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. K E Y W O R D S apoptotic death, BMN 673 (talozoparib), BRCA, triple negative breast cancer J Biochem Mol Toxicol. 2019;33:e22286. wileyonlinelibrary.com/journal/jbt Abbreviations: dsDNAs, DNA double-strand breaks; HR, homologous recombination; PARP, poly ADP ribose polymerase; TN, triple negative; TNBC, triple negative breast cancer.
SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section at the end of the article.