Gamze Guney Eskiler*, Gulsah Cecener, Gokhan Dikmen, Unal Egeli and Berrin Tunca Pages 511 - 529 ( 19 )
Objective: In the present work, we report for the first time the therapeutic potential of talazoparib (BMN 673)-SLNs for the treatment of BRCA1 deficient Triple Negative Breast Cancer (TNBC). BMN 673-SLNs were produced by hot-homogenization technique and then characterized.
Methods: The cytotoxic and apoptotic effects of BMN 673-SLNs compared with BMN 673 were determined on HCC1937BRCA1-/-, HCC1937-R resistant TNBC and MCF-10A control cell lines. BMN 673- SLNs were found to have reduced particle size (219.5 ± 1.45 nm) and thus more stable (-28.4 ± 2.52 mV) than BMN 673 (1652 ± 2.46 nm and -18.6 ± 0.45 mV) at 4°C.
Results: In vitro cell line studies demonstrated that BMN 673-SLNs showed significant cytotoxic effects on HCC1937 (29.8%) and HCC1937-R cells (35.7%) at 10 nM for 12 days compared with BMN 673 (HCC1937 cells: 34.0% and HCC1937-R cells: 93.8% at 10 nM for 12 days) (p<0.05). Additionally, BMN 673-SLNs (40.1%) reduced the toxicity of BMN 673 (53.1%) on MCF-10A control cells thanks to unique physical properties.
Conclusion: The apoptotic rates in the 10 nM BMN 673-SLNs treatment (88.78% and 85.56%) for 12 days were significantly higher than those in 10 nM BMN 673 (82.6% and 25.86%) for 12 days in HCC1937 and HCC1937-R cells, respectively (p<0.01). Furthermore, these effects were consistent with the findings of colony formation, wound healing and calcein accumulation analysis. In conclusion, the therapeutic potential of BMN 673-SLNs provides a promising chemotherapeutic strategy for the treatment of drugresistant TNBC.
Triple Negative Breast Cancer (TNBC), PARP inhibitors, Talazoparib (BMN 673), Solid Lipid Nanoparticles (SLNs), Apoptosis, cytotoxic effects.
Deparment of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Deparment of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Central Research Laboratory, Application and Research Center (ARUM), Eskisehir Osmangazi University, Eskisehir, Deparment of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Deparment of Medical Biology, Faculty of Medicine, Uludag University, Bursa