Plasma Membrane Alteration Is an Early Signaling Event in Doxorubicin-Induced Apoptosis in the Yeast Candida utilis

doi:10.1196/annals.1329.046

Signaling pathways such as increased ceramide, mitochondrialdysfunction, and P3 and caspase activation are produced by anticancerdrugs and lead to apoptosis. In this research we show that thefirst event after culturing the yeast Candida utilis in thepresence of low doses of doxorubicin (25 µg/mL) is themorphological alteration of the plasma membrane. In the presenceof higher doxorubicin doses ( $≥$ 50 µg/mL), in addition toprofound alterations in the plasma membrane, changes in mitochondrialshape and cristae organization were observed. Concomitantly,increases in respiration, substrate oxidation, and cytochromebiosynthesis were observed at low doxorubicin doses (up to 25µg/mL), whereas a progressive decrease was observed athigher doses. [³H]Leu incorporation into proteins increasedby 40% in the mitochondrial fraction and by 19% in the cytosolin the presence of 25 µg/mL doxorubicin; it decreasedto 80% of the control in the cytosol in the presence of 1 mg/mLdoxorubicin. Morphologically, doxorubicin doses of up to 200µg/mL produced apoptosis, whereas higher doxorubicin dosesproduced necrosis.