TY  - JOUR
T1  - Inhibition of TNIK with NCB-0846 Reduces Viability and Induces Apoptosis in Triple Negative Breast Cancer Cells
AU  - Harmantepe, Ahmet Tarık
AU  - Dikicier, Enis
AU  - Koçer, Havva Belma
AU  - Kazan, Nur
AU  - Yiğit, Merve
PY  - 2025
DA  - November
Y2  - 2025
DO  - 10.31832/smj.1762998
JF  - Sakarya Tıp Dergisi
PB  - Sakarya Üniversitesi
WT  - DergiPark
SN  - 2146-409X
SP  - 328
EP  - 337
VL  - 15
IS  - 4
LA  - en
AB  - AIM: This study aimed to explore the therapeutic potential of NCB-0846, a TNIK inhibitor targeting the Wnt/β-catenin pathway, on triple-negative breast cancer (TNBC) at the molecular level.MATERIALS AND METHODS: TNBC cell line MDA-MB-231 and non-cancerous breast epithelial cell line MCF-10A were treated with NCB-0846. Cytotoxicity was evaluated using WST-1 assay, apoptosis with Annexin V assay, cell cycle changes with flow cytometry, and morphological alterations with acridine orange staining. RT-PCR was used to assess NCB-0846’s effect on CTNNB1 gene expression.RESULTS: NCB-0846 displayed dose- and time-dependent cytotoxicity in MDA-MB-231 cells, significantly reducing cell viability at 3 μM after 72 hours (p<0.01). Apoptotic cell death was markedly increased at all doses in MDA-MB-231 cells, with notable cell cycle arrest in the G2/M phase (p<0.01). Notably, NCB-0846 induced non-selective toxicity, affecting both cancerous and non-cancerous cells. While CTNNB1 expression decreased in MDA-MB-231 cells, it significantly increased in MCF-10A cells, indicating a potential resistance mechanism in normal breast cells.CONCLUSION: NCB-0846 reduced TNBC cell viability and induced apoptosis via β-catenin inhibition. However, its lack of selective cytotoxicity may limit its use as a monotherapy. Future research could focus on developing combinational strategies to enhance NCB-0846’s specificity for TNBC, improving its therapeutic potential in clinical settings
KW  - Triple negative breast cancer
KW  - Wnt/β-catenin
KW  - TNIK
KW  - NCB-0846
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UR  - https://doi.org/10.31832/smj.1762998
L1  - https://dergipark.org.tr/tr/download/article-file/5145099
ER  -