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

Hypericin, an antiretroviral and antineoplastic agent, seems to have multip le 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 ome prazole, an inhibitor of H+K+-ATPase, and amiloride, an inhibitor of the Na +/H+ exchanger, have been used for testing the hypothetical pH decreasing e ffect of hypericin in its antineoplastic action. The results of our experim ents 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-dimethy l)-amiloride. The effect of omeprazole seemed to be less specific than that of 5'-(N,N-dimethyl)-amiloride. Our results support the hypothesis that th e excited-state proton transfer and the consequent acidification of the hyp ericin environment could play a role in the biological activity of hyperici n. Moreover, both omeprazole and 5'-(N,N-dimethyl)-amiloride are effective potentiating agents of hypericin cytotoxic effect in the HL-60 cell line.