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, vol.33, no.5, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 33 Issue: 5
  • Publication Date: 2019
  • Doi Number: 10.1002/jbt.22286
  • Title of Journal : JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY

Abstract

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.