Arsenic trioxide therapy in acute promyelocytic leukemia and beyond: from bench to bedside

Abstract

Arsenic trioxide (As₂O₃) has a long history of use in medicine. However, it was almost forgotten in Western medicine in the recent centuries. Prompted by reports from China about successful treatment of acute promyelocytic leukemia (APL) with As₂O₃, there was again increasing interest in this drug in the 1990s. This review summarizes the considerable knowledge about the mechanisms of action of As₂O₃ that was gained during the last 5 - 10 years. It is focused in particular on the effects of As₂O₃ in non-APL cells. Since As₂O₃ seems to induce apoptosis and inhibits growth in a large variety of cellular targets, it might become an alternative or adjunct drug to conventional chemotherapy. As₂O₃ can even be effective in cells resistant to conventional cytostatic agents. Insight into the cellular mechanisms, in particular the impact of the redox state on sensitivity towards As₂O₃ opens the possibility to enhance As₂O₃ effects by appropriate combination therapies.

• Arsenic trioxide
• Acute promyelocytic leukemia
• Multiple myeloma
• Tumor therapy
• Caspases
• ROS
• Apoptosis