{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:47:33Z","timestamp":1782110853867,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study investigated the effects of lutein, a natural carotenoid, and the chemotherapeutic agent cisplatin on three cell lines: HUVEC (non\u2010cancerous), MDA\u2010MB\u2010231 (ER\u2212 breast cancer), and MCF\u20107 (ER+ breast cancer). Cells were treated with lutein, cisplatin, or both for 24 and 48\u2009h. Cell viability was evaluated using the MTT assay; oxidative DNA damage was assessed via 8\u2010OHdG levels; apoptosis was determined by caspase\u20103 protein level; and DNA damage response (DDR) gene expression was analyzed through real\u2010time PCR. Lutein exhibited time\u2010 and cell type\u2013dependent cytotoxicity. It significantly reduced viability in MDA\u2010MB\u2010231 cells and showed a mild effect in MCF\u20107 cells, while in HUVECs, cytotoxicity was more evident in the combination group. Lutein elevated oxidative DNA damage in cancer cells but had minimal effect in HUVECs; this pro\u2010oxidant activity persisted in combination with cisplatin. Caspase\u20103 level was notably increased in MDA\u2010MB\u2010231 cells, correlating with cell death. At the gene expression level, cisplatin consistently upregulated DDR genes, while lutein exerted suppressive or variable effects depending on the gene and cell type. In MCF\u20107 cells, lutein downregulated key repair genes such as BRCA1, XRCC1 and XRCC6, while its combination with cisplatin notably upregulated ATM and RAD51, suggesting potential synergistic interaction through modulation of estrogen\u2010related DNA repair. In contrast, MDA\u2010MB\u2010231 cells displayed increased DDR gene expression following combination treatment, indicating a possible reduction in cisplatin sensitivity. Synergy analysis revealed that the interaction between lutein and cisplatin was largely additive in MDA\u2010MB\u2010231 cells, mildly synergistic in HUVECs, and highly variable in MCF\u20107 cells, ranging from synergistic to antagonistic responses. Overall, these findings suggest that lutein modulates DNA repair pathways in a cell\u2010specific manner and may alter the efficacy of chemotherapeutic regimens depending on the hormonal and genetic background of the tumor.<\/jats:p>","DOI":"10.1002\/jbt.70926","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:44:07Z","timestamp":1780465447000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lutein Influences Cisplatin Sensitivity Through Differential Regulation of DNA Damage Response Genes in Breast Cancer Cells"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3978-9427","authenticated-orcid":false,"given":"Funda","family":"Demirtas Korkmaz","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Giresun University Giresun Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zekeriya","family":"Duzgun","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine Giresun University Giresun Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysegul","family":"Cebi","sequence":"additional","affiliation":[{"name":"Department of Midwifery, Faculty of Health Sciences Giresun University Giresun Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr980421n"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1206933"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.07.025"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/nure.12133"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.23.011702.073307"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6235641"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10091448"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112328"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23040905"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2017.06.041"},{"issue":"1","key":"e_1_2_9_13_1","first-page":"147","article-title":"Effect of Lutein\u2010Rich Extract on Human Cancer Cells","volume":"12","author":"Omar W. 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