Reprogramming SREBP1-dependent lipogenesis and inflammation in high-risk breast with licochalcone A: a novel path to cancer prevention

This study investigates the effects of Licochalcone A (LicA) on protein stability in breast cancer cells using Proteome Integral Solubility Alterations (PISA) proteomics. We treated MCF-7 (ER+) and MDA-MB-231 (ER-) cells with LicA (10 µM) for 24 hours and subjected them to temperature-dependent protein solubility profiling. Thermal denaturation assays (40-65°C) followed by LC-MS/MS analysis with TMT labeling were performed to identify differentially stabilized and destabilized proteins. Our results indicate that LicA significantly destabilizes proteins involved in SREBP1-dependent lipogenesis, PI3K-AKT signaling, and NF-kB-mediated inflammation, while stabilizing pathways associated with antioxidant defense and metabolic reprogramming. These findings suggest a mechanism by which LicA alters the breast cancer proteome, leading to reduced tumor proliferation.