{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T09:23:23Z","timestamp":1787304203518,"version":"build-2736575974"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100007771","name":"Medical University of Silesia in Katowice","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007771","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010252","name":"Medical University of Silesia","doi-asserted-by":"publisher","award":["BNW-2-013\/K\/6\/F"],"award-info":[{"award-number":["BNW-2-013\/K\/6\/F"]}],"id":[{"id":"10.13039\/501100010252","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010252","name":"Medical University of Silesia","doi-asserted-by":"publisher","award":["BNW-1-006\/K\/6\/F"],"award-info":[{"award-number":["BNW-1-006\/K\/6\/F"]}],"id":[{"id":"10.13039\/501100010252","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010252","name":"Medical University of Silesia","doi-asserted-by":"publisher","award":["BNW-2-012\/N\/6\/F"],"award-info":[{"award-number":["BNW-2-012\/N\/6\/F"]}],"id":[{"id":"10.13039\/501100010252","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology and Applied Pharmacology"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.taap.2026.117969","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:34:17Z","timestamp":1784763257000},"page":"117969","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Mechanistic insights into EB171 anticancer activity in MCF7 and MDA-MB-231 breast cancer cells showing differential responses"],"prefix":"10.1016","volume":"515","author":[{"given":"Zuzanna","family":"Rzepka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Stencel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"B\u0119benek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota","family":"Wrze\u015bniok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.taap.2026.117969_bb0005","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejps.2006.04.006","article-title":"Pharmacological properties of the ubiquitous natural product betulin","volume":"29","author":"Alakurtti","year":"2006","journal-title":"Eur. J. Pharm. Sci."},{"issue":"13","key":"10.1016\/j.taap.2026.117969_bb0010","doi-asserted-by":"crossref","DOI":"10.1016\/j.heliyon.2024.e33665","article-title":"Flow cytometry-based quantitative analysis of cellular protein expression in apoptosis subpopulations: a protocol","volume":"10","author":"Alshehade","year":"2024","journal-title":"Heliyon"},{"issue":"8","key":"10.1016\/j.taap.2026.117969_bb0015","doi-asserted-by":"crossref","first-page":"4517","DOI":"10.3390\/ijms25084517","article-title":"Synthesis, pharmacokinetic profile, anticancer activity and toxicity of the new amides of Betulonic acid\u2014in silico and in vitro study","volume":"25","author":"B\u0119benek","year":"2024","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"10.1016\/j.taap.2026.117969_bb0020","doi-asserted-by":"crossref","DOI":"10.3390\/medicina61071280","article-title":"Current endocrine therapy in hormone-receptor-positive breast cancer: from tumor biology to the rationale for therapeutic tunning","volume":"61","author":"Burciu","year":"2025","journal-title":"Medicina"},{"issue":"6","key":"10.1016\/j.taap.2026.117969_bb0025","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1056\/NEJMoa2505725","article-title":"Vepdegestrant, a PROTAC Estrogen receptor degrader, in advanced breast cancer","volume":"393","author":"Campone","year":"2025","journal-title":"N. Engl. J. Med."},{"issue":"7","key":"10.1016\/j.taap.2026.117969_bb0030","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.3390\/cancers17071102","article-title":"Molecular subtypes and mechanisms of breast Cancer: precision medicine approaches for targeted therapies","volume":"17","author":"Carvalho","year":"2025","journal-title":"Cancers"},{"key":"10.1016\/j.taap.2026.117969_bb0035","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/med.10053","article-title":"Chemistry, biological activity, and chemotherapeutic potential of betulinic acid and its derivatives","volume":"24","author":"Cichewicz","year":"2004","journal-title":"Med. Res. Rev."},{"issue":"4","key":"10.1016\/j.taap.2026.117969_bb0040","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.ejps.2012.08.012","article-title":"Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways","volume":"47","author":"Farabegoli","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.taap.2026.117969_bb0045","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jep.2015.03.039","article-title":"Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53\/p21 and mitochondrial signalling pathway","volume":"166","author":"Foo","year":"2015","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.taap.2026.117969_bb0050","doi-asserted-by":"crossref","DOI":"10.3389\/fpubh.2025.1622954","article-title":"Global burden and projections of breast cancer incidence and mortality to 2050: a comprehensive analysis of GLOBOCAN data","volume":"13","author":"Freihat","year":"2025","journal-title":"Front. Public Health"},{"key":"10.1016\/j.taap.2026.117969_bb0055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mrgentox.2018.02.003","article-title":"Betulinic acid induces DNA damage and apoptosis in SiHa cells","volume":"828","author":"Goswami","year":"2018","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"issue":"1","key":"10.1016\/j.taap.2026.117969_bb0060","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1093\/jbi\/wbaa110","article-title":"Molecular subtypes of breast cancer: a review for breast radiologists","volume":"3","author":"Johnson","year":"2021","journal-title":"J. Breast Imaging"},{"key":"10.1016\/j.taap.2026.117969_bb0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.117126","article-title":"Triterpenoid phthalimides as selective anti-cancer agents targeting mitochondrial apoptosis","volume":"283","author":"Kazakova","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.taap.2026.117969_bb0070","doi-asserted-by":"crossref","first-page":"1564642","DOI":"10.3389\/or.2025.1564642","article-title":"Treating ER-positive breast cancer: a review of the current FDA-approved SERMs and SERDs and their mechanisms of action","volume":"19","author":"Kim","year":"2025","journal-title":"Oncol. Rev."},{"issue":"2","key":"10.1016\/j.taap.2026.117969_bb0075","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.bbrc.2014.07.115","article-title":"Inhibition of estrogen signaling through depletion of estrogen receptor alpha by ursolic acid and betulinic acid from Prunella vulgaris var. lilacina","volume":"451","author":"Kim","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"4","key":"10.1016\/j.taap.2026.117969_bb0080","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1038\/s41591-025-03502-3","article-title":"Global patterns and trends in breast cancer incidence and mortality across 185 countries","volume":"31","author":"Kim","year":"2025","journal-title":"Nat. Med."},{"key":"10.1016\/j.taap.2026.117969_bb0085","doi-asserted-by":"crossref","DOI":"10.1177\/17588359221113694","article-title":"Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role","volume":"14","author":"Lloyd","year":"2022","journal-title":"Ther. Adv. Med. Oncol."},{"issue":"17","key":"10.1016\/j.taap.2026.117969_bb0090","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.3390\/cancers13174287","article-title":"Breast cancer\u2014epidemiology, risk factors, classification, prognostic markers, and current treatment strategies\u2014an updated review","volume":"13","author":"\u0141ukasiewicz","year":"2021","journal-title":"Cancers"},{"issue":"1","key":"10.1016\/j.taap.2026.117969_bb0095","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41523-022-00483-1","article-title":"Elacestrant demonstrates strong anti-estrogenic activity in PDX models of estrogen-receptor positive endocrine-resistant and fulvestrant-resistant breast cancer","volume":"8","author":"Pancholi","year":"2022","journal-title":"NPJ Breast Cancer"},{"issue":"2","key":"10.1016\/j.taap.2026.117969_bb0100","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/19768354.2021.1915380","article-title":"The anti-cancer effect of betulinic acid in U937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis","volume":"25","author":"Park","year":"2021","journal-title":"Anim. Cells Syst. (Seoul)"},{"issue":"1","key":"10.1016\/j.taap.2026.117969_bb0105","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1146\/annurev-med-052423-122001","article-title":"New oral selective estrogen receptor degraders redefine management of estrogen receptor-positive breast cancer","volume":"76","author":"Pathak","year":"2025","journal-title":"Annu. Rev. Med."},{"key":"10.1016\/j.taap.2026.117969_bb0110","doi-asserted-by":"crossref","first-page":"4583","DOI":"10.1210\/en.2002-220369","article-title":"Estrogen receptor \u03b1 and activating protein-1 mediate estrogen responsiveness of the progesterone receptor gene in MCF-7 breast cancer cells","volume":"143","author":"Petz","year":"2002","journal-title":"Endocrinology"},{"issue":"1","key":"10.1016\/j.taap.2026.117969_bb0115","doi-asserted-by":"crossref","first-page":"13748","DOI":"10.1038\/s41598-019-50141-z","article-title":"Role of mitochondria in rescuing glycolytically inhibited subpopulation of triple negative but not hormone-responsive breast cancer cells","volume":"9","author":"Reda","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.taap.2026.117969_bb0120","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.3390\/cells9102261","article-title":"Astrogliosis in an experimental model of hypovitaminosis B12: a cellular basis of neurological disorders due to cobalamin deficiency","volume":"9","author":"Rzepka","year":"2020","journal-title":"Cells"},{"issue":"6","key":"10.1016\/j.taap.2026.117969_bb0125","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.biochi.2011.02.014","article-title":"New betulinic acid derivatives induce potent and selective antiproliferative activity through cell cycle arrest at the S phase and caspase-dependent apoptosis in human cancer cells","volume":"93","author":"Santos","year":"2011","journal-title":"Biochimie"},{"key":"10.1016\/j.taap.2026.117969_bb0130","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0303-7207(02)00415-X","article-title":"Estrogen receptor \u03b1 and Sp1 regulate progesterone receptor gene expression","volume":"201","author":"Schultz","year":"2003","journal-title":"Mol. Cell. Endocrinol."},{"key":"10.1016\/j.taap.2026.117969_bb0135","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2019\/5083158","article-title":"Betulinic acid induces ROS-dependent apoptosis and S-phase arrest by inhibiting the NF-\u03baB pathway in human multiple myeloma","author":"Shen","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"10.1016\/j.taap.2026.117969_bb0140","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/2049-3002-2-17","article-title":"Mitochondrial reactive oxygen species and cancer","volume":"2","author":"Sullivan","year":"2014","journal-title":"Cancer Metab."},{"issue":"1","key":"10.1016\/j.taap.2026.117969_bb0145","doi-asserted-by":"crossref","first-page":"13190","DOI":"10.1038\/s41598-018-31367-9","article-title":"FR58P1a; a new uncoupler of OXPHOS that inhibits migration in triple-negative breast cancer cells via Sirt1\/AMPK\/\u03b21-integrin pathway","volume":"8","author":"Urra","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.taap.2026.117969_bb0150","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2020.604648","article-title":"Betulinic acid inhibits endometriosis through suppression of Estrogen receptor \u03b2 Signaling pathway","volume":"11","author":"Xiang","year":"2020","journal-title":"Front. Endocrinol. (Lausanne)"},{"issue":"6","key":"10.1016\/j.taap.2026.117969_bb0155","first-page":"1669","article-title":"Betulinic acid induces apoptosis by regulating PI3K\/Akt signaling and mitochondrial pathways in human cervical cancer cells","volume":"40","author":"Xu","year":"2017","journal-title":"Int. J. Mol. Med."}],"container-title":["Toxicology and Applied Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26002656?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0041008X26002656?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:26:40Z","timestamp":1787300800000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0041008X26002656"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":31,"alternative-id":["S0041008X26002656"],"URL":"https:\/\/doi.org\/10.1016\/j.taap.2026.117969","relation":{},"ISSN":["0041-008X"],"issn-type":[{"value":"0041-008X","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Mechanistic insights into EB171 anticancer activity in MCF7 and MDA-MB-231 breast cancer cells showing differential responses","name":"articletitle","label":"Article Title"},{"value":"Toxicology and Applied Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.taap.2026.117969","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"117969"}}