title: Hypericin-induced phototoxicity of human leukemic cell line HL-60 is potentiated by omeprazole, an inhibitor of H+K+-ATPase and 5'-(N,N-dimethyl)-amiloride, an inhibitor of Na+/H+ exchanger.
abstract: Hypericin, an antiretroviral and antineoplastic agent, seems to have multiple modes of light-induced biological activity connected with the production of single oxygen and/or excited-state proton transfer and a consequent pH drop of pH formation in the hypericin environment. In the present study omeprazole, an inhibitor of H+K+-ATPase, and amiloride, an inhibitor of the Na+/H+ exchanger, have been used for testing the hypothetical pH decreasing effect of hypericin in its antineoplastic action. The results of our experiments have shown that in the HL-60 cell line the effect of hypericin (10(-6) mol.l(-1)) was significantly potentiated by omeprazole and 5'-(N,N-dimethyl)-amiloride. The effect of omeprazole seemed to be less specific than that of 5'-(N,N-dimethyl)-amiloride. Our results support the hypothesis that the excited-state proton transfer and the consequent acidification of the hypericin environment could play a role in the biological activity of hypericin. Moreover, both omeprazole and 5'-(N,N-dimethyl)-amiloride are effective potentiating agents of hypericin cytotoxic effect in the HL60 cell line.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Safárik University, Kosice, Slovak Republic. mirossay@central.medic.upjs.sk
authors.forename: L
authors.initials: L
authors.lastname: Mirossay
authors.forename: A
authors.initials: A
authors.lastname: Mirossay
authors.forename: E
authors.initials: E
authors.lastname: Kocisová
authors.forename: I
authors.initials: I
authors.lastname: Radváková
authors.forename: P
authors.initials: P
authors.lastname: Miskovský
authors.forename: J
authors.initials: J
authors.lastname: Mojzis
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology; D000873:Anthracenes; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D009853:Omeprazole / Q000494:pharmacology*; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011838:Radiation-Sensitizing Agents; D017923:Sodium-Hydrogen Exchangers; C039465:5-dimethylamiloride; D010569:Perylene; D000584:Amiloride; C004965:hypericin; D000254:Sodium-Potassium-Exchanging ATPase; D009853:Omeprazole