The Effect of PJ-34 and Ionizing Radiation on Viability of MDA-MB-231 Human Triple Negative Breast Cancer Cell Line

Abstract

Background and Objectives Radiation therapy plays an important role in the treatment of breast cancer but sometimes its effect is limited by the radioresistance of cancer cells. Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in many cellular processes, especially, DNA repair. Various PARP inhibitors have been demonstrated to exhibit anti cancer activity as a single agent and in combination with chemotherapeutic agents or radiation therapy. PJ-34, one of the PARP inhibitors, has been shown to sensitize other types of tumor to chemotherapy and radiotherapy. However, the analysis has never been done on MDA-MB-231 human triple negative breast cancer cells in combination with ionizing radiation. Thus, the aim of the study was to analyze the combined effect of PJ-34 and ionizing radiation on proliferation of MDA-MB-231 cells. Material and Method Human triple negative breast cancer cell line MDA-MB-231 was used for the study. Cells were grown as monolayers in Dulbecco’s Modified Eagle’s medium (DMEM; Sigma-Aldrich) supplemented with 10% fetal bovine serum (Gibco), 100 U/mL penicillin with 100 µg/mL streptomycin (Gibco) and 2 mM L-glutamine (Gibco) at 37°C in humidified 5% CO2. PJ-34 solution was purchased from SigmaAldrich, and frozen at −80°C in small quantities to prevent freeze-thaw cycles. Working solutions were prepared before each experiment. Cells were treated with different concentrations of PJ-34 one hour before irradiation. Cell irradiations were performed with the single dose of 1, 2, and 4 Gy, using a medical Clinac 2100C/D linear accelerator. Cells were irradiated with the drug present in the medium and were immediately returned to the incubator. The effect on MDA-MB-231 breast cancer cells was evaluated by MTT (3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) cell proliferation assay 71 hours after the irradiation. Results We examined the effect of PARP in[...].