Induction of Cuproptosis by Dichloromethane Extract From <i>Patrinia scabiosaefolia</i> Fisch on <scp>K562</scp> Cells

Cuproptosis is a newly identified form of cell death that relies on copper (Cu) ionophores to transport Cu into cancer cells. As a perennial herb, Patrinia scabiosaefolia Fisch (PS) has garnered significant attention owing to its analgesic, anti-inflammatory, antibacterial, and antitumor properties. Previous research has shown that the extract from PS (DEPS) can inhibit the growth of leukemia cell lines. However, the specific mechanism of its anti-leukemic effect has not been fully clarified. Therefore, this study was conducted to investigate the molecular mechanism of cuproptosis in the treatment of leukemia with DEPS. Our results demonstrated that DEPS up-regulated SLC31A1 and down-regulated ATP7B expression, which increased intracellular copper concentration, down-regulated FDX1, influenced the lipoylation of DLAT and DLD, and subsequently increased the expression of the stress protein HSP70 and the expression of PDHA1, inducing copper death in K562 cells. In addition, we investigated the toxicity of DEPS in vivo and demonstrated its low in vivo toxicity and adequate in vivo safety. In conclusion, our results suggest that DEPS may induce cuproptosis in cells, offering valuable insights for the future application of PS in leukemia treatment.