The metal-coordinated Casiopeína IIIEa induces the petite-like phenotype in Saccharomyces cerevisiae

Abstract

The Casiopeínas® are mixed chelate copper (II) complexes and promising antineoplastics agents against cancer cells and tumors in vitro and in vivo. However, the action mode of these compounds is poorly characterized. In this work the effect of the antineoplastic Casiopeína IIIEa on the metabolism and ultrastructure of the yeast Saccharomyces cerevisiae was investigated. Exposure of cells growing in rich or in low-iron medium to 5 μM of the compound decreased duplication time and reduced oxygen consumption. Those cells formed smaller colonies when growing in a non-fermentable carbon source and low-iron medium, and under the light microscope, multiple folds were observed along the plasma membrane accompanied with a reduction in the diameter of the yeast. These observations were confirmed under the electron microscope, which also revealed a slight reduction of the mitochondrial size. A correlation was found with smaller colonies exhibiting lower rates of oxygen consumption, and yeast labelled with fluorescent MitoTracker(TM) consistently exhibited reduced mitochondrial activity. It appears that Casiopeína IIIEa gives rise to smaller yeast and petite-like colonies by reducing the mitochondrial respiratory activity without significantly affecting the mitochondrial structure.

Cytotoxic phenanthroline derivatives alter metallostasis and redox homeostasis in neuroblastoma cells

“…These compounds have been found to cause tumour cell death by apoptosis [ 35 , 36 ], both in caspase dependent and independent mechanisms [ 27 , 31 , 36 ], as well as by autophagy [ 32 ]. The activities of these metal complexes seem to be linked to: i) generation of ROS [ 31 , 37 ] with DNA oxidation and degradation [ 38 , 39 ], with concomitant depletion of antioxidants such as glutathione (GSH) [ 40 , 41 ]; ii) mitochondrial toxicity [ 28 , 30 , 42 ] and iii) DNA damage through direct interaction with metal complexes (the interaction may take place through intercalation, coordination of the metal to the negatively charged phosphate groups, insertion into the minor groove, partial substitution of some coordinating groups in DNA) [ 43 – 45 ].…”