Table of Contents
Metal-Based Drugs
Volume 2008, Article ID 260146, 13 pages
http://dx.doi.org/10.1155/2008/260146
Review Article

Arsenic-Based Antineoplastic Drugs and Their Mechanisms of Action

School of Medical Sciences, Griffith University, Parklands Drive, Southport, Queensland 4215, Australia

Received 1 April 2007; Revised 3 July 2007; Accepted 17 August 2007

Academic Editor: Rafael Moreno-Sanchez

Copyright © 2008 Stephen John Ralph. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Arsenic-based compounds have become accepted agents for cancer therapy providing high rates of remission of some cancers such as acute promyelocytic leukemia (APL). The mechanisms by which arsenic-containing compounds kill cells and reasons for selective killing of only certain types of cancer cells such as APLs have recently been delineated. This knowledge was gained in parallel with increasing understanding and awareness of the importance of intracellular redox systems and regulation of the production of reactive oxygen species (ROS) by controlling mitochondrial function. Many of the targets for the arsenic-containing compounds are mitochondrial proteins involved in regulating the production of ROS. Inhibition of these proteins by disulfide linkage of vicinal thiol groups often leads to increased production of ROS and induction of apoptotic signalling pathways. Sensitivity or resistance to the actions of arsenic-containing compounds on cancer cells and normal cells depends on the levels of transport systems for their uptake or efflux from the cells as well as their redox defence mechanisms. The exact mechanisms of arsenic toxicity as well as its anticancer properties are likely to be related and these aspects of arsenic metabolism are covered in this review. Greater understanding of the mechanisms of action of arsenic will help determine the risks of human exposure to this chemical. Novel organic arsenic-containing compounds and the lessons learned from studying their selective sensitivity in targeting dividing endothelial cells to inhibit angiogenesis raise the future possibility for designing better targeted antineoplastic arsenic-containing compounds with less toxicity to normal cells.