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Potentiation of hypericin and hypocrellin-induced phototoxicity by omeprazole.
Authors:A Mirossay  L Mirossay  J Tóthová  P Miskovsky  H Onderková  J Mojzis
Institution:Department of Pharmacology, Medical Faculty, P. J. Safarik University, Kosice, Slovak Republic.
Abstract: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.
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