Astragaloside IV suppresses triple‑negative breast cancer cell migration and invasion by targeting BCAT1‑mediated branched‑chain amino acid metabolism

Branched‑chain amino acid (BCAA) transaminase 1 (BCAT1), the rate‑limiting enzyme in BCAA metabolism, serves a pivotal role in tumor progression. Astragaloside IV (AS‑Ⅳ) exhibits potential antitumor properties; however, whether AS‑IV suppresses breast cancer migration by modulating BCAA metabolism via BCAT1 remains to be elucidated. The present study aimed to investigate whether AS‑IV inhibits the invasion and migration of MDA‑MB‑231 triple‑negative breast cancer (TNBC) cells by targeting BCAT1‑mediated BCAA metabolic reprogramming. The present study used network pharmacology to predict AS‑IV targets against breast cancer invasion, followed by BCAT1 knockdown and overexpression in MDA‑MB‑231 cells. Using molecular docking, cellular thermal shift assay, wound healing, Transwell, western blotting, quantitative PCR and liquid chromatography‑mass spectrometry metabolomics, the present study systematically evaluated: i) AS‑IV‑BCAT1 direct binding and protein stability; ii) BCAA metabolic flux regulation via the branched‑chain α‑ketoacid dehydrogenase kinase (BCKDK)/branched‑chain α‑ketoacid dehydrogenase (BCKDH) axis; and iii) functional impacts on breast cancer cell migration and invasion. Network pharmacology predicted BCAT1 as a key potential target of AS‑IV, with significant enrichment of the BCAA metabolic pathway. The results of the present study suggested that AS‑IV binds to and stabilizes BCAT1 in vitro, an effect that is associated with reduced migration and invasion of MDA‑MB‑231 cells. It also promotes BCAA degradation via the BCKDK/BCKDH axis, lowering intracellular BCAA levels and suppressing malignancy. Notably, AS‑IV maintained dose‑dependent inhibition even with BCAT1 knockdown or overexpression, albeit with reduced efficacy. In conclusion, the present study suggested that AS‑IV suppresses MDA‑MB‑231 cell invasion and migration by targeting BCAT1‑mediated BCAA metabolism. These findings support further evaluation of AS‑IV in TNBC and highlight BCAA metabolism as a potential intervention point in future research.