The Combined Therapeutic Effect of Capecitabine and Naringin on HER2+ (SK-BR-3) and HER2- (MCF-7) Human Breast Cancer Cells Lines

Abstract Breast cancer is one of the most common cancers among women. The use of natural products to improve the effectiveness of chemotherapy drugs against the proliferation of cancer cells is increasing. Here, we hypothesized that naringin in combination with capecitabine may have a synergistic effect on inhibiting proliferation and inducing apoptosis in MCF-7 and SK-BR-3 breast cancer cell lines. MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) was performed to study the effect of drugs alone and in combination on the cytotoxicity of cell lines and to determine IC50 and Combination Index (CI). Moreover, the expression of Bax and Bcl-2 and caspase3 apoptotic markers were measured by Real-Time PCR after treatment. The MTT results showed that the IC50 of naringin and capecitabine in the MCF-7 cell line was 58 µg ml− 1 and 619.36 µg ml− 1, respectively, and the IC50 of these compounds for the SK-BR-3 cell line was 56.65 µg ml− 1 and 679.51 µg ml− 1. The combined use of naringin and capecitabine led to a significant decrease in the IC50 of these compounds, and the CI values were less than 1, which indicates the synergistic effects of these compounds. The gene expression results also showed an increase in the ratio of Bax/Bcl-2 by naringin-capecitabine compared with capecitabine in both cell lines. Naringin-capecitabine-induced cell death was probably controlled by caspase-3 and Bax/Bcl-2-dependent apoptosis. Also, the combination of naringin-capecitabine has more antiproliferative properties on HER2+ cells compared with HER2−.