Increasing the Sensitivity of MCF-7 Breast Cancer Cells to Quercetin by Declining DFF45 Expression Level

Abstract

Background and Objectives In recent years, flavonoids such as quercetin have been considered as new anticancer drugs. The mechanisms of action of quercetin include cell cycle arrest, inhabitation of cell proliferation, and induction of apoptosis. This study aims to reduce quercetin’s side effects by increasing MCF-7 breast cancer cells’ sensitivity to this drug and facilitating the cytotoxic effects of quercetin at lower concentrations. Subjects and Methods In this study, the MTT assay was used to determine the concentration that reduced the cell viability by 50% (i.e. lethal concentration 50 or LC50). Then, the expression of the DNA fragmentation factor-45 (DFF45) and some genes in the apoptosis pathway (caspase3, p53, BAX, BCL-2, AIF), the autophagy pathway (LC3, ATG5, Beclin, DRAM) and the AKT/mTOR pathway (AKT1, mTOR, and PTEN), in cells treated with siRNA, quercetin, and quercetin+siRNA using the real-time PCR. Results According to the results of MTT assay, the LC50 value for quercetin was determined 220 μM. The results indicated the initiation of cell death through autophagy pathways. The combined treatment (quercetin+siRNA) increased the mechanism of cancer cell death more than the quercetin treatment alone. Conclusion One of the regulating pathways of apoptosis is forcing the inhibitory effect of DFF45 on DFF40/CAD nuclease. Down regulation of DFF45, along with quercetin administration, can lead to induction of breast cancer cell death which can be a novel technique for the treatment of breast cancer.