Pomalidomide Induces Myeloma Cell Death Via GPX4-Mediated Ferroptosis

Pomalidomide is one of the immunomodulatory drugs (IMiDs) used for multiple myeloma (MM) treatment. However, the exact molecular mechanism of pomalidomide in MM therapy remains unclear. The current study demonstrated that pomalidomide treatment inhibited MM cell proliferation and induced cell death via ferroptosis. This phenomenon could be reversed by ferrostatin-1, a ferroptosis inhibitor. Additionally, pomalidomide induced ferroptosis by increasing lipid peroxidation, reactive oxygen species (ROS), malondialdehyde (MDA), and 4-hydroxynonenal (4-HNE) expression. Furthermore, it blocked the conversion of GSH to GSSG and inhibited glutathione hydroperoxidase 4 (GPX4) expression. In vivo experiments demonstrated that pomalidomide significantly reduced the growth of subcutaneous MM tumors in mice, as evidenced by decreased tumor weight and volume. The molecular mechanisms observed in the mice model corroborated the findings from in vitro experiments. Collectively, these results enhance our understanding of the potential mechanisms of pomalidomide in MM therapy.

No relevant conflicts of interest to declare.