Sodium New Houttuyfonate Induces Apoptosis of Breast Cancer Cells via ROS/PDK1/AKT/GSK3β Axis

SIMPLE SUMMARY: Breast cancer treatment has long been a problem plaguing women’s health. In order to explore whether sodium new houttuyfonate (SNH) has a potential therapeutic effect on breast cancer, this study jointly demonstrated that SNH has a significant apoptotic effect on breast cancer through biogenic analysis and research trials. This effect is achieved by promoting the excessive accumulation of reactive oxygen species (ROS), inducing mitochondrial damage, regulating the aggregation of apoptotic proteins near mitochondria, and targeting the PDK1-AKT-GSK3β pathway. This study demonstrated the potential therapeutic effect of SNH and provided a reference for the application of SNH in breast cancer. ABSTRACT: Background: Sodium new houttuyfonate (SNH) has been reported to have anti-inflammatory, anti-fungal, and anti-cancer effects. However, few studies have investigated the effect of SNH on breast cancer. The aim of this study was to investigate whether SNH has therapeutic potential for targeting breast cancer. Methods: Immunohistochemistry and Western blot analysis were used to examine the expression of proteins, flow cytometry was used to detect cell apoptosis and ROS levels, and transmission electron microscopy was used to observe mitochondria. Results: Differentially expressed genes (DEGs) between breast cancer-related gene expression profiles (GSE139038 and GSE109169) from GEO DataSets were mainly involved in the immune signaling pathway and the apoptotic signaling pathway. According to in vitro experiments, SNH significantly inhibited the proliferation, migration, and invasiveness of MCF-7 (human cells) and CMT-1211 (canine cells) and promoted apoptosis. To explore the reason for the above cellular changes, it was found that SNH induced the excessive production of ROS, resulting in mitochondrial impairment, and then promoted apoptosis by inhibiting the activation of the PDK1-AKT-GSK3β pathway. Tumor growth, as well as lung and liver metastases, were suppressed under SNH treatment in a mouse breast tumor model. Conclusions: SNH significantly inhibited the proliferation and invasiveness of breast cancer cells and may have significant therapeutic potential in breast cancer.