BMN 673 (talazoparib): A potent PARP inhibitor for triple negative breast cancer with different genetic profile

Eskiler G. G., ÇEÇENER G., EGELİ Ü., TUNCA B.

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, cilt.33, sa.5, 2019 (SCI-Expanded) identifier identifier identifier

  • 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.