Agaricus blazei Murill Extract (FA-2-b-β) Induces Ferroptosis in Diffuse Large B-Cell Lymphoma via the Nrf2/Ho-1 Pathway.

Introduction: Ferroptosis is a recently identified iron-dependent programmed cell death closely linked to the progression of diffuse large B-cell lymphoma (DLBCL). While studies have shown that FA-2-b-β extracted from Agaricus blazei Murill affects various malignancies, its specific role in modulating ferroptosis in DLBCL and the underlying mechanisms are not yet clear.

Objectives: This study aims to elucidate the anticancer properties and mechanisms of FA-2-b-β in inducing ferroptosis in DLBCL cells.

Methods: The cell counting kit 8 assay was carried out to evaluate the inhibition of cellular proliferation. Ferroptosis was evaluated using the ferrous colorimetric method, together with kits for measuring malondialdehyde (MDA), reduced glutathione (GSH), reactive oxygen species (ROS), western blotting, JC-1 assays, and transmission electron microscopy. Reverse transcriptionquantitative polymerase chain reaction and western blot were conducted to determine whether FA- 2-b-β affected nuclear factor erythroid 2- related factor 2 (Nrf2) and heme oxygenase 1 (HO-1).

Results: FA-2-b-β induced ferroptosis in DLBCL cells by elevating the ROS and MDA levels, facilitating the accretion of Fe²⁺, diminishing GSH, upregulating the expression of PTGS2, and downregulating the expression of FTH1, SLC7A11, and GPX4. Furthermore, FA-2-b-β caused structural damage to mitochondria and diminished the mitochondrial membrane potential. The ferroptosis triggered by FA-2-b-β also led to the downregulation of Nrf2 and HO-1, thereby regulating the Nrf2/HO-1 pathway.

Conclusion: FA-2-b-β suppressed DLBCL cell growth by inducing ferroptosis through the Nrf2/HO-1 pathway, making it an attractive potential therapeutic option.