Mitochondrial-derived ROS in edelfosine-induced apoptosis in yeasts and tumor cells

Area of Science:

• Cell Biology
• Biochemistry
• Pharmacology

Background:

• 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3, edelfosine) is an alkylphosphocholine with demonstrated antitumor activity.
• The precise mechanisms underlying edelfosine's cytotoxicity, particularly its role in inducing apoptosis, require further elucidation.

Purpose of the Study:

• To investigate if the cytotoxic mechanism of edelfosine in human tumor cells is conserved in yeast.
• To explore the role of reactive oxygen species (ROS) and mitochondrial function in edelfosine-induced apoptosis.

Main Methods:

• Assessed ROS generation using a modified nitro blue tetrazolium assay.
• Detected apoptotic yeast cells via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.
• Utilized cytofluorimetric analysis for DNA fragmentation and ROS measurement in Jurkat cells.

Main Results:

• Edelfosine induced apoptosis and ROS generation in Saccharomyces cerevisiae, inhibited by rotenone and alpha-tocopherol.
• Edelfosine increased ROS in human leukemic cells prior to apoptosis; Bcl-2 overexpression abrogated these effects.
• Mitochondrial membrane potential changes were observed in both yeast and Jurkat cells.

Conclusions:

• Edelfosine induces apoptosis in yeast and human tumor cells through a mitochondrion-dependent pathway involving ROS.
• Yeast serves as a viable model for studying the antitumor mechanisms of edelfosine.