On the mechanism underlying calcein-induced cytotoxicity.

The cellular pharmacology of calcein acetoxymethyl ester (calcein/AM)-induced cytotoxicity was investigated in human tumor cell lines in order to identify tentative mechanisms of action. The activity profile in 10 cell lines with known mechanisms of resistance was compared with the activity profiles of standard drugs and experimental substances. The activity of calcein correlated with that of different topo II inhibitor/intercalating compounds and mitochondrial accumulating compounds, such as Rhodamine 123, Mito Fluor Green and Acridine Orange-10. Using U-937 GTB as a model cell line, calcein was found to distribute throughout the whole cell, nuclei and mitochondria included. In addition, studies of mitochondrial dehydrogenase activity and extracellular acidification rate showed an almost complete lack of dehydrogenase activity and extracellular acidification at 12 and 24 h, respectively. The results indicate that calcein/AM may induce cytotoxicity through interference with both mitochondrial and nuclear DNA.