BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile
JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.33, sa.5, 2019 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 33 Sayı: 5
- Basım Tarihi: 2019
- Doi Numarası: 10.1002/jbt.22286
- Dergi Adı: JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Anahtar Kelimeler: apoptotic death, BMN 673 (talozoparib), BRCA, triple negative breast cancer, SYNTHETIC LETHALITY, VIVO SENSITIVITY, DNA-REPAIR, CELL-LINES, MECHANISMS, BRCA1
- Bursa Uludağ Üniversitesi Adresli: Evet
Özet
The objective of the present study was to elucidate the effect of BMN 673 (talozoparib) on BRCA1 mutant (HCC1937) and wild-type (MDA-MB-231) triple negative breast cancer (TNBC). The in vitro cytotoxicity results indicated that BMN 673 had considerable inhibitory effects on HCC1937 and MDA-MB-231 cell lines by inducing apoptosis, multicaspase activity, G2/M arrest, and altering the expression levels of apoptosis-related genes (P < 0.01). Additionally, BMN 673 indicated no toxicity on MCF-10A control cells until a certain concentration and incubation time. However, BMN 673, a novel and selective poly ADP ribose polymerase inhibitor, was more potent in TNBC cells bearing BRCA1 mutant than those with wild-type BRCA1. In conclusion, our study, for the first time, demonstrated a molecular mechanism of the induction of apoptosis by BMN 673 in TNBC with different genetic profile. However, further investigations regarding the exact molecular mechanisms underlying BMN 673-inducing apoptotic death and gene-cell line associations are required.