{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T16:39:56Z","timestamp":1789663196019,"version":"4.0.1"},"reference-count":66,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Recep Tayyip Erdo\u011fan University Development Foundation","award":["02025007028656"],"award-info":[{"award-number":["02025007028656"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Vitex agnus-castus has been traditionally used to treat hormonal disorders, and recent evidence suggests its potential anticancer properties. However, its effects on gastric cancer remain unclear. Methods: This study examined the cytotoxic, apoptotic, and anti-metastatic effects of hydroalcoholic Vitex agnus-castus seed extract in gastric cancer cells. Antioxidant capacity (DPPH, ABTS) and total phenolic and flavonoid contents were analyzed. Cytotoxicity was assessed using the MTT assay in HGC27, MKN45, and AGS gastric cancer cell lines and CCD-1072Sk fibroblasts. Apoptosis, mitochondrial membrane potential (MMP), and cell cycle changes were evaluated via Annexin V-FITC\/PI, Rhodamine 123, and PI staining, respectively. RT-qPCR and gene enrichment analyses were conducted to investigate the molecular mechanisms. Apoptosis-related protein expression was analyzed through enzyme-linked immunosorbent assay (ELISA). Results: The extract exhibited high antioxidant activity and a significant phenolic and flavonoid content. It reduced cell viability in a dose-dependent manner in gastric cancer cells, while exerting low toxicity in fibroblasts. It significantly increased apoptosis, induced G0\/G1-phase cell cycle arrest, upregulated pro-apoptotic genes (CASP3, CASP7, TP53, BCL2L11), and downregulated anti-apoptotic genes (XIAP, NOL3). Gene enrichment analysis highlighted pathways like apoptosis, necrosis, and cysteine endopeptidase activity. The extract also disrupted MMP, inhibited migration and spheroid formation, suppressed EMT markers (SNAIL, SLUG, TWIST1, N-CADHERIN), and upregulated E-CADHERIN. The expression of Caspase 3 and Bax proteins increased and Bcl2 protein decreased. Conclusions: These findings suggest that Vitex agnus-castus seed extract exerts strong anticancer effects in gastric cancer cells by promoting apoptosis, reducing proliferation, and inhibiting migration. Further studies are warranted to explore its clinical relevance.<\/jats:p>","DOI":"10.3390\/nu17152564","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T15:09:53Z","timestamp":1754492993000},"page":"2564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Anticancer Activity of Vitex agnus-castus Seed Extract on Gastric Cancer Cells"],"prefix":"10.3390","volume":"17","author":[{"given":"\u00d6zlem","family":"T\u00fcrksoy-Terzio\u011flu","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, Hamidiye Institute of Health Sciences, University of Health Sciences-Turkey, Istanbul 34668, T\u00fcrkiye"},{"name":"Experimental Medicine Research and Application Center, University of Health Sciences Turkey, Istanbul 34662, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2649-6721","authenticated-orcid":false,"given":"Feyza","family":"Tosya","sequence":"additional","affiliation":[{"name":"Experimental Medicine Research and Application Center, University of Health Sciences Turkey, Istanbul 34662, T\u00fcrkiye"},{"name":"Department of Food Technology, Hamidiye Institute of Health Sciences, University of Health Sciences-Turkey, Istanbul 34668, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7771-2414","authenticated-orcid":false,"given":"Ay\u015fe","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Hamidiye Institute of Health Sciences, University of Health Sciences-Turkey, Istanbul 34668, T\u00fcrkiye"},{"name":"Experimental Medicine Research and Application Center, University of Health Sciences Turkey, Istanbul 34662, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4967-9416","authenticated-orcid":false,"given":"Sibel","family":"B\u00f6lek","sequence":"additional","affiliation":[{"name":"Experimental Medicine Research and Application Center, University of Health Sciences Turkey, Istanbul 34662, T\u00fcrkiye"},{"name":"Department of Food Technology, Hamidiye Institute of Health Sciences, University of Health Sciences-Turkey, Istanbul 34668, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levent","family":"G\u00fcl\u00fcm","sequence":"additional","affiliation":[{"name":"Department of Plant and Animal Production, Mudurnu S\u00fcreyya Astarc\u0131 Vocational College, Bolu Abant \u0130zzet Baysal University, Bolu 14030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6khan","family":"Terzio\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Hamidiye International School of Medicine, University of Health Sciences, Istanbul 34899, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2613-9644","authenticated-orcid":false,"given":"Yusuf","family":"Tutar","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Division of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.sajb.2021.02.001","article-title":"Vitex agnus-castus L. 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