Hard antler extract inhibits invasion and epithelial–mesenchymal transition of triple-negative and Her-2+ breast cancer cells by attenuating nuclear factor-κB signaling

Abstract

Ethnopharmacological relevanceHard antler extract (HAE) is a traditional Chinese medicine and has potent antitumor, antioxidative, anti-inflammatory, and immunomodulatory activities. Previous studies have demonstrated that HAE can inhibit human prostate cancer metastasis and murine breast cancer proliferation. However, the effect of HAE on human breast cancer cells has not been clarified.Aim of the study: To investigate the effects and underlying mechanism of HAE on self-renewal of stem-like cells and spontaneous and transforming growth factor (TGF)-β1-enhanced wound healing, invasion and epithelial–mesenchymal transition (EMT) in breast cancer cells. MethodsHAE was prepared from sika deer by sequential enzymatic digestions and the active compounds were determined by HPLC. The effects of HAE on the viability, mammosphere formation, wound healing and invasion of MDA-MB-231 and SK-BR3 cells were determined. The impact of HAE treatment on spontaneous and TGF-β1-promoted EMT and the nuclear factor (NF)-κB signaling in breast cancer cells was examined by quantitative RT-PCR and western blotting. ResultsTreatment with HAE at varying concentrations did not change the viability of breast cancer cells. However, HAE at 0.25 or 0.5 mg/mL significantly reduced the number and size of formed mammospheres, and inhibited spontaneous and TGF-β1-enhanced wound healing, invasion and EMT in MDA-MB-231 and SK-BR3 cells in a dose-dependent manner. TGF-β1 treatment significantly decreased IκBα expression and increased NF-kBp65 phosphorylation in breast cancer cells, indicating that TGF-β1 enhanced NF-κB signaling. In contrast, HAE treatment attenuated the spontaneous and TGF-β1-enhanced NF-κB signaling in breast cancer cells. ConclusionOur data indicated that HAE inhibited the self-renewal of stem-like cells and spontaneous and TGF-β1-enhanced wound healing, invasion and EMT in breast cancer cells by attenuating the NF-κB signaling in vitro.