Determination Of Selective Cytotoxicity From Ncb-0846 In The Treatment Of Triple Negative Breast Cancer

BACKGROUND It was aimed to investigate the therapeutic effect of NCB-0846 inhibition of TNIK, which is the activator kinase of Wnt/β-catenin signaling pathway, on triple negative breast cancer at the molecular stage. METHODS MDA-MB-231 cells were used as triple negative breast cancer cell line and MCF-10A cells were used as control cell line. WST-1 analysis showed the cytotoxic effect of NCB-0846, Annexin V analysis showed its apoptotic effect, cell cycle analysis showed its effect on cell cycle, and Acridine Orange staining showed its effect on cell morphology. In addition, the effect of NCB-0846 on CTNNB1 (β-catenin) gene expression was demonstrated by RT-PCR analysis. RESULTS The viability rates in NCB-0846, MDA-MB-231 cells decreased significantly in a time and dose dependent manner (p < 0.01). The lowest viability rates for MDA-MB-231 cells were determined as 42,20% at the 3 µM dose after 72 hours of incubation. After 72 hours of incubation in MCF-10A cells, the viability rate was determined as 53,92% at 3 µM dose (p < 0.01). Apoptotic cell rates were determined as 60,5% and 39,33% for 3 µM NCB-0846 incubation in MDA-MB-231 and MCF-10A cells, respectively. In the RT-PCR analysis, while the expression level of CTNNB1 was decreased in MDA-MB-231 cells, it was determined that it increased significantly in MCF-10A cells. CONCLUSION NCB-0846 was shown to induce apoptosis while inhibiting viability in MDA-MB-231 cells. Our results suggest that NCB-0846 may be a suitable candidate for cancer therapy, but further in vitro and in vivo studies are required to better understand its mechanisms of action.