Objective: Breast cancer (BC) is one of the most commonly diagnosed malignancies among females all over the world.The use of natural and complementary compounds is a new option in chemotherapy. The aim of the present study was to investigate the synergic effect of Quercetin (QUR) and Raloxifene (RAL) on BC cell lines in vitro.

Materials and Methods: The cell lines (MCF-7 and MDA-MB-231) were treated with QUR (0, 25 50, 100, 150, 200 µM), and RAL (1 µM) alone, and in combination. Cell viability was evaluated using the MTT assay. Ferric reducing antioxidant power (FRAP) and Griess method were used to measure total antioxidant capacity (TAC) and NO level of biological samples respectively. Changes in the expression of apoptotic-related genes were detected using real-time PCR.

Results: QUR (100, 150 and 200 µM) decreased cell viability significantly in MDA231 and MCF7 cells (p<0.01). Furthermore, Ral (1 µM) showed a significant decrease in both cell types (p<0.01). The synergistic effect of QUR (150) and RAL was also greater in MDA231 cells. NO levels in QUR, Ral, and synergic groups increased significantly in both cell lines (p<0.001). In treated groups, QUR and RAL significantly decreased cell migration, MMP2 and MMP9 expression, and increased apoptotic genes expression significantly (p<0.001). QUR increased TAC in both BC cell lines (p<0.00) while it was decreased by RAL. Synergic groups increased TAC in BC cells significantly (p<0.001).

Conclusions: QUR and RAL show synergistic anti-cancer effects on cell viability, NO production, cell migration, and apoptotic genes. QUR as a supplement can potentiate the anti-cancer effects of RAL in BC.