Arsenic trioxide induces apoptosis via the mitochondrial pathway by upregulating the expression of Bax and Bim in human B cells

Int J Oncol. 2007 Feb;30(2):313-8.


Arsenic trioxide (As2O3) has been approved for the treatment of acute promyelocytic leukemia (APML) and it is a promising candidate for the treatment of patients with lymphoproliferative disorders, such as relapsed or refractory multiple myeloma and myelodysplastic syndromes. The effects of As2O3 on B cells, specifically which do not express Bcl-2, have not been studied. In this study, we have demonstrated that As2O3, at clinically achievable therapeutic concentrations, induces apoptosis in Bcl-2 negative human B cell line Ramos. As2O3-induced apoptosis is associated with reduced mitochondrial transmembrane potential (delta psi), enhanced generation of intracellular reactive oxygen species (ROS), release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria into cytoplasm, activation of caspases, and upregulation of Bax and Bim expression. Exogenous glutathione (GSH) reverses the As2O3-induced apoptosis in a dose-dependent manner. Altogether, these data indicate that As2O3 induces apoptosis in B cells, regardless of Bcl-2 expression, via the mitochondrial pathway by enhancing oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis Inducing Factor / metabolism
  • Apoptosis Regulatory Proteins / biosynthesis*
  • Apoptosis*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • B-Lymphocytes / metabolism*
  • Bcl-2-Like Protein 11
  • Cytochromes c / metabolism
  • Cytoplasm / metabolism
  • Humans
  • Leukemia, Promyelocytic, Acute / metabolism
  • Male
  • Membrane Potentials
  • Membrane Proteins / biosynthesis*
  • Mitochondria / metabolism*
  • Oxidative Stress
  • Oxides / pharmacology*
  • Proto-Oncogene Proteins / biosynthesis*
  • Up-Regulation*
  • bcl-2-Associated X Protein / biosynthesis*


  • Antineoplastic Agents
  • Apoptosis Inducing Factor
  • Apoptosis Regulatory Proteins
  • Arsenicals
  • BCL2L11 protein, human
  • Bcl-2-Like Protein 11
  • Membrane Proteins
  • Oxides
  • Proto-Oncogene Proteins
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Arsenic Trioxide