The gold compound auranofin induces apoptosis of human multiple myeloma cells through both down-regulation of STAT3 and inhibition of NF-κB activity

Constitutive activation of NF-kappa B and STAT3 plays an important role in the cellular proliferation and survival of multiple myeloma cells. We first found that auranofin (AF), a coordinated gold compound, induced a significant level of cell cycle arrest at G1 phase and subsequent apoptosis of myeloma cells. Further, AF inhibited constitutive and IL-6-induced activation of JAK2 and phosphorylation of STAT3 followed by the decreased expression of Mcl-1. AF down-regulated the activation of NF-kappa B, and the combination of AF and a specific NF-kappa B inhibitor resulted in a marked decrease of Mcl-1 expression. These results suggest that AF inhibits both IL-6 induced-JAK/STAT pathway and NF-kappa B activation in myeloma cells. (C) 2010 Elsevier Ltd. All rights reserved.