2-(3-Diethylaminopropyl)-8,8-dipropyl-2-azaspiro[4,5] decane dimaleate (Atiprimod) induced apoptosis in multiple myeloma (MM) cells

06-21-2006

According to a study from the United States, "MM accounts for 1% of all cancer deaths. Although treated aggressively, almost all myelomas eventually recur and become resistant to treatment."

"Atiprimod has exerted anti-inflammatory activities and inhibited osteoclast-induced bone resorption in animal models and been well tolerated in patients with rheumatoid arthritis in phase I clinical trials. Therefore, we investigated its activity in MM cells and its mechanism of action," explained M. Amitvazina and colleagues, M.D. Anderson Cancer Center.

"We found that Atiprimod inhibited proliferation of the myeloma cell lines U266-B1, OCI-MY5, MM-1, and MM-1R in a time- and dose-dependent manner. Atiprimod blocked U266-B1 myeloma cells in the G0 /G1 phase, preventing cell cycle progression. Furthermore, Atiprimod inhibited signal transducer and activator of transcription (STAT) 3 activation, blocking the signaling pathway of interleukin-6, which contributes to myeloma cell proliferation and survival, and downregulated the antiapoptotic proteins Bcl-2, Bcl-X-L, and Mcl-1," stated the investigators.

"Incubation of U266-B1 myeloma cells with Atiprimod induced apoptosis through the activation of caspase 3 and subsequent cleavage of the DNA repair enzyme poly(adenosine diphosphate-ribose) polymerase. Finally, Atiprimod suppressed myeloma colony-forming cell proliferation in fresh marrow cells from five patients with newly diagnosed MM in a dose-dependent fashion."

The researchers concluded, "These data suggest that Atiprimod has a role in future therapies for MM."

Amitvazina and colleagues published the results of their research in British Journal of Cancer (Atiprimod blocks STAT3 phosphorylation and induces apoptosis in multiple myeloma cells. Br J Cancer, 2005;93(1):70-80).

For additional information, contact Z. Estrov, University of Texas, MD Anderson Cancer Center, Dept. Leukemia, Unit 428, 1515 Holcombe Blvd., Houston, TX 77030, USA.

Keywords: Houston, Texas, United States, Animal Models, Antiinflammatory, Apoptosis, Arthritis, Clonogenic Assay, DNA Repair, DNA Research, Deoxyribonucleic Acid, Multiple Myeloma, Nuclear Factor Kappa B, Oncology, Proteomics, Rheumatoid Arthritis, Signal Transduction.

This article was prepared by Cancer Weekly editors from staff and other reports. Copyright 2006, Cancer Weekly via NewsRx.com.