Arsenic: A double-edged sword

Arsenic may be a killer or a life-saver, and researchers are suggesting that the same cellular mechanisms may be responsible for both effects.

Arsenic compounds are well known to be highly poisonous to all forms of life, and chronic exposure to them is associated with many different diseases, including various types of cancer. Arsenic is also widely used in agriculture and industry, and approximately 100 million people worldwide are still exposed to arsenic-contaminated groundwater.

But arsenic compounds such as arsenic trioxide (As₂O₃) have also been used medicinally for thousands of years. For example, their ability to induce apoptosis, or programmed cell death, makes them useful anti-cancer drugs.

Researchers from Germany and Qatar have reviewed the effects of different arsenic compounds used today on living organisms, publishing their work in the Journal of Local and Global Health Science¹.

Acute arsenic poisoning causes vomiting, nausea, diarrhoea, and kidney failure, among other symptoms. Long-term exposure significantly increases the risk of heart disease, diabetes, and makes numerous different cell types turn cancerous. Arsenic also targets the nervous system, causing a wide variety of neurological and cognitive impairments.

The cellular effects of arsenic compounds are, however, poorly understood. Various mechanisms for their carcinogenic effects have been suggested, including chromosomal damage, alterations in gene expression and regulation, disruption of DNA repair mechanisms, and interference with immune system function.

Calcium signalling plays a vital role in all cellular processes, and sudden increases in the concentration of calcium ions inside cells can trigger apoptosis. Research shows that As₂O₃ increases intracellular calcium ion concentration irreversibly. Furthermore, cultured cells treated with the compound exhibit all the hallmarks of apoptosis, such as DNA fragmentation and increased expression of so-called ‘cell death’ proteins such as caspase-3.

“While As₂O₃ is toxic for many different cells in the body, leukaemia cells have a higher sensitivity,” says Dietrich Büsselberg from Weill Cornell Medical College in Qatar. “In a very specific concentration range, apoptosis is induced in these cells, while most of the other cells still survive.”

Many different human diseases involve altered cell mechanisms. In cancer, for example, cells that would normally have a finite lifetime become immortal, such that their uncontrolled division leads to tumour growth. A better understanding of how arsenic compounds exert their cellular effects could, therefore, eventually lead to improved cancer treatments.   

“There is an enormous need to understand the mechanisms by which anti-cancer drugs induce cell death,”adds Büsselberg, in order to achieve synergy between different therapeutic agents.

1. Florea, A.-M. &Büsselberg, D. The two opposite facets of arsenic: toxic and anticancer drug. J. Local Global Health Sci. 2013, 1 (2013). | article