BIOACTIVITY OF HEXOKINASE II INHIBITOR IKARUGAMYCIN AND RELATION WITH TISSUE FACTOR IN BREAST CANCER CELL LINES

VİLDAN AKGUL OBEIDIN, FEYZA BAYRAMOGLU, SEVGİ DISLI, NESLİN EMEKLI

Acta Pharmaceutica Sciencia - 2025;63(1):192-208

Istanbul Medipol University, Faculty of Medicine, Department of Biochemistry, Istanbul, Türkiye

 

Despite the understanding gained from scientific studies regarding Hexokinase II (HK2)’s involvement in cancer cell metabolism, there are no reports of directly inhibiting HK-2 enzyme to affect tissue factor (TF) activity in cancer cells. This study primarily investigates the complex mechanisms triggering neoplastic cell formation by examining the in vitro bioactivation of the Ikarugamycin (IKA) molecule, commonly used as an antibiotic. The IC50 values for MDA-MB-231 (TNBC) and MCF-7 (TPBC) cell lines are 24.1 µM and 19.25 µM, respectively. Furthermore, TF activation in breast cancer cell lines was demonstrated through Prothrombin Time (PT) analysis, showing that IKA effectively prolongs TF activation compared to Sodium Oxamate and Paclitaxel (Ptx), commonly used as a chemotherapeutic agent. Additionally, it was observed to be more effective in hormone-dependent MCF-7 breast cancer cell lines. Future studies should focus on investigating the changes in protein, enzyme, and gene levels of TF following treatment with IKA.