Responses of Anti-Apoptotic Molecules to EAgNPs and EAgNPs Plus L-Buthionine-Sulfoximine in Human Tongue Cancer Cells
4 affiliations
- 1Anhui Province Green Food Collaborative Technology Service Center for Rural Revitalization, School of Biological and Food Engineering, Hefei Normal University, Hefei 230601, China
- 2State 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
- 3Department of Medical Devices, Shandong Drug and Food Vocational College, Weihai 264210, China
- 4Tea Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310008, China
Abstract
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 4–7.6 nm. Subsequent mechanistic investigations performed on Tca8113 human tongue cancer cells revealed distinct dose-dependent anticancer action modes of EAgNPs: the 100 μM 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 μM 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 μM 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.
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BibTeX
@article{wu2026responses,
title = {{Responses of Anti-Apoptotic Molecules to EAgNPs and EAgNPs Plus L-Buthionine-Sulfoximine in Human Tongue Cancer Cells}},
author = {Ximing Wu and Fuming Wang and Xiaoyu Huang and Mingchuan Yang and Yufeng He and Jinsong Zhang and Huali Wang},
journal = {Molecules (Basel, Switzerland)},
year = {2026},
month = oct,
doi = {10.3390/molecules31193536},
url = {https://europepmc.org/article/PMC/PMC13667187},
note = {CC BY},
}
RIS
TY - JOUR
TI - Responses of Anti-Apoptotic Molecules to EAgNPs and EAgNPs Plus L-Buthionine-Sulfoximine in Human Tongue Cancer Cells
AU - Ximing Wu
AU - Fuming Wang
AU - Xiaoyu Huang
AU - Mingchuan Yang
AU - Yufeng He
AU - Jinsong Zhang
AU - Huali Wang
PY - 2026
DA - 2026/10/01
JO - Molecules (Basel, Switzerland)
DO - 10.3390/molecules31193536
UR - https://europepmc.org/article/PMC/PMC13667187
AB - 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 4–7.6 nm. Subsequent mechanistic investigations performed on Tca8113 human tongue cancer cells revealed distinct dose-dependent anticancer action modes of EAgNPs: the 100 μM 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 μM 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 μM 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.
SN - 1420-3049
ER -