Antitumoral effect of arsenic compound, sodium metaarsenite (KML001), on multiple myeloma cells

Abstract

KML001 (sodium metaarsenite;NaAs2O3) is known to have antitumor activity against a variety of cancers. In this study, we examined its effect on multiple myeloma (MM). KML001 reduced the growth of all MM cell lines examined with an IC50 of 5x10-8 M. Exposure to KML001 (5x10-8 M) decreased levels of cyclins A/B1/D1/E1, CDK2/4/6 in U266 cells and increased the p21 and p27 levels. Furthermore, p21 became bound to CDK2/4/6, resulting in a reduction of CDK2/4/6 kinase activity. The cleaved forms of Bcl-2, and caspases-3,-8 and-9 were detected, and the anti-Apoptotic molecule, Bax, also increased. Activation of STAT1/3, NF-κB (p65 and p50 subunits), pAKT and pERK decreased, and p-PTEN increased. There was also a significant reduction of hTERT at 12 h and upregulation of γ-H2AX and CHK1/2 molecules at 24 h. Thus, KML001 appears to have antitumor activity against MM by inhibiting various oncogenic signaling pathways. It may be useful for treating MM.