A novel chrysin derivative HYS-072 induces apoptosis and autophagy in Triple-negative breast cancer cells.

Abstract

Triple-negative breast cancer (TNBC) poses a significant threat to women's health as a malignant breast tumour. The limited efficacy of chemotherapy has spurred the exploration of alternative therapeutic strategies. Natural products serve as the foundation for drug discovery, with structural alterations playing a crucial role in the process of pharmaceutical exploration. This study introduced a new chrysin derivative, HYS-072, which includes a urea group and demonstrates micromolar equipotent inhibition of MDA-MB-231 cells (IC₅₀ = 3.3 μM). In vitro investigations have shown that HYS-072 triggers apoptosis and autophagy in MDA-MB-231 cells by modulating the PI3K/AKT/mTOR signalling pathway. In the xenograft model conducted in vivo, HYS-072 demonstrated efficacy in suppressing cancer growth through the modulation of autophagy-related signalling pathways. Collectively, HYS-072 shows promise as a potential therapeutic agent for TNBC. This research underscores the potential of utilising natural product-based autophagy induction as a strategy for TNBC treatment.