Curcumin Analogue EF-24 Induces Ferroptosis in Human Multiple Myeloma Cells MM.1S

Myeloma is a type of malignant tumor that originates from plasma cells.The curcumin analog EF-24 has demonstrated promising antitumor activity.However, its role in myeloma cell proliferation was unclear.In this study, we found that EF-24 could inhibit the proliferation of multiple myeloma cells (MM.1S) by morphological observation and CCK-8 assay.RNA-sequencing analysis indicated that several genes associated with ferroptosis exhibited differential transcription, which was confirmed by RT-qPCR.Therefore, following detection of ferroptosis-related proteins (GPX4 and SLC7A11) and upregulation in the destruction of mitochondrial cristae and other ferroptosis factors, including MDA, GSH, ROS, and Fe 2+ concentrations, were conducted in EF-24-treated MM.1S cells, which concluded that EF-24 could induce ferroptosis in myeloma cells.Conversely, the addition of the ferroptosis inhibitor (ferrostatin-1) could reverse the above changes activated by EF-24.Moreover, NOD/SCID mice grafted with MM.1S cells were constructed, and intravenous injection of EF-24 effectively decreased tumor growth and protected normal tissues, as observed by Hematoxylin-Eosin staining.In summary, our results confirm the EF-24-induced ferroptosis in myeloma cells and exhibited a protective role in model mice grown from implanted MM.1S cells in vivo.