Resistance to arsenic- and antimony-based drugs.
Organic arsenicals were the first antimicrobial agents specifically synthesized for the treatment of infectious diseases such as syphilis and sleeping sickness. For the treatment of diseases caused by trypanosomatid parasites, organic derivatives of arsenic and the related metalloid antimony are still the drugs of choice. Arsenic trioxide, As203, has been used for a long time in traditional Chinese medicines for treatment of various diseases, and it has recently been shown to be clinically active in acute promyelocytic leukemias. Resistance to metalloid salts is found in bacteria, fungi, parasites and animals. In some organisms, resistance involves overproduction of intracellular thiols. In many cases, resistance to arsenic salts is the result of removal of the metalloid from the cytosol usually by extrusion from the cell. In eukaryotes resistance to arsenic and antimony is conferred by membrane transport proteins of the MRP family. The human MRP1, a member of this family, is frequently amplified in cancer cells and it is well-documented that MRPl-overexpressing cells poorly accumulate arsenic and antimony because of enhanced cellular effiux which depends on the presence of GSH.
Salerno
Milena
M
Laboratoire de Physicochimie Biomoléculaire et Cellulaire (LPBC/CSSB UMR 7033), Université Paris Nord, 74 rue Marcel Cachin, Bobigny 93017, France.
Garnier-Suillerot
Arlette
A