Hydrastinine and β-sitosterol Synergistically Target Acute Myelocytic Leukemia in a Ferroptosis-Related Prognostic Model

Abstract

Abstract Acute myeloid leukemia (AML) is a malignant tumor with a high incidence and poor prognosis. Ferroptosis plays a crucial role in regulating carcinogenesis and tumor progression. However, a combination therapy of traditional Chinese medicine and western medicine targeting AML using a ferroptosis-related prognostic model is lacking. Herein, β-sitosterol and hydrastinine were shown to exert a significant synergistic effect on AML. First, prognostic genes associated with ferroptosis were evaluated and the prognosis model was obtained by bioinformatics. Second, the results of immune infiltration analysis showed that the abundances of B cells, macrophages, T cells and monocytes were significantly different between the high- and low-risk groups. Notably, these genes were associated with 296 drugs in the CellMiner database. Network pharmacology and molecular docking analyses showed that β-sitosterol, the active ingredient in Tripterygium wilfordii, targeted oncogenes, CAS9 and PON1. Combinatorial experiments further supported that hydrastinine and β-sitosterol significantly inhibited the growth of AML cells and improved the drug sensitivity of AML cells to ferroptosis inducers. In conclusion, our findings provide a potential strategy for the combined treatment of AML for integrative medicine.