-title":"Decreased Expression of Mitochondrial miR\u20105787 Contributes to Chemoresistance by Reprogramming Glucose Metabolism and Inhibiting MT\u2010CO3 Translation","volume":"9","author":"Chen W.","year":"2019","journal-title":"Theranostics"},{"issue":"6","key":"e_1_2_8_8_1","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.4149\/neo_2020_191119N1187","article-title":"Long Noncoding RNA UCA1 Regulates CCR7 Expression to Promote Tongue Squamous Cell Carcinoma Progression by Sponging miR\u2010138\u20105p","volume":"67","author":"Shi T. 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