COTI-2 reactivates mutant p53 and inhibits growth of triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) currently lacks an approved targeted therapy. The tumour suppressor TP53 gene is mutated in approximately 80% of TNBC cases. COTI-2 is a third-generation thiosemicarbazone engineered for high efficacy and low toxicity which acts by reactivating mutant p53 to a WT form. The aim of this study was to investigate COTI-2 as a targeted therapy for TNBC patients. Using a panel of 18 breast cell lines, we carried out MTT assay. p53 protein folding was determined by immunofluorescent staining with the p53 mutant-specific antibody PAb240 and the p53 WT-specific PAb1620. Surface plasmon resonance was used to determine binding affinity of COTI-2 to full length (FL) p53, and the DNA-binding domain (DBD). Flow cytometry was used to measure apoptosis. TNBC cell lines were significantly more responsive to COTI-2 than non-TNBC cell lines (p = 0.04). Furthermore, lower IC We conclude that targeting mutant p53 with COTI-2 is a potential approach for treating p53-mutated TNBC.