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

Abstract: Signaling pathways such as increased ceramide, mitochondrial dysfunction, and P3 and caspase activation are produced by anticancer drugs and lead to apoptosis. In this research we show that the first event after culturing the yeast Candida utilis in the presence of low doses of doxorubicin (25 μg/mL) is the morphological alteration of the plasma membrane. In the presence of higher doxorubicin doses (≥50 μg/mL), in addition to profound alterations in the plasma membrane, changes in mitochondrial shape and cristae organization were observed. Concomitantly, increases in respiration, substrate oxidation, and cytochrome biosynthesis were observed at low doxorubicin doses (up to 25 μg/mL), whereas a progressive decrease was observed at higher doses. [3H]Leu incorporation into proteins increased by 40% in the mitochondrial fraction and by 19% in the cytosol in the presence of 25 μg/mL doxorubicin; it decreased to 80% of the control in the cytosol in the presence of 1 mg/mL doxorubicin. Morphologically, doxorubicin doses of up to 200 μg/mL produced apoptosis, whereas higher doxorubicin doses produced necrosis.