in silico and in vitro evaluation of selected herbal compounds as robust her-2 inhibitors for effective treatment of breast cancer

Background and objectives: breast cancer is the most frequently reported malignancy in women worldwide and is a heterogeneous disease. due to different levels of human epidermal growth factor receptor 2 (her-2) and its critical role in tumor progression, her-2 has been considered as a validated target in breast cancer therapy. the present study aimed to identify new and effective her-2 inhibitors from selected plant-based compounds using a computational drug discovery approach. the anticancer effects of top-ranked compounds were then evaluated using cellular and molecular methods. methods: the binding affinities of 47 herbal compounds (including 21 flavonoids, 16 anthraquinones, and 10 cinnamic acids) with the extracellular domain of her-2 were evaluated using m­olecular docking analysis. the top hits were evaluated for their cell proliferation inhibition, apoptosis, and migration effects in high and low her-2-overexpressing skbr-3 and mcf-7 cell lines, respectively. results:  chrysin, chrysophanol, and chlorogenic acid revealed the highest binding affinity to the extracellular domain of her-2; therefore, they were considered the top-ranked her-2 inhibitors in this study. each component inhibited cell proliferation and decreased migration activity of skbr-3 and mcf-7 cell lines, while the skbr-3 cells were affected more. the results of the apoptosis assay showed that chrysin was the only compound that could cause a significant induction of skbr-3 cell apoptosis in comparison to mcf-7 cells. conclusion: the results of the present study suggest that chrysophanol, chlorogenic acid, and especially chrysin may have anticancer effects and could be considered drug candidates for therapeutic aims in human her-2 positive cancer.