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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Obesity-driven hyperleptinemia is a key driver of breast cancer (BC) aggressiveness; nevertheless, strategies to counteract leptin-mediated tumor progression remain limited. Curcumin, a natural polyphenol with established anti-obesity, anti-inflammatory, and anticancer properties, has emerged as a promising metabolic and tumor-modulating biomolecule, although its effects on leptin-induced oncogenic signaling remain unclear. This study evaluated Curcumin as an adjuvant nutraceutical against leptin-induced oncogenesis in MCF-7 and MDA-MB-231 cells. Cells were exposed to obesity-mimicking leptin levels alone or with non-toxic Curcumin doses. MTT, clonogenic, wound-healing, and 3D spheroid dissemination assays were used to assess phenotypic changes, while network pharmacology and molecular docking explored underlying mechanisms. Curcumin significantly inhibited leptin-induced proliferation (8\u201317%), colony formation (60\u201390%), migration (20\u201345%), and 3D spheroid dissemination (20%) in both BC cell lines. Network pharmacology identified shared hub proteins, including AKT1, RHOA, MAP2K1, and MAPK14, linking Curcumin targets with leptin-driven BC signatures, and molecular docking supported direct interactions of Curcumin with these proteins. These findings suggest that Curcumin counteracts hyperleptinemia-induced tumor progression by targeting the PI3K\/AKT, MAPK\/ERK, and RHOA\/ROCK pathways. This integrated in vitro and in silico study supports Curcumin as a promising adjuvant nutraceutical for obesity-associated BC, although experimental pathway validation is still required.<\/jats:p>","DOI":"10.3390\/ijms27198572","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:09:02Z","timestamp":1790323742000},"page":"8572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting Obesity-Associated Breast Cancer: Curcumin Counteracts Leptin-Induced Tumorigenic and Metastatic Traits in MCF-7 and MDA-MB-231 Breast Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Han\u00e8ne","family":"Attia","sequence":"first","affiliation":[{"name":"Laboratory of Genetics, Immunology, and Human Pathologies, Faculty of Sciences of Tunis, University Tunis El Manar, Tunis 1068, 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