Potentiation of hypericin and hypocrellin-induced phototoxicity by omeprazole.
Hypericin and hypocrellin are potential antiviral and antineoplastic agents with multiple modes of light-induced biological activity connected with a production of singlet oxygen and/or excited-state proton transfer and consequent pH drop formation in the drugs environment. In present work light-induced cytotoxicity of hypericin (1 x 10(-5) - 10(-9) mol) and hypocrellin (1 x 10(-5) - 10(-9) mol) and potentiating effect of omeprazole on human leukemic cell line HL-60 was studied. Under dark condition cultivation none cytotoxicity was observed. The only one exception was hypocrellin in concentration 1 x 10(-5) mol which displayed full cytotoxic effect. However, illumination increased cytotoxic effect of hypericin and hypocrellin, both. Omeprazole, an inhibitor of H+K+-ATPase, has been used for testing the hypothetical pH decreasing effect of hypericin and hypocrellin in their cytotoxic mechanism of action. The results of our experiments have shown that in HL-60 cell line the effect of hypericin and hypocrellin at 1 x 10(-6) mol (both) was significantly potentiated by omeprazole in concentrations 1 x 10(-6) - 10(-9) mol. Our results support the hypothesis that the excited-state proton transfer and the consequent acidification of hypericin and hypocrellin environment could play a role in the biological activity of both agents.
Mirossay
A
A
Department of Pharmacology, Medical Faculty, P. J. Safarik University, Kosice, Slovak Republic.
Mirossay
L
L
Tóthová
J
J
Miskovský
P
P
Onderková
H
H
Mojzis
J
J
D000873:Anthracenes; D000970:Antineoplastic Agents / Q000819:agonists / Q000494:pharmacology; D000998:Antiviral Agents / Q000819:agonists / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D018922:HL-60 Cells; D006801:Humans; D009853:Omeprazole / Q000494:pharmacology*; D010569:Perylene / Q000819:agonists / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019800:Phenol; D017319:Photosensitizing Agents / Q000819:agonists / Q000494:pharmacology*; D011809:Quinones / Q000819:agonists / Q000494:pharmacology*
D000873:Anthracenes; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D017319:Photosensitizing Agents; D011809:Quinones; D019800:Phenol; D010569:Perylene; C004965:hypericin; D009853:Omeprazole; C048388:hypocrellin A