Arsenic trioxide induces apoptosis in B-cell chronic lymphocytic leukemic cells through down-regulation of survivin via the p53-dependent signaling pathway

Leuk Res. 2013 Dec;37(12):1719-25. doi: 10.1016/j.leukres.2013.09.019. Epub 2013 Sep 29.

Abstract

Arsenic trioxide (As2O3) can induce apoptosis in many tumors. However, the associated mechanisms are not clearly understood. We found that As2O3 significantly inhibited the proliferation of WSU-CLL cells and induced apoptosis in dose- and time-dependent manners. WSU-CLL cells treated with 2μM As2O3 showed survivin down-regulation and p53 up-regulation. Survivin siRNA combined with As2O3 further inhibited the proliferation of WSU-CLL cells. p53 inhibition by siRNA prevented the down-regulation of survivin by As2O3 and prevented the As2O3-induced cytotoxicity of WSU-CLL cells. These results suggest that As2O3 may be of therapeutic value for chronic lymphocytic leukemia.

Keywords: Apoptosis; Arsenic trioxide; P53 and CLL; Survivin; WSU-CLL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Leukemic / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Oxides / pharmacology*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Survivin
  • Tumor Suppressor Protein p53 / physiology*
  • Up-Regulation / drug effects

Substances

  • Antineoplastic Agents
  • Arsenicals
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Oxides
  • Survivin
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Arsenic Trioxide