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-kappa B (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 gamma-H(2)A(X) 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.