Antibiotic-derived approaches in cancer therapy: effectiveness of ikarugamycin in hexokinase-2 inhibition, tissue factor modulation, and metabolic regulation in breast cancer

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dc.contributor.authorAkgül Obeidin, Serra Vildan
dc.contributor.authorŞenol, Maşite Şehadet
dc.contributor.authorDoğru Köseoğlu, Zeynep
dc.contributor.authorBayramoğlu, Feyza
dc.contributor.authorDişli, Sevgi
dc.contributor.authorYiğitbaşı, Türkan
dc.contributor.authorEmekli, Neslin
dc.date.accessioned2026-04-13T13:04:58Z
dc.date.available2026-04-13T13:04:58Z
dc.date.issued2025
dc.departmentİstanbul Medipol Üniversitesi, Sağlık Bilimleri Enstitüsü, Biyokimya Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.description.abstractWe aimed to explore the role of ikarugamycin (IKA) in breast cancer, its connection with hexokinase-2 (HK-2) repression, and tissue factor (TF). This study sought to extend the role of HK-2 as a TF activator in a comprehensive analysis of these interactions from the enzyme, gene, and protein levels. The investigation was performed with MDA-MB-231 and MCF-7 breast cancer lines. The oxidative stress index (OSI), lactate production, and HK activity were assessed using colorimetric assays. Western blot and quantitative PCR analyses were performed to determine HK-2 and TF expressions. Prothrombin time Tests additionally assessed the effect of IKA therapy on TF activation. Three over four significantly downregulated genes were identified after a specific analysis of the IKA’s effect on HK-2 and TF in breast cancer cell lines. In the IKA treatment group, lactate production was markedly reduced (P < 0.05) and hexokinase activity was found to be reduced in all groups (P < 0.05, <0.01). Paclitaxel cytotoxicity independently causes lower OSI in all IKA-treated groups as compared to controls even though OSI is elevated in IKA groups compared to control. Molecular analysis results demonstrated significantly downregulated HK-2 and TF expressions at the protein level (P < 0.05, P < 0.01). Partial thromboplastin time results also showed that IKA-treated cells had longer TF activation duration. A potential indirect association of HK-2 inhibition and TF regulation in breast cancer cells is put forward in this study by presenting IKA’s bioactivation of breast cancer in all gene, protein, and enzyme levels.
dc.description.sponsorshipS. Vildan Akgul Obeidin
dc.identifier.citationAkgül Obeidin, S. V., Şenol, M. Ş., Doğru Köseoğlu, Z., Bayramoğlu, F., Dişli, S., Yiğitbaşı, T. ... Emekli, N. (2025). Antibiotic-derived approaches in cancer therapy: effectiveness of ikarugamycin in hexokinase-2 inhibition, tissue factor modulation, and metabolic regulation in breast cancer. Anti-Cancer Drugs, 36(4), 328-337. http://dx.doi.org/10.1097/CAD.0000000000001689
dc.identifier.doi10.1097/CAD.0000000000001689
dc.identifier.endpage337
dc.identifier.issn0959-4973
dc.identifier.issn1473-5741
dc.identifier.issue4
dc.identifier.pmid39879102
dc.identifier.scopus2-s2.0-85217138801
dc.identifier.scopusqualityQ2
dc.identifier.startpage328
dc.identifier.urihttp://dx.doi.org/10.1097/CAD.0000000000001689
dc.identifier.urihttps://hdl.handle.net/20.500.12511/13420
dc.identifier.volume36
dc.identifier.wosWOS:001439236900008
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorAkgül Obeidin, Serra Vildan
dc.institutionauthorŞenol, Maşite Şehadet
dc.institutionauthorDoğru Köseoğlu, Zeynep
dc.institutionauthorBayramoğlu, Feyza
dc.institutionauthorYiğitbaşı, Türkan
dc.institutionauthorEmekli, Neslin
dc.institutionauthorid0000-0002-0757-9743
dc.institutionauthorid0000-0002-0675-1839
dc.institutionauthorid0000-0002-0109-5086
dc.language.isoen
dc.relation.ispartofAnti-Cancer Drugs
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAnticancer Antibiotics
dc.subjectBreast Cancer
dc.subjectCancer Metabolism
dc.subjectHexokinase-2
dc.subjectTissue Factor
dc.titleAntibiotic-derived approaches in cancer therapy: effectiveness of ikarugamycin in hexokinase-2 inhibition, tissue factor modulation, and metabolic regulation in breast cancer
dc.typeArticle

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