{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:41:12Z","timestamp":1776926472592,"version":"3.51.2"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":38,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08007-2","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:47:11Z","timestamp":1773697631000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eugenoplatin (a phyto-chemo drug conjugate) targets cancer stem cells through inhibition of the \u03b2-catenin signaling in triple-negative breast cancer cells"],"prefix":"10.1186","volume":"24","author":[{"given":"Noura N.","family":"Alraouji","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Basem","family":"Al-Otaibi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohd Yasir","family":"Khan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Falah","family":"Al-Mohanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amer","family":"Al-Mazrou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taher","family":"Al-Tweigeri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim","family":"Al-Jammaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayodele A.","family":"Alaiya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Cherkaoui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-9254","authenticated-orcid":false,"given":"Abdelilah","family":"Aboussekhra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"8007_CR1","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/ijc.33588","volume":"149","author":"J Ferlay","year":"2021","unstructured":"Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Pineros M, Znaor A, Bray F. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021;149:778\u201389.","journal-title":"Int J Cancer"},{"issue":"15","key":"8007_CR2","doi-asserted-by":"publisher","first-page":"3697","DOI":"10.3390\/cancers13153697","volume":"13","author":"Q Wu","year":"2021","unstructured":"Wu Q, Siddharth S, Sharma D. Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs. Cancers. 2021;13(15):3697.","journal-title":"Cancers (Basel)"},{"key":"8007_CR3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.2147\/JEP.S267383","volume":"13","author":"PB Tchounwou","year":"2021","unstructured":"Tchounwou PB, Dasari S, Noubissi FK, Ray P, Kumar S. Advances in Our Understanding of the Molecular Mechanisms of Action of Cisplatin in Cancer Therapy. J Exp Pharmacol. 2021;13:303\u201328.","journal-title":"J Exp Pharmacol"},{"issue":"1","key":"8007_CR4","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12929-019-0518-9","volume":"26","author":"V Volarevic","year":"2019","unstructured":"Volarevic V, Djokovic B, Jankovic MG, Harrell CR, Fellabaum C, Djonov V, Arsenijevic N. Molecular mechanisms of cisplatin-induced nephrotoxicity: a balance on the knife edge between renoprotection and tumor toxicity. J Biomed Sci. 2019;26(1):25.","journal-title":"J Biomed Sci"},{"issue":"33","key":"8007_CR5","doi-asserted-by":"publisher","first-page":"13820","DOI":"10.1073\/pnas.0905718106","volume":"106","author":"CJ Creighton","year":"2009","unstructured":"Creighton CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, et al. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci U S A. 2009;106(33):13820\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8007_CR6","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.drup.2015.11.003","volume":"24","author":"JA Ferreira","year":"2016","unstructured":"Ferreira JA, Peixoto A, Neves M, Gaiteiro C, Reis CA, Assaraf YG, Santos LL. Mechanisms of cisplatin resistance and targeting of cancer stem cells: Adding glycosylation to the equation. Drug Resist Updat. 2016;24:34\u201354.","journal-title":"Drug Resist Updat"},{"key":"8007_CR7","doi-asserted-by":"crossref","unstructured":"Lee KL, Kuo YC, Ho YS, Huang YH. Triple-negative breast cancer: current understanding and future therapeutic breakthrough targeting cancer stemness. Cancers. 2019;11(9).","DOI":"10.3390\/cancers11091334"},{"issue":"3","key":"8007_CR8","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/S1040-8428(01)00219-0","volume":"42","author":"B Desoize","year":"2002","unstructured":"Desoize B, Madoulet C. Particular aspects of platinum compounds used at present in cancer treatment. Crit Rev Oncol Hematol. 2002;42(3):317\u201325.","journal-title":"Crit Rev Oncol Hematol"},{"issue":"2","key":"8007_CR9","doi-asserted-by":"publisher","first-page":"296","DOI":"10.2174\/1871520611313020016","volume":"13","author":"I Ali","year":"2013","unstructured":"Ali I, Wani WA, Saleem K, Haque A. Platinum compounds: a hope for future cancer chemotherapy. Anticancer Agents Med Chem. 2013;13(2):296\u2013306.","journal-title":"Anticancer Agents Med Chem"},{"issue":"1","key":"8007_CR10","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1186\/s13046-019-1360-3","volume":"38","author":"SS Islam","year":"2019","unstructured":"Islam SS, Aboussekhra A. Sequential combination of cisplatin with eugenol targets ovarian cancer stem cells through the Notch-Hes1 signalling pathway. J Exp Clin Cancer Res. 2019;38(1):382.","journal-title":"J Exp Clin Cancer Res"},{"issue":"3","key":"8007_CR11","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1002\/mc.22758","volume":"57","author":"SS Islam","year":"2018","unstructured":"Islam SS, Al-Sharif I, Sultan A, Al-Mazrou A, Remmal A, Aboussekhra A. Eugenol potentiates cisplatin anti-cancer activity through inhibition of ALDH-positive breast cancer stem cells and the NF-kappaB signaling pathway. Mol Carcinog. 2018;57(3):333\u201346.","journal-title":"Mol Carcinog"},{"issue":"1","key":"8007_CR12","doi-asserted-by":"publisher","first-page":"22221","DOI":"10.1038\/s41598-022-26446-x","volume":"12","author":"LE Bultum","year":"2022","unstructured":"Bultum LE, Tolossa GB, Kim G, Kwon O, Lee D. In silico activity and ADMET profiling of phytochemicals from Ethiopian indigenous aloes using pharmacophore models. Sci Rep. 2022;12(1):22221.","journal-title":"Sci Rep"},{"key":"8007_CR13","doi-asserted-by":"publisher","first-page":"108011","DOI":"10.1016\/j.jmgm.2021.108011","volume":"109","author":"CSM Chu","year":"2021","unstructured":"Chu CSM, Simpson JD, O\u2019Neill PM, Berry NG. Machine learning - Predicting Ames mutagenicity of small molecules. J Mol Graph Model. 2021;109:108011.","journal-title":"J Mol Graph Model"},{"issue":"1","key":"8007_CR14","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41420-024-02151-8","volume":"10","author":"NN Alraouji","year":"2024","unstructured":"Alraouji NN, Colak D, Al-Mohanna FH, Alaiya AA, Aboussekhra A. Endogenous osteoprotegerin (OPG) represses ERalpha and promotes stemness and chemoresistance in breast cancer cells. Cell Death Discov. 2024;10(1):377.","journal-title":"Cell Death Discov"},{"issue":"1","key":"8007_CR15","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1093\/nar\/gkl1075","volume":"35","author":"MA Al-Mohanna","year":"2007","unstructured":"Al-Mohanna MA, Al-Khalaf HH, Al-Yousef N, Aboussekhra A. The p16INK4a tumor suppressor controls p21WAF1 induction in response to ultraviolet light. Nucleic Acids Res. 2007;35(1):223\u201333.","journal-title":"Nucleic Acids Res"},{"issue":"22","key":"8007_CR16","doi-asserted-by":"publisher","first-page":"3924","DOI":"10.1080\/14786419.2023.2269465","volume":"38","author":"P Ahmad","year":"2024","unstructured":"Ahmad P, Alvi SS, Waiz M, Khan MS, Ahmad S, Khan MS. Naturally occurring organosulfur compounds effectively inhibits PCSK-9 activity and restrict PCSK-9-LDL-receptor interaction via in-silico and in-vitro approach. Nat Prod Res. 2024;38(22):3924\u201333.","journal-title":"Nat Prod Res"},{"issue":"12","key":"8007_CR17","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1021\/jm020017n","volume":"45","author":"DF Veber","year":"2002","unstructured":"Veber DF, Johnson SR, Cheng HY, Smith BR, Ward KW, Kopple KD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615\u201323.","journal-title":"J Med Chem"},{"issue":"1","key":"8007_CR18","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.canep.2009.04.009","volume":"33","author":"I Kato","year":"2009","unstructured":"Kato I, Cichon M, Yee CL, Land S, Korczak JF. African American-preponderant single nucleotide polymorphisms (SNPs) and risk of breast cancer. Cancer Epidemiol. 2009;33(1):24\u201330.","journal-title":"Cancer Epidemiol"},{"issue":"3","key":"8007_CR19","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/S0169-409X(02)00004-2","volume":"54","author":"WJ Egan","year":"2002","unstructured":"Egan WJ, Lauri G. Prediction of intestinal permeability. Adv Drug Deliv Rev. 2002;54(3):273\u201389.","journal-title":"Adv Drug Deliv Rev"},{"issue":"15","key":"8007_CR20","doi-asserted-by":"publisher","first-page":"4521","DOI":"10.7150\/jca.34374","volume":"11","author":"B Rizeq","year":"2020","unstructured":"Rizeq B, Gupta I, Ilesanmi J, AlSafran M, Rahman MM, Ouhtit A. The Power of Phytochemicals Combination in Cancer Chemoprevention. J Cancer. 2020;11(15):4521\u201333.","journal-title":"J Cancer"},{"key":"8007_CR21","doi-asserted-by":"crossref","unstructured":"Nedeljkovic M, Damjanovic A. Mechanisms of chemotherapy resistance in triple-negative breast cancer-how we can rise to the challenge. Cells. 2019;8(9).","DOI":"10.3390\/cells8090957"},{"issue":"1","key":"8007_CR22","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1186\/s12885-019-6278-9","volume":"19","author":"DP Hill","year":"2019","unstructured":"Hill DP, Harper A, Malcolm J, McAndrews MS, Mockus SM, Patterson SE, et al. Cisplatin-resistant triple-negative breast cancer subtypes: multiple mechanisms of resistance. BMC Cancer. 2019;19(1):1039.","journal-title":"BMC Cancer"},{"key":"8007_CR23","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.semcancer.2021.06.015","volume":"82","author":"Z Hua","year":"2022","unstructured":"Hua Z, White J, Zhou J. Cancer stem cells in TNBC. Semin Cancer Biol. 2022;82:26\u201334.","journal-title":"Semin Cancer Biol"},{"key":"8007_CR24","doi-asserted-by":"crossref","unstructured":"Park SY, Choi JH, Nam JS. Targeting cancer stem cells in triple-negative breast cancer. Cancers. 2019;11(7).","DOI":"10.3390\/cancers11070965"},{"issue":"1","key":"8007_CR25","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1186\/s12943-020-01276-5","volume":"19","author":"X Xu","year":"2020","unstructured":"Xu X, Zhang M, Xu F, Jiang S. Wnt signaling in breast cancer: biological mechanisms, challenges and opportunities. Mol Cancer. 2020;19(1):165.","journal-title":"Mol Cancer"},{"issue":"2","key":"8007_CR26","doi-asserted-by":"publisher","first-page":"e0117097","DOI":"10.1371\/journal.pone.0117097","volume":"10","author":"J Xu","year":"2015","unstructured":"Xu J, Prosperi JR, Choudhury N, Olopade OI, Goss KH. beta-Catenin is required for the tumorigenic behavior of triple-negative breast cancer cells. PLoS ONE. 2015;10(2):e0117097.","journal-title":"PLoS ONE"},{"key":"8007_CR27","doi-asserted-by":"crossref","unstructured":"Scioli MG, Storti G, D\u2019Amico F, Gentile P, Fabbri G, Cervelli V, Orlandi A. The role of breast cancer stem cells as a prognostic marker and a target to improve the efficacy of breast cancer therapy. Cancers. 2019;11(7).","DOI":"10.3390\/cancers11071021"},{"key":"8007_CR28","doi-asserted-by":"publisher","first-page":"705384","DOI":"10.3389\/fonc.2021.705384","volume":"11","author":"WA Abreu de Oliveira","year":"2021","unstructured":"Abreu de Oliveira WA, Moens S, El Laithy Y, van der Veer BK, Athanasouli P, Cortesi EE, et al. Wnt\/beta-Catenin Inhibition Disrupts Carboplatin Resistance in Isogenic Models of Triple-Negative Breast Cancer. Front Oncol. 2021;11:705384.","journal-title":"Front Oncol"},{"issue":"7","key":"8007_CR29","doi-asserted-by":"publisher","first-page":"2723","DOI":"10.1172\/JCI44745","volume":"121","author":"LL Marotta","year":"2011","unstructured":"Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, et al. The JAK2\/STAT3 signaling pathway is required for growth of CD44(+)CD24(-) stem cell-like breast cancer cells in human tumors. J Clin Invest. 2011;121(7):2723\u201335.","journal-title":"J Clin Invest"},{"issue":"1","key":"8007_CR30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12964-020-0527-z","volume":"18","author":"JH Ma","year":"2020","unstructured":"Ma JH, Qin L, Li X. Role of STAT3 signaling pathway in breast cancer. Cell Commun Signal. 2020;18(1):33.","journal-title":"Cell Commun Signal"},{"key":"8007_CR31","doi-asserted-by":"crossref","unstructured":"Kaltschmidt B, Witte KE, Greiner JFW, Weissinger F, Kaltschmidt C. Targeting NF-kappaB signaling in cancer stem cells: a narrative review. Biomedicines. 2022;10(2).","DOI":"10.3390\/biomedicines10020261"},{"key":"8007_CR32","doi-asserted-by":"crossref","unstructured":"Kaltschmidt C, Banz-Jansen C, Benhidjeb T, Beshay M, Forster C, Greiner J, et al. A Role for NF-kappaB in organ specific cancer and cancer stem cells. Cancers. 2019;11(5).","DOI":"10.3390\/cancers11050655"},{"key":"8007_CR33","doi-asserted-by":"publisher","first-page":"452","DOI":"10.3389\/fonc.2020.00452","volume":"10","author":"S Yousefnia","year":"2020","unstructured":"Yousefnia S, Seyed Forootan F, Seyed Forootan S, Nasr Esfahani MH, Gure AO, Ghaedi K. Mechanistic Pathways of Malignancy in Breast Cancer Stem Cells. Front Oncol. 2020;10:452.","journal-title":"Front Oncol"},{"issue":"1","key":"8007_CR34","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1007\/s10238-024-01446-5","volume":"24","author":"G Elayat","year":"2024","unstructured":"Elayat G, Selim A. Angiogenesis in breast cancer: insights and innovations. Clin Exp Med. 2024;24(1):178.","journal-title":"Clin Exp Med"},{"key":"8007_CR35","doi-asserted-by":"publisher","first-page":"838133","DOI":"10.3389\/fphar.2022.838133","volume":"13","author":"NM Ayoub","year":"2022","unstructured":"Ayoub NM, Jaradat SK, Al-Shami KM, Alkhalifa AE. Targeting Angiogenesis in Breast Cancer: Current Evidence and Future Perspectives of Novel Anti-Angiogenic Approaches. Front Pharmacol. 2022;13:838133.","journal-title":"Front Pharmacol"},{"issue":"6","key":"8007_CR36","first-page":"1747","volume":"8","author":"A Adeyinka","year":"2002","unstructured":"Adeyinka A, Nui Y, Cherlet T, Snell L, Watson PH, Murphy LC. Activated mitogen-activated protein kinase expression during human breast tumorigenesis and breast cancer progression. Clin Cancer Res. 2002;8(6):1747\u201353.","journal-title":"Clin Cancer Res"},{"issue":"5","key":"8007_CR37","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1002\/ijc.24831","volume":"126","author":"E Lopez-Knowles","year":"2010","unstructured":"Lopez-Knowles E, O\u2019Toole SA, McNeil CM, Millar EK, Qiu MR, Crea P, Daly RJ, Musgrove EA, Sutherland RL. PI3K pathway activation in breast cancer is associated with the basal-like phenotype and cancer-specific mortality. Int J Cancer. 2010;126(5):1121\u201331.","journal-title":"Int J Cancer"},{"key":"8007_CR38","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.canlet.2019.02.004","volume":"448","author":"Q He","year":"2019","unstructured":"He Q, Xue S, Tan Y, Zhang L, Shao Q, Xing L, et al. Dual inhibition of Akt and ERK signaling induces cell senescence in triple-negative breast cancer. Cancer Lett. 2019;448:94\u2013104.","journal-title":"Cancer Lett"},{"issue":"7","key":"8007_CR39","doi-asserted-by":"publisher","first-page":"716","DOI":"10.2174\/1389450120666181204165344","volume":"20","author":"PA Volkart","year":"2019","unstructured":"Volkart PA, Bitencourt-Ferreira G, Souto AA, de Azevedo WF. Cyclin-Dependent Kinase 2 in Cellular Senescence and Cancer. A Structural and Functional Review. Curr Drug Targets. 2019;20(7):716\u201326.","journal-title":"Curr Drug Targets"},{"key":"8007_CR40","doi-asserted-by":"crossref","unstructured":"You KS, Yi YW, Cho J, Seong YS. Dual inhibition of AKT and MEK pathways potentiates the anti-cancer effect of gefitinib in triple-negative breast cancer cells. Cancers (Basel). 2021;13(6).","DOI":"10.3390\/cancers13061205"},{"issue":"7","key":"8007_CR41","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1093\/annonc\/mdz133","volume":"30","author":"J Pascual","year":"2019","unstructured":"Pascual J, Turner NC. Targeting the PI3-kinase pathway in triple-negative breast cancer. Ann Oncol. 2019;30(7):1051\u201360.","journal-title":"Ann Oncol"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08007-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08007-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08007-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:53:31Z","timestamp":1776923611000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08007-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,16]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8007"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08007-2","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,16]]},"assertion":[{"value":"4 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Animal experiments were approved by the KFSH&RC Institutional Animal Care and Use Committee (ACUC) under RAC# 2220020 and were conducted according to relevant national and international guidelines.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"We declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"577"}}