Abstract
BackgroundMultiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity.MethodsWe used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro.ResultsThe results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed.ConclusionThe findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.
Highlights
Multiple myeloma (MM) is the second most common malignancy in the hematologic system and is characterized by the latent accumulation of secretory plasma cells in bone marrow [1]
The results showed that DCZ0805 exerts its cytotoxic effects in a dose-dependent manner in MM cell lines, and in a time-dependent manner (Fig. 1c)
Involvement of the NF‐κB pathway in DCZ0805‐mediated regulation in MM cell lines Just as Nuclear factor-kappa B (NF-κB) is highly involved in the occurrence and progression of MM [15], we found that DCZ0805 treatment (0, 10 and 20 μM, for 48 h) patently suppressed the phosphorylation of IκBα and NF-κB-p65, with no obvious impact on total IκBα and NF-κB-p65 protein levels (Fig. 4a)
Summary
Multiple myeloma (MM) is the second most common malignancy in the hematologic system and is characterized by the latent accumulation of secretory plasma cells in bone marrow [1] To develop novel antimyeloma drugs with high efficiency and safety profiles is of great value for improving the remission rate and prolonging the overall survival of patients with MM. Natural compounds and their derivatives, such as arsenic trioxide, resveratrol, and homoharringtonine etc., have been demonstrated significant efficacy in multiple tumors, including hematological malignancies. We intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity
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