Abstract
Breast cancer is a major cause of morbidity in women worldwide, thus necessitating the identification of novel therapeutic options. The present study aimed to investigate the inhibitory effects of a crude flavonoid extract (CFENS) isolated from the medicinal herb Nigella sativa on the proliferation of MCF-7 human breast cancer cells and to elucidate the mechanism of action. The MCF-7 cell viability was examined by an MTT assay. Fluorescent microscopy, flow cytometry analyses, and agarose gel electrophoresis were carried out to assess the pro-apoptotic potentiality of CFENS. Western blot analyses were done to detect gene expression. The findings showed that CFENS dose-dependently inhibited proliferation and induced apoptosis in MCF-7 cells. Typical morphologic and biochemical changes of apoptosis, including cell shrinkage and detachment, nuclear condensation, and DNA damage, were observed after the CFENS treatments. CFENS triggered ROS accumulation, GSH depletion, disruption of mitochondrial membrane potential, activation of caspases-3/7 and -9, and an increase in the Bax/Bcl-2 ratio in MCF-7 cells. In addition, CFENS induced cell cycle arrest, upregulated the expression levels of p53 and p21 proteins, and downregulated the expression of cyclin D1. These findings indicate that CFENS may help prevent breast cancer and may potentially be a useful agent for the treatment of certain malignancies.