Triple negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer due to a higher rate of early recurrence, distant metastases and also heterogeneity in the molecular levels. Thus, there is a urgent need for effective therapies. In the recent years, PARP inhibitors have drawn considerable attention for especially BRCA-associated sporadic TNBC patients. In the present study, we aimed to determine the cytotoxic and apoptotic effects of BMN 673, which is a novel and highly potent PARP inhibitor,  on TNBC cell line.

Triple-negative BRCA1-defective HCC1937 breast cancer cell line was treated with BMN673 and the cytoxoxicity effects was evaluated by WST-1 analysis. The apoptotic effects was evaluated using Annexin V-propidium iodide (PI) and cell cycle analysis. The double stained with acridine orange/ethidium bromide of these cells was observed under the fluorescence microscope.

Initial cytotoxicity screening showed that BMN673 displayed the anti-proliferative effect, with in time (6-12 days) and dose-dependent (0.01, 0.1, 1 and 10 nM) (p<0.05). The maximum inhibition rate was measured 19.54%, 24.21%, 49.91%  and 58.0% at 0.01, 0.1, 1 and 10 nM of BMN673 at 12 days, respectively (p<0.05). There was an increase of apoptotic cell death and cell cycle progression in all concentrations compared to the untreated control. Treatment with doses of 0.01, 0.1, 1 and 10 nM BMN673 significantly induced total apoptotic cells (6.2%, 23.45%, 47.95% and 61.28%, respectively) and a significant block at the G₂/M phase. Additionally, we observed a loss of membrane integrity, chromatin condensation and increasing vacuole formation in HCC1937 cells when treated with the maximum concentration of BMN673.

In conlusion, this study has revealed that BMN673 inhibits cell proliferation and  induces cell cycle progression and apoptosis within the minimum concentration. Thus, BMN673 could represent a potentially therapeutic strategy for especially, BRCA-defective TNBC.

Figures:

Fig.1. The Annexin V/PI results of HCC1937 cells treated with the minimum (0.01 nM) and maximum (10 nM) concentration of BMN673 for 12 days compared with control

Fig. 2. The images of HCC1937 cells. (A) Control, (B) Treated with 0.01 nM BMN673, and (C) 10 nM BMN673.

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EMC Abstracts - https://emc-proceedings.com/abstract/a-potential-therapeutic-effects-of-bmn673-a-novel-parp-inhibitor-on-triple-negative-breast-cancer/