Kaempferitrin's Dual Assault: Inducing Apoptosis and Ferroptosis in Diffuse Large B-Cell Lymphoma via NF-κB Inactivation.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and is an aggressive and highly heterogeneous tumor. Kaempferitrin (KPF) is a natural flavonoid glycoside that exerts a protective role in multiple human tumors. However, the impact of KPF on DLBCL remains unclear. In this study, we discovered that 240 μM KPF had a toxic effect on GM12878 cells. KPF inhibited DLBCL cell proliferation while promoting apoptosis in these cells. Additionally, KPF induced ferroptosis in DLBCL cells by elevating intracellular Fe²⁺ levels and reactive oxygen species (ROS) levels, alongside reducing the protein levels of GPX4 and SLC7A11. Moreover, KPF suppressed the activation of NF-κB in DLBCL cells. Building upon this finding, we further validated that KPF reduced DLBCL cell malignant growth through the inhibition of NF-κB activation. Meanwhile, animal studies further suggested that KPF inhibited DLBCL proliferation in vivo, mainly through reduced subcutaneous tumor volume, tumor weight, and increased apoptosis levels in mice. Furthermore, KPF suppressed the disorder of DLBCL cancer tissue arrangement and decreased p-NF-κB and p-IKB-α protein levels in DLBCL subcutaneous tumor tissues. In summary, our findings suggested that KPF enhanced apoptosis and ferroptosis in DLBCL cells via the deactivation of the NF-κB signaling pathway.