Inhibition of TNIK with NCB-0846 Reduces Viability and Induces Apoptosis in Triple Negative Breast Cancer Cells

Yıl 2025, Cilt: 15 Sayı: 4, 328 - 337

Ahmet Tarık Harmantepe , Enis Dikicier , Havva Belma Koçer , Nur Kazan , Merve Yiğit

Öz

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

Anahtar Kelimeler

Triple negative breast cancer , Wnt/β-catenin , TNIK , NCB-0846

Etik Beyan

The study was approved by the Sakarya University Ethics Committee (Date: 29.01.2021, decision no: E. 71522473-050.01.04-606139). The study was carried out following the Helsinki Declaration and international guidelines. This study was conducted in accordance with the principles of the Declaration of Helsinki. Since it was a retrospective study, informed consent/consent form was not obtained from the patient/relatives.

Destekleyen Kurum

This study was funded by a grant from the Scientific Research Projects Foundation (BAP) of the Sakarya University of Turkey [Project No: 2021-7-25-9].

Proje Numarası

Project No: 2021-7-25-9

Teşekkür

I would like to extend my sincere thanks to Gamze Guney Eskiler

Kaynakça

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