{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:34:43Z","timestamp":1786977283234,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Breast cancer remains one of the most prevalent malignancies among women. Recent studies have explored the potential of phytochemicals such as caffeine as chemosensitizing agents in enhancing the efficacy of standard chemotherapeutics like paclitaxel. This study aimed to investigate the cytotoxic, apoptotic, inflammatory, and oxidative stress\u2010related effects of caffeine alone and in combination with paclitaxel in MCF\u20107 cells. Cells were treated with various concentrations of caffeine (1\u2013100\u2009mM), paclitaxel (0\u2013350\u2009\u00b5g\/mL), and their combinations for 24, 48, and 72\u2009h. Cell viability was assessed using the MTS assay, and IC\u2085\u2080 values were calculated. The expression levels of Bax, Bcl\u20102, NF\u2010\u03baB, and Nrf2 proteins were analyzed by Western blotting. Both caffeine and paclitaxel induced time\u2010 and dose\u2010dependent reductions in MCF\u20107 cell viability. The combination treatment showed synergistic cytotoxicity, with significantly lower IC\u2085\u2080 values compared to single\u2010agent treatments. Western blot analysis showed that both treatments boosted pro\u2010apoptotic Bax and decreased anti\u2010apoptotic Bcl\u20102, with slightly less effect in the combination group. NF\u2010\u03baB levels increased considerably in caffeine and paclitaxel groups, but were lower in the combination group compared to paclitaxel alone, suggesting a possible reduction in inflammatory signaling. Nrf2 expression increased significantly with caffeine, suggesting oxidative stress responses. In MCF\u20107 cells, caffeine enhanced paclitaxel's pro\u2010apoptotic and cytotoxic actions and modified inflammation and oxidative stress pathways in a complicated, dose\u2010dependent manner. Cytotoxicity was synergistic; however, apoptotic and stress indicators may be antagonistic. In clinical circumstances, caffeine may be an adjuvant in breast cancer treatment, however mechanistic and in vivo investigations are needed.<\/jats:p>","DOI":"10.1002\/cbf.70183","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T08:41:10Z","timestamp":1771490470000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic Effects of Caffeine and Paclitaxel in Breast Cancer Cells: Mechanistic Insights Into NF\u2010\u03baB and Nrf2 Signaling"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7716-552X","authenticated-orcid":false,"given":"Hasan","family":"Gencoglu","sequence":"first","affiliation":[{"name":"Biology &amp; Molecular Biology and Genetics, Science Faculty Firat University  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saime","family":"Delioglu","sequence":"additional","affiliation":[{"name":"Biology &amp; Molecular Biology and Genetics, Science Faculty Firat University  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Akif","family":"Nergiz","sequence":"additional","affiliation":[{"name":"Biology &amp; Molecular Biology and Genetics, Science Faculty Firat University  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumeysa","family":"Metin","sequence":"additional","affiliation":[{"name":"Biology &amp; Molecular Biology and Genetics, Science Faculty Firat University  Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fusun","family":"Erten","sequence":"additional","affiliation":[{"name":"Department of Veterinary Science, Pertek Sakine Genc Vocational School Munzur University Tunceli Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed","family":"Tokmak","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine Firat University Elazig Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cemal","family":"Orhan","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine Firat University Elazig Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9542-5244","authenticated-orcid":false,"given":"Kazim","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine Firat University Elazig Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu15122666"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184360"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2020.1795693"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.55262\/fabadeczacilik.1164699"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2024.42.16_suppl.e13148"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2021.1919782"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA05089D"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28145578"},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","unstructured":"F.Burdan \u201cPharmacology of Caffeine: The Main Active Compound of Coffee \u201d in Coffee in Health and Disease Prevention ed. V. R. Preedy (Academic Press 2015) 823\u2013829 https:\/\/doi.org\/10.1016\/B978-0-12-409517-5.00090-5.","DOI":"10.1016\/B978-0-12-409517-5.00090-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2FO00983H"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13060657"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12684"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9090902"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252212003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21464"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2219333"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534735418801521"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-024-00846-4"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201801239"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/agaa012"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2008.00231.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-4180-x"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.6894"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2013.1763"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.135513"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2174\/2211738507666190122111224"},{"key":"e_1_2_10_28_1","first-page":"3147","article-title":"The Story of MCF\u20107 Breast Cancer Cell Line: 40 Years of Experience in Research","volume":"35","author":"Com\u015fa \u015e.","year":"2015","journal-title":"Anticancer Research"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv073"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djq361"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.29228\/jrp.513"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2017.1324994"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03433-5"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.26502\/acbr.50170077"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/1534735419901160"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2018.8868"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2017.6024"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19970117)70:2<214::AID-IJC13>3.0.CO;2-I"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2022-0303"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110441"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10102668"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232113074"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29143302"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/2162-3619-4-5"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00776-009-1372-5"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.05.144"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155120"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70183","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbf.70183","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70183","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T10:54:38Z","timestamp":1772967278000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.70183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":46,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/cbf.70183"],"URL":"https:\/\/doi.org\/10.1002\/cbf.70183","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70183"}}