{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:11Z","timestamp":1789632191828,"version":"build-2803163510"},"reference-count":52,"publisher":"Spandidos Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oncol Lett"],"DOI":"10.3892\/ol.2026.15818","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:27:22Z","timestamp":1786706842000},"page":"1-12","source":"Crossref","is-referenced-by-count":0,"title":["Flavokawain A inhibits high glucose\u2011induced malignant progression of lung cancer cells by suppressing\u00a0PRMT5\u2011mediated PTEN neddylation and nuclear translocation"],"prefix":"10.3892","volume":"32","author":[{"given":"Lei","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250013, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong 250033, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250013, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250013, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250013, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyao","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250013, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2249","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"key20260917101257_b1-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.ccell.2023.12.021","article-title":"Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer","volume":"42","author":"Cords","year":"2024","journal-title":"Cancer Cell"},{"key":"key20260917101257_b2-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.jtho.2024.08.016","article-title":"MUC1-C is a common driver of acquired osimertinib resistance in NSCLC","volume":"19","author":"Haratake","year":"2024","journal-title":"J Thorac Oncol"},{"key":"key20260917101257_b3-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1016\/S0140-6736(24)01029-8","article-title":"New promises and challenges in the treatment of advanced non-small-cell lung cancer","volume":"404","author":"Meyer","year":"2024","journal-title":"Lancet"},{"key":"key20260917101257_b4-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1080\/14737140.2024.2362889","article-title":"First-line concomitant EGFR-TKI + chemotherapy versus EGFR-TKI alone for advanced EGFR-mutated NSCLC: A meta-analysis of randomized phase III trials","volume":"24","author":"Landre","year":"2024","journal-title":"Expert Rev Anticancer Ther"},{"key":"key20260917101257_b5-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1158\/2159-8290.CD-20-1211","article-title":"Metabolic codependencies in the tumor microenvironment","volume":"11","author":"Dey","year":"2021","journal-title":"Cancer Discov"},{"key":"key20260917101257_b6-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1353787","DOI":"10.3389\/fimmu.2024.1353787","article-title":"Involvement of tumor immune microenvironment metabolic reprogramming in colorectal cancer progression, immune escape, and response to immunotherapy","volume":"15","author":"Nicolini","year":"2024","journal-title":"Front Immunol"},{"key":"key20260917101257_b7-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1158\/2159-8290.CD-23-1319","article-title":"High glucose contribution to the TCA cycle is a feature of aggressive Non-Small cell lung cancer in patients","volume":"15","author":"Cai","year":"2025","journal-title":"Cancer Discov"},{"key":"key20260917101257_b8-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1007\/s00109-021-02096-w","article-title":"High glucose: An emerging association between diabetes mellitus and cancer progression","volume":"99","author":"Supabphol","year":"2021","journal-title":"J Mol Med (Berl)"},{"key":"key20260917101257_b9-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/s41586-020-03045-2","article-title":"Metabolic support of tumour-infiltrating regulatory T cells by lactic acid","volume":"591","author":"Watson","year":"2021","journal-title":"Nature"},{"key":"key20260917101257_b10-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"3823","DOI":"10.1038\/s41467-023-38921-8","article-title":"Increased glucose availability sensitizes pancreatic cancer to chemotherapy","volume":"14","author":"Vaziri-Gohar","year":"2023","journal-title":"Nat Commun"},{"key":"key20260917101257_b11-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"667435","DOI":"10.3389\/fcell.2021.667435","article-title":"The absence of PTEN in breast cancer is a driver of MLN4924 resistance","volume":"9","author":"Du","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"key20260917101257_b12-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41422-021-00470-4","article-title":"Neddylation of PTEN regulates its nuclear import and promotes tumor development","volume":"31","author":"Xie","year":"2021","journal-title":"Cell Res"},{"key":"key20260917101257_b13-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"e7382","DOI":"10.1002\/cam4.7382","article-title":"High glucose inhibits autophagy and promotes the proliferation and metastasis of colorectal cancer through the PI3K\/AKT\/mTOR pathway","volume":"13","author":"Li","year":"2024","journal-title":"Cancer Med"},{"key":"key20260917101257_b14-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1038\/s41388-025-03468-z","article-title":"PTEN neddylation aggravates CDK4\/6 inhibitor resistance in breast cancer","volume":"44","author":"Liu","year":"2025","journal-title":"Oncogene"},{"key":"key20260917101257_b15-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.1093\/neuonc\/noac067","article-title":"PTEN loss drives resistance to the neddylation inhibitor MLN4924 in glioblastoma and can be overcome with TOP2A inhibitors","volume":"24","author":"Ferdosi","year":"2022","journal-title":"Neuro Oncol"},{"key":"key20260917101257_b16-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"vdae104","DOI":"10.1093\/noajnl\/vdae104","article-title":"Glioblastoma vulnerability to neddylation inhibition is dependent on PTEN status, and dysregulation of the cell cycle and DNA replication","volume":"6","author":"Taylor","year":"2024","journal-title":"Neuro-oncology advances"},{"key":"key20260917101257_b17-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"5613","DOI":"10.3390\/cancers14225613","article-title":"Targeting PTEN regulation by post translational modifications","volume":"14","author":"Gonz\u00e1lez-Garc\u00eda","year":"2022","journal-title":"Cancers (Basel)"},{"key":"key20260917101257_b18-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1083\/jcb.201105009","article-title":"Ndfip1 regulates nuclear Pten import in vivo to promote neuronal survival following cerebral ischemia","volume":"196","author":"Howitt","year":"2012","journal-title":"J Cell Biol"},{"key":"key20260917101257_b19-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1093\/neuonc\/noac159","article-title":"Targeting neddylation in cancer","volume":"24","author":"Goenka","year":"2022","journal-title":"Neuro Oncol"},{"key":"key20260917101257_b20-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"943846","DOI":"10.3389\/fonc.2022.943846","article-title":"Flavokawain A reduces Tumor-initiating properties and stemness of prostate cancer","volume":"12","author":"Song","year":"2022","journal-title":"Front Oncol"},{"key":"key20260917101257_b21-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"113288","DOI":"10.1016\/j.jpba.2020.113288","article-title":"Flavokawain A inhibits prostate cancer cells by inducing cell cycle arrest and cell apoptosis and regulating the glutamine metabolism pathway","volume":"186","author":"Wang","year":"2020","journal-title":"J Pharm Biomed Anal"},{"key":"key20260917101257_b22-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"e70030","DOI":"10.1111\/1440-1681.70030","article-title":"Flavokawain A Ruthenium-p-cymene complex-induced apoptosis by the modulation of PI3K\/\u03b2-catenin\/HER2\/PARP signalling in lung cancer","volume":"52","author":"Gayen","year":"2025","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"key20260917101257_b23-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"462","DOI":"10.3390\/molecules22030462","article-title":"Induction of G2M arrest by flavokawain A, a kava chalcone, increases the responsiveness of HER2-Overexpressing breast cancer cells to herceptin","volume":"22","author":"Jandial","year":"2017","journal-title":"Molecules"},{"key":"key20260917101257_b24-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1002\/bab.2394","article-title":"Bioactivity of hamamelitannin, flavokawain A, and triacetyl resveratrol as natural compounds: Molecular docking study, anticolon cancer, and anti-Alzheimer potentials","volume":"70","author":"Zhang","year":"2023","journal-title":"Biotechnol Appl Biochem"},{"key":"key20260917101257_b25-ol-32-4-15818","first-page":"8536","article-title":"High glucose promotes tumor cell proliferation and migration in lung adenocarcinoma via the RAGE-NOXs pathway","volume":"17","author":"Liao","year":"2018","journal-title":"Molecular medicine reports"},{"key":"key20260917101257_b26-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"109399","DOI":"10.1016\/j.jnutbio.2023.109399","article-title":"High glucose enhances the aggressiveness of lung adenocarcinoma via activating epidermal growth factor receptor\/signal transducer and activator of transcription 3 pathways","volume":"119","author":"Sorin","year":"2023","journal-title":"J Nutr Biochem"},{"key":"key20260917101257_b27-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.toxrep.2014.02.002","article-title":"Dietary feeding of Flavokawain A, a Kava chalcone, exhibits a satisfactory safety profile and its association with enhancement of phase II enzymes in mice","volume":"1","author":"Li","year":"2014","journal-title":"Toxicol Rep"},{"key":"key20260917101257_b28-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/s41419-025-07499-y","article-title":"High glucose levels promote glycolysis and cholesterol synthesis via ERR\u03b1 and suppress the autophagy-lysosomal pathway in endometrial cancer","volume":"16","author":"Mao","year":"2025","journal-title":"Cell Death Dis"},{"key":"key20260917101257_b29-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(\u2212Delta Delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"key20260917101257_b30-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"102191","DOI":"10.1016\/j.arr.2024.102191","article-title":"Emerging role of NEDD8-mediated neddylation in age-related metabolic diseases","volume":"94","author":"Yu","year":"2024","journal-title":"Ageing Res Rev"},{"key":"key20260917101257_b31-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/s13046-022-02500-4","article-title":"Flavokawain A is a natural inhibitor of PRMT5 in bladder cancer","volume":"41","author":"Liu","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"key20260917101257_b32-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1210\/clinem\/dgad450","article-title":"New horizons: Epidemiology of obesity, diabetes mellitus, and cancer prognosis","volume":"109","author":"Harborg","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"key20260917101257_b33-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"107367","DOI":"10.1016\/j.phrs.2024.107367","article-title":"Metformin: From diabetes to cancer to prolongation of life","volume":"208","author":"Sirtori","year":"2024","journal-title":"Pharmacol Res"},{"key":"key20260917101257_b34-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"6700","DOI":"10.1038\/s41467-022-34391-6","article-title":"Interaction of a viral insulin-like peptide with the IGF-1 receptor produces a natural antagonist","volume":"13","author":"Moreau","year":"2022","journal-title":"Nat Commun"},{"key":"key20260917101257_b35-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"2513","DOI":"10.1158\/0008-5472.CAN-22-3023","article-title":"PTEN loss confers resistance to Anti-PD-1 therapy in Non-Small cell lung cancer by increasing tumor infiltration of regulatory T cells","volume":"83","author":"Exposito","year":"2023","journal-title":"Cancer Res"},{"key":"key20260917101257_b36-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"e175949","DOI":"10.1172\/JCI175949","article-title":"Interruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts","volume":"134","author":"Zhang","year":"2024","journal-title":"J Clin Invest"},{"key":"key20260917101257_b37-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1002\/2211-5463.12967","article-title":"SHIP2 inhibition alters redox-induced PI3K\/AKT and MAP kinase pathways via PTEN over-activation in cervical cancer cells","volume":"10","author":"Azzi","year":"2020","journal-title":"FEBS Open Bio"},{"key":"key20260917101257_b38-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"2869","DOI":"10.1007\/s11033-018-4321-6","article-title":"Regulation and modulation of PTEN activity","volume":"45","author":"Naderali","year":"2018","journal-title":"Mol Biol Rep"},{"key":"key20260917101257_b39-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/bs.acr.2021.01.006","article-title":"Autophagy and PTEN in DNA damage-induced senescence","volume":"150","author":"Sharma","year":"2021","journal-title":"Adv Cancer Res"},{"key":"key20260917101257_b40-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1186\/s40001-023-01289-y","article-title":"Neddylation inhibitor MLN4924 sensitizes head and neck squamous carcinoma cells to (S)-10-hydroxycamptothecin","volume":"28","author":"Gu","year":"2023","journal-title":"Eur J Med Res"},{"key":"key20260917101257_b41-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"4877","DOI":"10.1038\/s41388-022-02485-6","article-title":"Linear ubiquitination of PTEN impairs its function to promote prostate cancer progression","volume":"41","author":"Guo","year":"2022","journal-title":"Oncogene"},{"key":"key20260917101257_b42-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"e2205629119","DOI":"10.1073\/pnas.2205629119","article-title":"LAPTM5 mediates immature B cell apoptosis and B cell tolerance by regulating the WWP2-PTEN-AKT pathway","volume":"119","author":"Wang","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"key20260917101257_b43-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"145796","DOI":"10.1016\/j.gene.2021.145796","article-title":"Up-down regulation of HIF-1\u03b1 in cancer progression","volume":"798","author":"Rashid","year":"2021","journal-title":"Gene"},{"key":"key20260917101257_b44-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.ccell.2025.02.015","article-title":"Hypoxia inducible factor-1\u03b1 drives cancer resistance to cuproptosis","volume":"43","author":"Yang","year":"2025","journal-title":"Cancer Cell"},{"key":"key20260917101257_b45-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"8407","DOI":"10.1021\/acs.jmedchem.3c00250","article-title":"Targeting arginine methyltransferase PRMT5 for cancer therapy: Updated progress and novel strategies","volume":"66","author":"Zheng","year":"2023","journal-title":"J Med Chem"},{"key":"key20260917101257_b46-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"e114558","DOI":"10.15252\/embj.2023114558","article-title":"MST2 methylation by PRMT5 inhibits Hippo signaling and promotes pancreatic cancer progression","volume":"42","author":"Sun","year":"2023","journal-title":"EMBO J"},{"key":"key20260917101257_b47-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1038\/s41467-017-01974-7","article-title":"Identifying the ubiquitination targets of E6AP by orthogonal ubiquitin transfer","volume":"8","author":"Wang","year":"2017","journal-title":"Nat Commun"},{"key":"key20260917101257_b48-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1111\/liv.15906","article-title":"Excessive fatty acids activate PRMT5\/MDM2\/Drosha pathway to regulate miRNA biogenesis and lipid metabolism","volume":"44","author":"Hou","year":"2024","journal-title":"Liver Int"},{"key":"key20260917101257_b49-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"189169","DOI":"10.1016\/j.bbcan.2024.189169","article-title":"Cullin-RING ligase 4 in cancer: Structure, functions, and mechanisms","volume":"1879","author":"Cheng","year":"2024","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"key20260917101257_b50-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1503","DOI":"10.3109\/13880209.2015.1107104","article-title":"Flavokawains A and B from kava (Piper methysticum) activate heat shock and antioxidant responses and protect against hydrogen peroxide-induced cell death in HepG2 hepatocytes","volume":"54","author":"Pinner","year":"2016","journal-title":"Pharm Biol"},{"key":"key20260917101257_b51-ol-32-4-15818","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1021\/tx5003194","article-title":"Flavokawains A and B in Kava, Not Dihydromethysticin, Potentiate Acetaminophen-Induced Hepatotoxicity in C57BL\/6 Mice","volume":"27","author":"Narayanapillai","year":"2014","journal-title":"Chem Res Toxicol"},{"key":"key20260917101257_b52-ol-32-4-15818","first-page":"6851798","article-title":"Biological activity, hepatotoxicity, and Structure-activity relationship of kavalactones and flavokavins, the two main bioactive components in kava (Piper methysticum)","volume":"2021","author":"Wang","year":"2021","journal-title":"Evid Based Complement Alternat Med"}],"container-title":["Oncology Letters"],"original-title":[],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T07:13:41Z","timestamp":1789629221000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.spandidos-publications.com\/10.3892\/ol.2026.15818"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":52,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8,14]]}},"URL":"https:\/\/doi.org\/10.3892\/ol.2026.15818","relation":{},"ISSN":["1792-1074","1792-1082"],"issn-type":[{"value":"1792-1074","type":"print"},{"value":"1792-1082","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}