{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T22:33:42Z","timestamp":1789252422695,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Glioblastoma (GB) is a highly aggressive brain tumour with a poor prognosis and limited responsiveness to standard chemotherapy, particularly temozolomide (TMZ), due to intrinsic resistance mechanisms. This study investigates the potential of\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">Aesculus hippocastanum<\/jats:styled-content>\n                      ,\n                    <\/jats:italic>\n                    known as horse chestnut extract (HCE), to enhance the therapeutic efficacy of TMZ in GB cells through modulation of the Wnt\/\u03b2\u2010catenin signalling pathway. Combined treatment of HCE (500\u2009\u03bcg\/mL) and TMZ (100\u2009\u03bcM) significantly reduced cell viability and inhibited wound healing and colony formation compared to either agent alone at 48\u2009h. Notably, the expression of \u03b2\u2010catenin and Wnt\u20101 was significantly reduced in the combination group, followed by a significant downregulation of Nestin and \u03b23\u2010tubulin, markers of glioma stem\u2010like cells and aggressiveness, respectively. Furthermore, apoptotic activity was significantly increased following the combined treatment. In a 3D U87\u2010spheroid model, the combination therapy resulted in a substantial reduction in spheroid area, suggesting impaired tumour growth. Propidium iodide (PI) staining revealed increased membrane permeability in cells treated with the combination, which was accompanied by an increase in p53 expression, supporting the induction of apoptosis. Collectively, these findings demonstrate that HCE increases the cytotoxic effects of TMZ by inhibiting Wnt\/\u03b2\u2010catenin signalling, reducing tumour stemness, and promoting apoptotic pathways in GB cells.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70979","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T08:45:57Z","timestamp":1771231557000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Modulation of Wnt\/\u03b2\u2010Catenin Pathway by\n                    <scp>\n                      <i>Aesculus hippocastanum<\/i>\n                    <\/scp>\n                    Extract Enhances Temozolomide Sensitivity in Glioblastoma Cells"],"prefix":"10.1111","volume":"30","author":[{"given":"Sarah Adriana","family":"Scuderi","sequence":"first","affiliation":[{"name":"Genetics and Pharmacogenetics Unit \u201cGaetano Martino\u201d University Hospital  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Ardizzone","sequence":"additional","affiliation":[{"name":"UniCamillus\u2010Saint Camillus International University of Health Sciences  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Mannino","sequence":"additional","affiliation":[{"name":"Research Operative Unit of Neuropharmacology and Translational Neurosciences Oasi Research Institute, IRCCS  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicoletta","family":"Palermo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Catalfamo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Campolo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-6387","authenticated-orcid":false,"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Paterniti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-99-3378-5_29"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00419"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16091637"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13111536"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2022.2125302"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12094-016-1497-x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2018.11.031"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030484"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/glioma.glioma_3_19"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.5964"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15133458"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/13816128113199990493"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-9-135"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-020-01432-7"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031353"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110350"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2015.140"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.650772"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2025.117411"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12182284"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12060841"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13040361"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13112765"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1401979"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/09731296241299498"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13020315"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-023-01849-x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/251752"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.192"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25081917"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-021-04380-5"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.4688"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17081102"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26062579"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213915"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11030352"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.059882"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2024.1471012"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13143444"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncoscience.171"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.203662"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2022.120609"},{"issue":"1","key":"e_1_2_11_44_1","first-page":"17","article-title":"Mechanisms of Temozolomide Resistance in Glioblastoma \u2010 a Comprehensive Review","volume":"4","author":"Singh N.","year":"2021","journal-title":"Cancer Drug Resistance"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12017-018-8514-x"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-010-9476-5"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.963614"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0181346"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.32"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-014-0408-8"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/9628289"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152011797378760"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-524"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01839-8"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.011635"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060950"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2022.105281"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.742483"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70979","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.70979","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.70979","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T14:32:47Z","timestamp":1773930767000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.70979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/jcmm.70979"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.70979","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-09-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70979"}}