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

L. MIROSSAY, A. MIROŠŠAY, E. KOČIŠOVÁ¹, I. RADVÁKOVÁ, P. MIŠKOVSKݹ, J. MOJŽIŠ

Department of Pharmacology, Faculty of Medicine and 1Department of Biophysics, Faculty of Nature Sciences, Šafárik University, Košice, Slovak Republic

Received June 30, 1998
Accepted November 10, 1998

Summary
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 HL-60 cell line.

Key words
Hypericin · Omeprazole · Amiloride · HL-60 · Cytotoxic activity