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. MIŠKOVSKÝ1,
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
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