Reversal effect of quercetin on talazoparib resistance in BRCA1 mutant triple negative breast cancer

Authors : Gamze GÜNEY ESKİLER, Gülşah ÇEÇENER, Ünal EGELİ, Berrin TUNCA

Pages : 19-25

Doi:10.18621/eurj.454176

View : 22 | Download : 7

Publication Date : 2020-01-04

Article Type : Research Paper

Abstract :Objectives: Polyinsert ignore into journalissuearticles values(ADP-ribose); polymerase insert ignore into journalissuearticles values(PARP); inhibitors have demonstrated an outstanding activity in patients with BRCA -mutated and wild-type breast cancer. However, the identification of resistance mechanisms to PARP inhibitors is a significant clinical challenge in effective treatment. Thus, new therapeutic strategies are urgently needed to overcome resistance. The aim of the current study was to explore the potential effect of quercetin on HCC1937 insert ignore into journalissuearticles values( BRCA1 mutant); and talazoparib insert ignore into journalissuearticles values(BMN 673);, a PARP inhibitor, resistant HCC1937 insert ignore into journalissuearticles values(HCC1937-R); triple negative breast cancer cells insert ignore into journalissuearticles values(TNBC);. Methods: We firstly generated BMN 673 resistance HCC1937 cells by continuous exposure to BMN 673 during 6 months. Then, cells were exposed to the different concentration insert ignore into journalissuearticles values(0-100 µM); of quercetin and the cytotoxic and apoptotic effects of quercetin on these cells were evaluated by WST-1, Annexin V and dual acridine orange-ethidiumbromide insert ignore into journalissuearticles values(Et-BR); staining. Results: The cell viability of HCC1937 and HCC1937-R cells reduced to 37.1% and 44.2% at a concentration of 100 μM, respectively for 48 h insert ignore into journalissuearticles values( p < 0.01);. Apoptotic rates of HCC1937 and HCC1937-R cells treated with 100 μM quercetin were nearly 56.0% and 46.0%, respectively insert ignore into journalissuearticles values( p < 0.01);. Additionally, the apoptotic morphologicalchanges were observed in these cells. Conclusions: In conclusion, the obtained results suggest that quercetin could potentially be used as an alternative therapeutic strategy in BRCA1 mutant TNBC to overcome acquired BMN 673-resistance. 
Keywords : Triple negative breast cancer, PARP inhibitors, talazoparib BMN 673, quercetin, apoptosis, BRCA1