Protective effect of cholesterol on Friend leukemic cells against photosensitization by hematoporphyrin derivative.
The cytotoxic effects of hematoporphyrin derivative (HPD) on Friend erythroleukemic cells were studied. Upon binding of the porphyrin to the cells, the fluorescence spectra was shifted from 613 to 633 nm regarding the main band and from 676 to 667 nm concerning the secondary band. The kinetics of HPD binding was then determined. Maximum binding already occurred at 60 s after exposure of the cells to HPD. It could be demonstrated that the effect of the photoactivated HPD on cell viability was drug, dose, and light fluorescence dependent. Cellular protein synthesis and Friend virus complex release from the cells were equally inhibited by the photodynamic sensitization of the drug, indicating no specific effect on virus maturation. Since cholesterol affects the fluidity of cell membranes, it was important to study the effect of cholesterol enrichment on the photodynamic sensitization by HPD. It was found that, while a 50% reduction in protein synthesis was monitored following treatment with 20 micrograms of HPD per ml and illumination by a 6-milliwatt white light for 60 s, no inhibition was observed following preenrichment of the cells with 0.5, 1, or 2% of cholesterol hemisuccinate. The same trend of cholesterol protection was demonstrated with longer illumination periods up to 10 min. The protective effect of cholesterol hemisuccinate was also seen using scanning electron microscopy. It is thus concluded that the cholesterol hemisuccinate content of Friend erythroleukemic cell membranes is an important factor in regulating the cytotoxicity of photoactivated HPD.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D002788:Cholesterol Esters / Q000494:pharmacology; D005622:Friend murine leukemia virus / Q000187:drug effects; D006415:Hematoporphyrins / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000473:pathology*; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000473:pathology*; D010778:Photochemotherapy
D002788:Cholesterol Esters; D006415:Hematoporphyrins; D002784:Cholesterol; C013440:cholesteryl succinate