CCB-4 and its sugar complexes induce mitotic catastrophe and p53-independent apoptosis through caspase-2 elevation and suppression of c-Myc in T47D cells

Adding boron to curcumin analogs enhances their ability to inhibit cell growth and facilitates their detection within cells. Derivatives of diboronocurcumin are, therefore, promising options for cancer treatment. Our previous in silico analysis revealed that CCB-4 binds more tightly to proteins associated with breast cancer than Pentagamaboronon-0. We created sugar complexes of CCB-4 using fructose (CCB-4 Fr) and sorbitol (CCB-4 So) to enhance solubility and cellular uptake. This research aimed to assess the cytotoxic activity and anticancer potential of CCB-4, CCB-4 So, and CCB-4 Fr against T47D breast cancer cells (ER+, PR+, p53 mutant). We investigated the expression of phosphorylated epidermal growth factor receptor (p-EGFR), c-Myc, HDAC1, and caspase-2 by capillary Western blot analysis, including cytotoxicity using MTT assay, clonogenic survival, cell cycle progression, and apoptosis. CCB-4, CCB-4 So, and CCB-4 Fr demonstrated strong cytotoxic effects and had IC 50 values of 8, 6, and 5 μM, respectively. All the substances caused G2/M phase arrest and significantly reduced colony formation, leading to mitotic catastrophe. Mechanistically, treatment reduced p-EGFR, c-Myc, and HDAC1 expressions and activated apoptosis through caspase-2 independently of p53. These findings suggest that CCB-4 and its sugar complexes have promising anticancer effects against luminal A breast cancer cells by triggering caspase-2-mediated apoptosis and mitotic catastrophe.