{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T09:13:39Z","timestamp":1764666819346,"version":"3.46.0"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Breast cancer remains the most commonly diagnosed cancer and a leading cause of cancer\u2010related mortality among women worldwide. Despite advancements in treatment, resistance and toxicity issues highlight the urgent need for novel, effective, and safer therapeutic agents. Natural compounds are increasingly explored as promising sources of anticancer candidates due to their structural diversity and bioactivity. Among these, polyols, a class of sugar alcohols, have been reported to influence cancer cell behaviour by modulating oxidative stress, metabolic pathways and apoptosis, though their precise mechanisms and therapeutic potential remain underexplored. In this study, the anticancer potential of dulcitol, a naturally occurring polyol, was investigated in breast cancer cell lines with different molecular profiles. The cytotoxic effects of dulcitol were assessed using the MTT assay in MCF\u20107 (ER\u2010positive), MDA\u2010MB\u2010231 (triple\u2010negative), and MCF\u201010A (non\u2010tumorigenic) breast cell lines. Mechanistic studies including flow cytometry\u2010based cell cycle analysis, apoptosis detection (Annexin V\u2010FITC), mitochondrial membrane potential assessment, caspase activation, and DNA damage analysis were performed on MDA\u2010MB\u2010231 cells. The expression levels of MMP\u20102 and MMP\u20109 genes were also evaluated using qRT\u2010PCR. Dulcitol exhibited selective cytotoxicity against MDA\u2010MB\u2010231 cells at concentrations \u2265\u20097.5\u2009mmol\/L, while showing no significant effects on MCF\u20107 and MCF\u201010A cells. In MDA\u2010MB\u2010231 cells, dulcitol induced G0\/G1 phase cell cycle arrest and promoted apoptosis in a dose\u2010dependent manner. Additionally, increased caspase activity and mitochondrial depolarization were observed, indicating activation of the intrinsic apoptotic pathway. No significant DNA damage was detected; however, a significant downregulation of MMP\u20102 and MMP\u20109 expression suggested potential antimetastatic activity. Although the effective in vitro concentrations were relatively high, it should be noted that such levels are commonly required to reveal mechanistic effects in cell\u2010based systems, and pharmacokinetic data on dulcitol are currently unavailable. Therefore, the present findings should be regarded as exploratory and hypothesis\u2010generating, emphasizing the need for in vivo pharmacokinetic and efficacy studies to evaluate translational feasibility. In conclusion, our findings demonstrate that dulcitol selectively targets triple\u2010negative breast cancer cells without affecting normal or ER\u2010positive breast cells. Its ability to induce apoptosis and suppress metastatic gene expression highlights its promise as a potential natural therapeutic candidate for aggressive breast cancer subtypes.<\/jats:p>","DOI":"10.1002\/cbf.70134","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:56:24Z","timestamp":1761663384000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dulcitol Selectively Inhibits Proliferation and Metastasis Related Markers in Triple\u2010Negative Breast Cancer: Uncovering an Unforeseen Activity"],"prefix":"10.1002","volume":"43","author":[{"given":"Betul","family":"Yanik","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Ankara University Faculty of Pharmacy Ankara T\u00fcrkiye"},{"name":"Ankara University Institute of Health Sciences Ankara T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filiz","family":"Bakar\u2010Ates","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Ankara University Faculty of Pharmacy Ankara T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adcanc.2022.100086"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.12284"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2015.08.001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4510"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_9_8_1","first-page":"1","article-title":"Current Developments in Sugar Alcohols: Chemistry, Nutrition, and Health Concerns of Sorbitol, Xylitol, Glycerol, Arabitol, Inositol, Maltitol, and Lactitol","volume":"5","author":"Awuchi C. G.","year":"2019","journal-title":"International Journal of Advanced Academic Research"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0890-6238(00)00096-4"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym16223229"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12070968"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.153112"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2025.106797"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2014.1994"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109085"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods9111592"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2019.02.010"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1108695"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2014.12.002"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-020-10929-w"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-007-0261-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/07357908509039794"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10529-014-1757-1"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14102023"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2017.1339097"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021582"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bjaceaccp\/mkr063"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2004.04.034"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells12060825"},{"issue":"1","key":"e_1_2_9_30_1","first-page":"9","article-title":"Induction of G0\/G1 Phase Arrest and Apoptosis by CRISPR\/Cas9\u2010mediated Knockout of CDK2 in A375 Melanocytes","volume":"12","author":"Liu H.","year":"2020","journal-title":"Molecular and Clinical Oncology"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.770846"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-05955-0"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells13221838"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","unstructured":"E.Dogan H. G.Kara B.Kosova andV. B.CetintasTargeting Apoptosis to Overcome Chemotherapy Resistance. In: Sergi CM editor. Metastasis [Internet]. Brisbane (AU): Exon Publications;2022May 3. Chapter 12.","DOI":"10.36255\/exon-publications.metastasis.chemotherapy-resistance"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a026716"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201963200"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.896099"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2011.10.001"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252413691"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-1768166"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.1932"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2013.1917"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0394-9508.23.05589-4"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.05.209"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25169042"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwae288"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1079\/NRR200371"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.117.015560"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.218"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaf091"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41538-025-00410-1"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.70134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T09:08:45Z","timestamp":1764666525000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.70134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":50,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/cbf.70134"],"URL":"https:\/\/doi.org\/10.1002\/cbf.70134","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"type":"print","value":"0263-6484"},{"type":"electronic","value":"1099-0844"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"assertion":[{"value":"2025-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70134"}}