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.