{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T06:03:41Z","timestamp":1784527421707,"version":"3.55.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The telomerase catalytic subunit hTERT is a critical oncogenic driver in nasopharyngeal carcinoma (NPC). The specific role of aloe-emodin (AE) in regulating hTERT in NPC has not been systematically investigated. The regulatory network involving hTERT and its upstream transcription factors, c-Myc and E2F1, offers a promising therapeutic avenue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Bioinformatics was used to analyze hTERT expression and its prognostic significance in head and neck squamous cell carcinoma and nasopharyngeal carcinoma. Molecular docking simulations were conducted to investigate the potential interaction between AE and hTERT. hTERT expression was assessed in normal nasal epithelial cells and NPC cell lines. Effects of AE on hTERT, c-Myc, and E2F1 were measured using qRT-PCR and Western blotting. Telomerase activity was evaluated through TRAP-qPCR and PAGE. hTERT was knocked down using siRNA. Cell proliferation, migration, and invasion were analyzed using CCK-8, EdU, colony formation, and Transwell assays. ROS levels were quantified using DCFH-DA staining.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , a subcutaneous xenograft model was established to assess AE\u2019s anti-tumor efficacy alone and with shRNA-mediated hTERT knockdown. Organ toxicity was evaluated by H&amp;amp;E staining. Tumor tissues were analyzed by immunohistochemistry for hTERT, c-Myc, E2F1, Ki-67, and Cleaved Caspase-3.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Bioinformatics analysis revealed elevated hTERT expression in HNSC tissues and NPC cell lines Molecular docking predicted a potential interaction between AE and the catalytic pocket of hTERT.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , AE treatment decreased c-Myc, increased E2F1, and reduced hTERT transcription. AE also reduced telomerase activity, increased ROS levels, and suppressed proliferation, migration, and invasion in NPC cells.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , AE showed anti-tumor activity. Combined with hTERT knockdown, AE produced synergistic tumor suppression and enhanced modulation of the c-Myc\/E2F1\/hTERT axis and oxidative stress. Immunohistochemistry revealed suppressed proliferation and increased apoptosis in tumor tissues of the combination group. No significant organ toxicity was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study presents the first systematic validation of AE\u2019s anti-NPC effects. These include hTERT suppression, modulation of the c-Myc\/E2F1 network, and induction of oxidative stress. These findings suggest a potential therapeutic target and strategy for NPC. The results support the clinical translation of AE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1850685","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:35:10Z","timestamp":1784525710000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Aloe-emodin inhibits nasopharyngeal carcinoma by modulating telomerase activity involving the c-Myc\/E2F1 axis"],"prefix":"10.3389","volume":"17","author":[{"given":"Mengqin","family":"Li","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"College of Pharmacy, Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhong","family":"Li","sequence":"additional","affiliation":[{"name":"Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zeng","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"College of Pharmacy, Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahua","family":"Hu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Su","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Huang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhong","family":"Tang","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"Guangxi Health Commission Key Laboratory of Glucose and Lipid Metabolism Disorders, The Second Affiliated Hospital of Guilin Medical University","place":["Guilin, Guangxi, China"]},{"name":"School of General Medicine, Guilin Medical University","place":["Guilin, Guangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"zqac043","DOI":"10.1093\/function\/zqac043","article-title":"Noncanonical role of telomerase in regulation of microvascular redox environment with implications for coronary artery disease","volume":"3","author":"Ait-Aissa","year":"2022","journal-title":"Funct. (Oxf)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1038\/s41467-026-68560-8","article-title":"Structures of nucleotide-bound human telomerase at several steps of its telomeric DNA repeat addition cycle","volume":"17","author":"Balch","year":"2026","journal-title":"Nat. Commun."},{"key":"B3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/s0140-6736(21)01123-5","article-title":"Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial","volume":"398","author":"Chen","year":"2021","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41419-022-04783-z","article-title":"Identification of a novel mechanism for reversal of doxorubicin-induced chemotherapy resistance by TXNIP in triple-negative breast cancer via promoting reactive oxygen-mediated DNA damage","volume":"13","author":"Chen","year":"2022","journal-title":"Cell Death Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2979","DOI":"10.1002\/ptr.7793","article-title":"Aloe-emodin targets multiple signaling pathways by blocking ubiquitin-mediated degradation of DUSP1 in nasopharyngeal carcinoma cells","volume":"37","author":"Chen","year":"2023","journal-title":"Phytother. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1093\/nar\/29.13.2789","article-title":"E2F-1 represses transcription of the human telomerase reverse transcriptase gene","volume":"29","author":"Crowe","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.ejmech.2018.09.020","article-title":"Designing anticancer copper(II) complexes by optimizing 2-pyridine-thiosemicarbazone ligands","volume":"158","author":"Deng","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"102169","DOI":"10.1016\/j.labinv.2024.102169","article-title":"Leptin modulates ovarian granulosa cell apoptosis by regulating telomerase activity and telomere length in polycystic ovary syndrome","volume":"105","author":"Feijing","year":"2025","journal-title":"Lab. Invest"},{"key":"B9","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1186\/s12885-017-3471-6","article-title":"Joint quantitative measurement of hTERT mRNA in both peripheral blood and circulating tumor cells of patients with nasopharyngeal carcinoma and its clinical significance","volume":"17","author":"Fu","year":"2017","journal-title":"BMC Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1573408","DOI":"10.3389\/fphar.2025.1573408","article-title":"Aloe-emodin mediates the inhibitory effect of LncRNA D63785 on the PI3K\/Akt\/mTOR pathway in nasopharyngeal carcinoma","volume":"16","author":"He","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"129113","DOI":"10.1016\/j.talanta.2025.129113","article-title":"Noninvasive nasopharyngeal cancer screening via salivary DNA detection using label-free surface-enhanced raman spectroscopy","volume":"299","author":"Hou","year":"2026","journal-title":"Talanta"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1016\/j.ijrobp.2025.06.3870","article-title":"Global disparities in current clinical trials in nasopharyngeal carcinoma","volume":"123","author":"Jainar","year":"2025","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"B13","doi-asserted-by":"publisher","first-page":"130151","DOI":"10.1016\/j.ijbiomac.2024.130151","article-title":"Telomerase inhibitors induce mitochondrial oxidation and DNA damage-dependent cell death rescued by Bcl-2\/Bcl-xL","volume":"264","author":"Jayaprasad","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/s12935-021-01942-8","article-title":"Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells","volume":"21","author":"Jiang","year":"2021","journal-title":"Cancer Cell Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"D1670","DOI":"10.1093\/nar\/gkae973","article-title":"Generic diagramming platform (GDP): a comprehensive database of high-quality biomedical graphics","volume":"53","author":"Jiang","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.3390\/cells13221823","article-title":"Axl and EGFR dual-specific binding affibody for targeted therapy in nasopharyngeal carcinoma","volume":"13","author":"Kamara","year":"2024","journal-title":"Cells"},{"key":"B17","doi-asserted-by":"publisher","first-page":"4473","DOI":"10.1002\/ptr.7913","article-title":"Apoptotic and anti-warburg effect of morusin via ROS mediated inhibition of FOXM1\/c-Myc signaling in prostate cancer cells","volume":"37","author":"Koo","year":"2023","journal-title":"Phytother. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41419-024-06454-7","article-title":"The regulations of telomerase reverse transcriptase (TERT) in cancer","volume":"15","author":"Liu","year":"2024","journal-title":"Cell Death Dis."},{"key":"B19","doi-asserted-by":"publisher","first-page":"109757","DOI":"10.1016\/j.celrep.2021.109757","article-title":"HIF-1 recruits NANOG as a coactivator for TERT gene transcription in hypoxic breast cancer stem cells","volume":"36","author":"Lu","year":"2021","journal-title":"Cell Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.3390\/ijms20081823","article-title":"Telomerase-targeted cancer immunotherapy","volume":"20","author":"Mizukoshi","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"189265","DOI":"10.1016\/j.bbcan.2025.189265","article-title":"Programmed cell death in nasopharyngeal carcinoma: mechanisms and therapeutic targets","volume":"1880","author":"Qian","year":"2025","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"B22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.ejmech.2016.08.054","article-title":"Stabilization of c-myc G-Quadruplex DNA, inhibition of telomerase activity, disruption of mitochondrial functions and tumor cell apoptosis by platinum(II) complex with 9-amino-oxoisoaporphine","volume":"124","author":"Qin","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/s41580-020-0234-z","article-title":"Regulation of human telomerase in homeostasis and disease","volume":"21","author":"Roake","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1016\/j.drudis.2019.05.015","article-title":"Raising the bar in anticancer therapy: recent advances in, and perspectives on, telomerase inhibitors","volume":"24","author":"Saraswati","year":"2019","journal-title":"Drug Discov. Today"},{"key":"B25","doi-asserted-by":"publisher","first-page":"7928200","DOI":"10.1155\/2022\/7928200","article-title":"Advances in understanding the role of aloe emodin and targeted drug delivery systems in cancer","volume":"2022","author":"\u015eeker Karatoprak","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"173550","DOI":"10.1016\/j.ejphar.2020.173550","article-title":"Aloe-emodin induces autophagy and apoptotic cell death in non-small cell lung cancer cells via Akt\/mTOR and MAPK signaling","volume":"886","author":"Shen","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1007\/s43440-020-00062-w","article-title":"Aloe emodin inhibits telomerase activity in breast cancer cells: transcriptional and enzymological mechanism","volume":"72","author":"Wang","year":"2020","journal-title":"Pharmacol. Rep."},{"key":"B28","doi-asserted-by":"publisher","first-page":"11328","DOI":"10.1073\/pnas.0401801101","article-title":"Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells","volume":"101","author":"Won","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B29","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/s41419-018-0498-9","article-title":"c-MYC and reactive oxygen species play roles in tetrandrine-induced leukemia differentiation","volume":"9","author":"Wu","year":"2018","journal-title":"Cell Death Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/s41698-020-00140-5","article-title":"Synergistic activation of mutant TERT promoter by Sp1 and GABPA in BRAF(V600E)-driven human cancers","volume":"5","author":"Wu","year":"2021","journal-title":"NPJ Precis. Oncol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"pgad046","DOI":"10.1093\/pnasnexus\/pgad046","article-title":"Transcriptional analysis links B cells and TERT expression to favorable prognosis in head and neck cancer","volume":"2","author":"Xian","year":"2023","journal-title":"PNAS Nexus"},{"key":"B32","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1186\/s12935-021-02217-y","article-title":"Dynamic serum biomarkers to predict the efficacy of PD-1 in patients with nasopharyngeal carcinoma","volume":"21","author":"Zhang","year":"2021","journal-title":"Cancer Cell Int."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1007\/s00259-022-05684-1","article-title":"Targeting visualization of malignant tumor based on the alteration of DWI signal generated by hTERT promoter-driven AQP1 overexpression","volume":"49","author":"Zhang","year":"2022","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1850685\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T05:35:12Z","timestamp":1784525712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1850685\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":33,"alternative-id":["10.3389\/fphar.2026.1850685"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1850685","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"article-number":"1850685"}}