Gefitinib induces mitochondrial-dependent apoptosis in Saccharomyces cerevisiae

Gefitinib, a selective inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, has been clinically demonstrated to be effective in certain cancer cell types. In the present study, using the yeast Saccharomyces cerevisiae as a model, gefitinib-induced apoptotic cell death was demonstrated. Gefitinib inhibited yeast cell proliferation and ultimately led to cell death in a time- and dose-dependent manner. Furthermore, when cells were exposed to 15 mu M gefitinib, typical apoptotic markers, including phosphatidylserine exposure, DNA fragmentation, reactive oxygen species production and decrease in mitochondrial membrane potential, were observed. The Delta cyc3 strain deleted in cyt c heme lyase and the rho(0) mutant strain lacking mtDNA-delayed cell death, provided further evidence that the yeast cell death process involved the mitochondria. Thus, these findings suggest that gefitinib induces apoptosis in yeast cells through a mitochondrial-dependent pathway.