{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:09:35Z","timestamp":1778216975889,"version":"3.51.4"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tongue squamous cell carcinoma (TSCC) is an aggressive malignancy with poor prognosis and limited therapeutic options. Herbal medicines with multitarget activities and low toxicity have attracted increasing attention in cancer adjuvant therapy. This study aimed to investigate the anti-tumor effects and underlying mechanisms of the water extract of Andrographis paniculata (APW) in TSCC in vitro and in vivo. Two TSCC cell lines, Cal-27 and SCC25, were used for cell-based functional and mechanistic studies, while a Cal-27 xenograft-bearing mouse model was established for evaluating the in vivo effect of APW treatment. Our results showed that APW could significantly inhibit the proliferation of Cal-27 and SCC25 cells and induce apoptosis in a concentration-dependent manner. APW could promote mitochondrial-mediated apoptosis by upregulating Bax and cleaved caspase proteins but downregulating Bcl-2 in TSCC cells. It also suppressed the Wnt\/\u03b2-catenin signaling pathway, reducing \u03b2-catenin expression and its downstream targets, CCND1, MYC, and JUN. Furthermore, APW disrupted mitochondrial integrity, induced cytochrome c release, and reduced mitochondrial membrane potential. APW also inhibited epithelial\u2013mesenchymal transition, increasing E-cadherin and decreasing N-cadherin and vimentin expressions, thereby suppressing cell migration of TSCC cells. Furthermore, the 5-week APW treatment significantly reduced tumor growth and angiogenesis without evident hepatic or renal toxicity in Cal-27 xenograft-bearing mice. In conclusion, APW exerted potent anti-tumor effects by targeting both the Wnt\/\u03b2-catenin pathway and mitochondrial apoptotic machinery, suggesting the great potential of APW as an adjuvant therapeutic candidate for TSCC treatment.<\/jats:p>","DOI":"10.3390\/ijms27093772","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T08:08:02Z","timestamp":1777018082000},"page":"3772","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Andrographis paniculata Inhibits Tongue Squamous Cell Carcinoma via Regulating Wnt\/\u03b2-Catenin Signaling and Epithelial-Mesenchymal Transition"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-3566","authenticated-orcid":false,"given":"Grace Gar-Lee","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9163-1251","authenticated-orcid":false,"given":"Jingyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaotong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia Kin-Ming","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9480-4637","authenticated-orcid":false,"given":"Jason Ying Kuen","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7409-1270","authenticated-orcid":false,"given":"Clara Bik-San","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China"},{"name":"School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1601-0825.2000.tb00105.x","article-title":"The epidemiology of tongue cancer: A review of global incidence","volume":"6","author":"Moore","year":"2000","journal-title":"Oral Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.coms.2014.01.001","article-title":"Epidemiologic trends in head and neck cancer and aids in diagnosis","volume":"26","author":"Vigneswaran","year":"2014","journal-title":"Oral Maxillofac. 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