Mechanistic Insights into the Antiproliferative Effect of Redox-active Iron Chelator Dp44mT on Multiple Myeloma Cell Lines

ABSTRACT: Impaired iron metabolism has been linked to the pathogenesis of multiple myeloma (MM). Redox active iron chelators have gained attention as potential anti-cancer agents as they target the high iron dependency of cancer cells. In this study, we explored the potential mechanisms underlying the anti-MM effect of redox active iron chelator Dp44mT. We tested the effect of Dp44mT on both immunomodulatory drug (IMiD)-sensitive and IMiD resistant MM cell lines using MTT assay. To explore the mechanisms of Dp44mT action in MM cells, we utilized proteomic and phosphoproteomics characterization. In addition, RT-PCR assay was performed to examine the expression pattern of major iron metabolism genes. We also measured reactive oxygen species, lipid peroxidation, mitochondrial membrane potential, and intracellular iron compartmentalization using flow-cytometry. We confirmed the high potency of Dp44mT in killing MM cell lines. Treatment with Dp44mT showed evidence of deregulated cellular iron metabolism, ROS homeostasis, and mitochondrial membrane potential in MM cell lines. As possible mechanistic pathways of Dp44mT effect on MM cells, there was overrepresentation of AMPK pathway, cell cycle, endoplasmic stress, and down regulation of ACSL4. Our studies confirm a potent anti-MM effect of Dp44mT which is likely mediated through dysregulated iron metabolism, ROS, and multiple other biological pathways.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell

DISEASE(S): Multiple Myeloma

SUBMITTER: Akhilesh Pandey  

LAB HEAD: Akhilesh Pandey

PROVIDER: PXD059741 | Pride | 2026-01-23

REPOSITORIES: Pride