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Current treatments including surgery and chemotherapy are limited by side effects and chemoresistance, underscoring the need for novel therapies. This study aimed to investigate the antitumor potential of resveratrol (RSV), a natural polyphenol, as a novel treatment for OS. The effects of RSV were evaluated in two osteosarcoma cell lines (SAOS\u20102 and U2\u2010OS). A viability assay established 100\u2009\u03bcM as the effective concentration, and hyperspectral imaging confirmed cellular uptake. Apoptosis was measured via caspase\u20103\/7 activity and Annexin V\/PI staining, while qRT\u2010PCR assessed pro\u2010apoptotic gene expression. Flow cytometry evaluated cell\u2010cycle progression, and a wound\u2010healing assay measured migration. Gene expression analyses (qRT\u2010PCR) examined markers of cell adhesion, tumour progression and epithelial\u2013mesenchymal transition. Finally, RSV's impact on the Wnt\/\u03b2\u2010catenin pathway was determined by quantifying nuclear \u03b2\u2010catenin accumulation and the expression of its downstream oncogenic targets. RSV inhibited cell proliferation and induced apoptosis, increasing caspase\u20103\/7 activity and modulating apoptotic gene expression. RSV also caused cell cycle arrest in S\u2010phase. It reduced the cells' migration and altered the expression of cell adhesion and tumour progression genes, promoting a less invasive phenotype. Notably, RSV decreased nuclear \u03b2\u2010catenin accumulation, downregulated oncogenic targets like c\u2010Myc and MMPs, and upregulated E\u2010cadherin while reducing vimentin levels, suggesting a reversal of epithelial\u2013mesenchymal transition. These results suggest that RSV may offer a promising therapeutic approach for osteosarcoma, modulating key pathways involved in tumour progression, metastasis and chemoresistance. Further studies are required to assess its clinical applicability.<\/jats:p>","DOI":"10.1111\/jcmm.71111","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T07:08:23Z","timestamp":1775459303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gene Expression Alterations Associated With Resveratrol\u2010Induced Antiproliferative Effects and S\u2010Phase Cell Cycle Arrest in Osteosarcoma Cancer Cells"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1485-8950","authenticated-orcid":false,"given":"Raffaella","family":"De Pace","sequence":"first","affiliation":[{"name":"Department of Translational Medicine University of Ferrara  Ferrara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-859X","authenticated-orcid":false,"given":"Maria 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