Calycosin Induces Ferroptosis by SLC7A11 Through the PI3K/Akt Pathway in Acute Myelocytic Leukemia

Acute myelocytic leukemia seriously impairs the health and lifespan of patients; thus, effective treatment methods for acute myelocytic leukemia need to be urgently determined. This study aimed to investigate the role of calycosin in acute myelocytic leukemia and elucidate its mechanism of action. Cells were treated with calycosin and then subjected to cell counting Kit-8, flow cytometry, and western blot assays to detect cell viability, cells apoptosis, and apoptosis-related proteins, respectively. To demonstrate that calycosin induces ferroptosis in acute myelocytic leukemia cells, the levels of iron ion, lipid- reactive oxygen species (ROS), cysteine, glutathione, and glutathione peroxidase 4 were measured using corresponding kits. The ferroptosis-related genes Ptgs2 and Chac1 were detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The solute carrier family 7a member 11 (SLC7A11) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B signaling pathways were analyzed by western blotting. We found that calycosin inhibited cell viability and increased the level of apoptosis in acute myelocytic leuke cells. It also increased the iron ion levels, accompanied by an increase in lipid ROS levels, and increased the expression of ferroptosis-related genes. In contrast, cysteine, glutathione, and glutathione peroxidase 4 expressions, as well as SLC7A11 expression, were decreased by calycosin. Calycosin inhibited PI36/AKT signaling in a dose-dependent manner. However, these effects were reversed by SLC7A11 overexpression. Thus, calycosin can alleviate acute myelocytic leukemia and may be a novel treatment strategy for patients with acute myelocytic leukemia.