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In this study, we report the synthesis and biological evaluation of glycoconjugate vanadyl complexes as GLUT-directed anticancer agents against breast cancer. A Schiff base ligand (CG) was synthesized through the condensation of curcumin (C) and glucosamine (G), followed by complexation with vanadyl to form [VO(CG)\u2082]\u00b75H\u2082O. The synthesized compounds were comprehensively characterized by elemental analysis, MS, NMR, FT-IR, TGA, molar conductance, and magnetic susceptibility measurements. Spectroscopic and computational studies confirmed that the ligand coordinates in a bidentate chelating mode via the azomethine nitrogen and the enolic oxygen. Biological evaluation in MCF-7 breast cancer cells included cytotoxicity assays, molecular docking, DNA-binding studies, and quantitative gene expression analysis. Both compounds exhibited cytotoxic activity, with the CG ligand showing the highest potency (IC\u2085\u2080\u2009=\u20097.51\u2009\u00b1\u20090.12 \u03bcg\/mL or 14.2 \u03bcM). Notably, co-treatment with the GLUT inhibitor quercetin significantly increased the IC\u2085\u2080 value, suggesting the involvement of GLUT-mediated cellular uptake. Molecular docking studies indicated favorable binding affinity toward GLUT, while DNA-binding experiments demonstrated interaction with DNA. Treatment of MCF-7 cells with the glycoconjugate ligand induced DNA damage, modulated the expression of cell cycle- and apoptosis-related genes, and promoted apoptosis. Flow cytometric analysis demonstrated that the glycoconjugate significantly arrested MCF-7 cells in the S-phase (49.40% vs 22.22% in control). This finding is consistent with impaired cell cycle progression and may be associated with the observed DNA interaction. Quantitative real-time PCR analysis of the CG compound revealed significant upregulation of BAX and CDKN1A (p21) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.05) and pronounced upregulation of STK11 (LKB1) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009\u2264\u20090.001), suggesting activation of the AMPK signaling pathway and a metabolic stress response. Overall, the glycoconjugate ligand induces apoptosis and cell cycle arrest through oxidative and metabolic stress mediated by AMPK\u2013STK11 signaling, highlighting its potential as a GLUT-targeted chemotherapeutic agent for breast cancer treatment.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-65680-5","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:15:31Z","timestamp":1786691731000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Glycoconjugate strategy for GLUT-driven curcumin delivery and anticancer activity in breast cancer cells"],"prefix":"10.1038","volume":"16","author":[{"given":"Safaa S.","family":"Hassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma B.","family":"Rashidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramy G.","family":"Seddik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Areej W.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Habiba A.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hager W.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menna M.","family":"Kenawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouran B.","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nourhan A.","family":"Afify","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura M.","family":"Megahed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem M.","family":"Zeinhom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziad A.","family":"Abdultawab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayatallah","family":"Elgohary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nashwa","family":"Hamido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed I.","family":"Elwakil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel A.","family":"Alzoghaly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina O.","family":"Nabil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab A.","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaled M.","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"issue":"6","key":"65680_CR1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.3892\/mco.2021.2433","volume":"15","author":"SM Alzahrani","year":"2021","unstructured":"Alzahrani, S. 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