Photodynamically induced cytotoxicity of hypericin dye on human fibroblast cell line MRC5.
The possible application of hypericin (hyp) in the photodynamic therapy (PDT) of cancer was investigated using the human fibroblast cell line MRC5. In aerobic conditions, at pH 7.4, irradiation of MRC5 cells was carried out with different doses of visible light and different doses of hyp. A low concentration of hyp (5 x 10(-9) M) was highly toxic to MRC5 cells, producing 15% survival for an irradiation period of 40 min. In the dark, no cytotoxicity was observed in the range 10(-9)-10(-7) M hyp. The mechanism of cell killing by hyp was also examined. Significant inhibition of MRC5 killing was observed on addition of 1,4-diazabicyclo[2,2,2]octane (DABCO) or histidine, known quenchers of type II mechanisms. In addition, the photodynamic effect of hyp was enhanced by deuterium oxide. The addition of desferrioxamine, catalase or superoxide dismutase (SOD), known scavenging agents of the type I mechanism, had a significant inhibitory effect on the rate of photodynamic action of hyp. The experimental results suggest that hyp has considerable potential for use as a sensitizer in the PDT of cancer.
Hadjur
C
C
Laboratoire de Photochimie, Université Joseph Fourier, Grenoble, France.
Richard
M J
MJ
Parat
M O
MO
Favier
A
A
Jardon
P
P
D000873:Anthracenes; D002374:Catalase / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D003624:Darkness; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006639:Histidine / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008027:Light; D010569:Perylene / Q000031:analogs & derivatives* / Q000633:toxicity; D010778:Photochemotherapy; D010879:Piperazines / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors
D000873:Anthracenes; D010879:Piperazines; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D006639:Histidine; D010569:Perylene; C004965:hypericin; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; C007306:triethylenediamine