{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:10:29Z","timestamp":1787069429480,"version":"build-2736575974"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Breast cancer (BC) remains the most diagnosed malignancy among women worldwide, with approximately 2.3 million new cases and over 670,000 deaths reported annually. Resistance to conventional chemotherapeutic agents and treatment-related toxicity remain major challenges in BC management. Resveratrol, a naturally occurring polyphenol, has been proposed as a potential modulator of chemotherapy response; however, comparative evidence regarding its interaction with different classes of chemotherapeutic agents is limited. This study aimed to comparatively assess the effects of resveratrol on the cytotoxic, antiproliferative, and apoptotic responses induced by adriamycin, taxol, and cisplatin in MCF-7 BC cells. MCF-7 cells were treated with adriamycin, taxol, cisplatin, and resveratrol, either alone or in combination, across multiple concentrations for 24, 48, 72, and 96 h. Cell viability was evaluated using the trypan blue exclusion assay. Cellular proliferation was assessed via BrdU incorporation, while apoptosis and cell death profiles were analyzed using Annexin V staining and flow cytometry. Exposure to individual chemotherapeutic agents induced a significant time- and dose-dependent reduction in MCF-7 cell viability (p &lt; 0.001). Resveratrol co-treatment further modulated chemotherapy-induced cytotoxicity in an agent- and time-dependent manner. Combination treatments markedly suppressed DNA synthesis compared with single-agent exposure (p &lt; 0.01) and significantly increased apoptotic cell populations. Flow cytometric Annexin V\/PI analysis demonstrated that early apoptotic cells ranged from 3.2\u201311.3% in single-agent treatments and increased to 0.04\u201350.4% in resveratrol-based combination groups. Similarly, late apoptotic\/secondary necrotic cell fractions increased from 4.1\u20134.4% in single-agent treatments to 2.1\u201369.9% following combination therapy, indicating a substantially higher overall cell death response in selected treatment conditions. This study demonstrates that resveratrol modulates the cytotoxic and apoptotic responses of MCF-7 BC cells to adriamycin, taxol, and cisplatin in an agent- and time-dependent manner. The findings indicate that resveratrol acts as a context-dependent modulator of chemotherapy response. Although resveratrol generally enhanced cytotoxic and apoptotic responses in combination treatments, the magnitude of these effects varied depending on the chemotherapeutic agent and exposure conditions. Further preclinical and clinical studies are warranted to define their therapeutic relevance.<\/jats:p>","DOI":"10.3390\/ijms27072979","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T13:48:41Z","timestamp":1774532921000},"page":"2979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Resveratrol as a Modulator of Adriamycin-, Taxol-, and Cisplatin-Induced Cytotoxicity in MCF-7 Breast Cancer Cells"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8435-6797","authenticated-orcid":false,"given":"Burcu","family":"Biltekin","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1347-8498","authenticated-orcid":false,"given":"Hafize","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9399-5927","authenticated-orcid":false,"given":"Ayhan","family":"Bilir","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Istanbul Atlas University, Istanbul 34403, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","first-page":"e70043","article-title":"Cancer statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J Clin."},{"key":"ref_2","first-page":"477","article-title":"Breast cancer statistics 2024","volume":"74","author":"Giaquinto","year":"2024","journal-title":"CA Cancer J. 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