Arsenic trioxide induces apoptosis of Burkitt lymphoma cell lines through multiple apoptotic pathways and triggers antiangiogenesis

Oncol Res. 2011;19(3-4):149-63. doi: 10.3727/096504011x12935427587885.

Abstract

Burkitt lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) and it appears to be one of the most common childhood cancers in equatorial areas. Unprecedented gains have been made in the cure rates for BL during the past two decades and these reflect steady improvements in treatment protocols and a multidisciplinary approach to patient care. However, the life-threatening side effects associated with conventional treatment urge us to explore new strategies. Arsenic trioxide (ATO), a natural product that has improved the prognosis of acute promyelocytic leukemia (APL) from highly fatal to highly curable, has also been proven to be effective in treating BL cell lines through multiple pathways in our study. Our data indicates that ATO can inhibit the proliferation of BL cell lines through 1) arresting the cell cycle; 2) decreasing the respiratory function and transmembrane potential of mitochondrial; and 3) downregulating the expressions of Survivin, Bcl-2, MCL-1, and VEGF. We therefore suggest that dissecting the pharmaceutical mechanism of ATO at the molecular and cellular levels may be a good strategy to explore the value of traditional natural products in treating high malignant Burkitt lymphoma.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Arsenic Trioxide
  • Arsenicals / pharmacology*
  • Blotting, Western
  • Burkitt Lymphoma / metabolism
  • Burkitt Lymphoma / pathology*
  • Cell Proliferation
  • Flow Cytometry
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Neovascularization, Pathologic / prevention & control*
  • Oxides / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survivin
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Antineoplastic Agents
  • Arsenicals
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Myeloid Cell Leukemia Sequence 1 Protein
  • Oxides
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Survivin
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Arsenic Trioxide