THE ROLE OF LIPID PEROXIDATION AND PROTEIN DEGRADATION IN THE PHOTODESTRUCTION OF EHRLICH ASCITES CARCINOMA CELLS SENSITIZED BY HEMATOPORPHYRIN DERIVATIVE
In the work, a comparative study on the role of peroxidation of lipids and degradation of proteins in inactivation of tumor cells by photodynamic therapy (PDT) with hematoporphyrin derivative (HPD) was performed. Ehrlich ascites carcinoma (EAC) cells were pre-incubated with HPD in a serum-free medium and then irradiated with red light at 630 nm. The rate of lipid peroxidation was estimated by measuring of accumulations of conjugated dienes (CD) and malondialdehyde (MDA). It was found that irradiation of EAC cells led to a powerful inhibition of their glycolytic and respiratory activity, and notably lowered the content of adenosine triphosphate. Studies pointed to the very low probability that the HPD-PDT induced impairment of mitochondria and, as a consequence, cell death were mediated by the peroxidation of membrane lipids. At a light dose causing a strong (> 2-fold) decrease in the respiratory activity of EAC cells as well as inactivation of ~ 98% of the cells, as estimated by MTT-test, only very small amounts of CD and MDA were detected. However, we found that cell proteins were substantially more sensitive to the damaging influence of HPD-PDT than lipid components; a clearly expressed fall in the content of protein-bound SH groups and, especially, histidine was registered. Our data suggest that cell proteins, but not lipids, are the primary target of PDT with HPD in EAC cells.
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