Osalmid

Multiple 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.

We 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.

The 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.

The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, characterized by high heterogeneity. The poor outcome of a portion of patients who suffer relapsing or resistant to conventional treatment impels the development of novel agents for DLBCL. DCZ0825 is a novel compound derived from pterostilbene and osalmide, whose antitumor activities have drawn our attention. In this study, we found that DCZ0825 exhibited high cytotoxicity toward DLBCL cell lines in a dose- and time-dependent manner, as revealed by cell counting kit-8 assay. Flow cytometry and western blot analysis results showed that DCZ0825 also promoted cell apoptosis via both extrinsic and intrinsic apoptosis pathways mediated by caspase. In addition, DCZ0825 induced cell cycle arrest in the G2/M phase by downregulating Cdc25C, CDK1, and Cyclin B1, thus interfering with cell proliferation. Further investigation showed the involvement of the phosphatidylinositol 3-kinase (PI3K)‒AKT‒mTOR/JNK pathway in the efficacy of DCZ0825 against DLBCL. Remarkably, DCZ0825 also exerted notable cytotoxic effects in vivo as well, with low toxicity to important internal organs such as the liver and kidney. Our results suggest that DCZ0825 may have the potential to become a novel anti-DLBCL agent or to replenish the conventional therapeutic scheme of DLBCL.