{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:59:38Z","timestamp":1791197978051,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Funds of Joint Research Center for Food Nutrition and Health of IHM","award":["2023SJY02"],"award-info":[{"award-number":["2023SJY02"]}]},{"name":"the Fund of Green Food Deep Processing and Resource Utilization Research Innovation Team","award":["2025KYTD17"],"award-info":[{"award-number":["2025KYTD17"]}]},{"name":"2025 Anhui Provincial Program for Science and Engineering University Teachers\u2019 Temporary Practice in Enterprises","award":["2025jsqygz51"],"award-info":[{"award-number":["2025jsqygz51"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Silver nanoparticles (AgNPs) have emerged as a promising nanoplatform for oncological intervention, yet their clinical translation is severely hampered by systemic toxicities associated with high effective doses, while the underlying mechanisms governing their interactions with cancer cell pro-survival cascades remain poorly defined. In this study, we synthesized and fully characterized green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG)-derived silver nanoparticles (EAgNPs), in which EGCG acts as the reducing and capping agent. EAgNPs were confirmed to be highly dispersed, stable metallic silver particles with a primary size range of 4\u20137.6 nm. Subsequent mechanistic investigations performed on Tca8113 human tongue cancer cells revealed distinct dose-dependent anticancer action modes of EAgNPs: the 100 \u03bcM lethal dose effectively triggered robust apoptosis via potently suppressing the activity of key antioxidant selenoenzymes, including thioredoxin reductase and glutathione peroxidase (GPx), and multiple drug resistance proteins. Notably, even under this lethal treatment condition, Tca8113 cells still initiated theNrf2-associated antioxidant response characterized by 2-fold glutathione elevation and 25-fold heme oxygenase-1 upregulation. The 30 \u03bcM low-dose EAgNPs, however, failed to produce salient cytotoxicity, as they moderately inhibited GPx activity while comprehensively activating the integrated cancer cell defense network, including glutathione accumulation, Nrf2-associated antioxidant protein induction, and upregulation of a full panel of drug resistance proteins. Interestingly, the combination of 30 \u03bcM EAgNPs with the glutathione synthesis inhibitor L-buthionine-sulfoximine further enhanced selenoenzyme GPx inhibition and completely abrogated all above-mentioned inducible anti-apoptotic responses, resulting in multi-target disruption of the cytoprotective system and strongly enhanced apoptosis induction. Our findings demonstrate that this combinatorial strategy effectively lowers the therapeutic dose threshold of EAgNPs by disabling cancer cell adaptive resistance, providing a low-toxicity, translationally feasible approach for localized oral cancer treatment.<\/jats:p>","DOI":"10.3390\/molecules31193536","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:02:27Z","timestamp":1791194547000},"page":"3536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Responses of Anti-Apoptotic Molecules to EAgNPs and EAgNPs Plus L-Buthionine-Sulfoximine in Human Tongue Cancer Cells"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-952X","authenticated-orcid":false,"given":"Ximing","family":"Wu","sequence":"first","affiliation":[{"name":"Anhui Province Green Food Collaborative Technology Service Center for Rural Revitalization, School of Biological and Food Engineering, Hefei Normal University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Fuming","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Anhui Agricultural University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Xiaoyu","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Anhui Agricultural University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Mingchuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Medical Devices, Shandong Drug and Food Vocational College, Weihai 264210, China"},{"name":"Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Yufeng","family":"He","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Anhui Agricultural University, Hefei 230601, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-9819","authenticated-orcid":false,"given":"Jinsong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Institute of Health and Medicine, Hefei Comprehensive National Science Center, Anhui Agricultural University, Hefei 230601, China"},{"name":"Department of Medical Devices, Shandong Drug and Food Vocational College, Weihai 264210, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Huali","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Devices, Shandong Drug and Food Vocational College, Weihai 264210, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115532","DOI":"10.1016\/j.biopha.2023.115532","article-title":"Antitumor effect of algae silver nanoparticles on human triple negative breast cancer cells","volume":"168","author":"Salih","year":"2023","journal-title":"Biomed. 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