Relationship between Cell Cycle Changes and Variations of the Mitochondrial Membrane Potential Induced by Etoposide

摘要

Etoposide, a clinically useful anticancer drug, is a potent inhibitor of topoisomerase II. The DNA strand I>reaks caused by this epipodophyllotoxin lead to iipoptotic death of tumor cells. Flow cytometry was llsed to investigate the relationship between the ef- [ects of the drug on the cell cycle of human leukemia EIL-60 cells and the variations of the mitochondrial ~ransmembrane potential (/1. 'l1 mJ. Three cationic fluo- rescent probes, DiOC6, JC-l, and TMRM, were used to neasure drug-induced changes of /1. 'l1 mt. In all three ~ases, we found that the arrest in the G2/M phase of ;he cells treated with 0.5 ILM etoposide is associated with an increase in the potential of mitochondrial nembranes whereas treatment with a tenfold higher lrug concentration trigger massive apoptosis and a ~ollapse of /1.'l1mt. DNA fragmentation (TUNEL assay) md externalization of phosphatidylserine residues in ,he outer leaflet of the plasma membrane (annexin V }inding) were measured to characterize the apoptotic :ell population.