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SHORT
COMMUNICATION
Modulation of the Phototoxic Effect of
Hypericin in Human Leukemia CEM Cell Line by N-Ethylmaleimide,
Amiloride and Omeprazole
A. MIROŠŠAY, L. MIROSSAY, M. ŠARIŠSKÝ, P.
PAPP, J. MOJŽIŠ
Department of Pharmacology, Faculty of Medicine, P.J. Šafárik
University, Košice, Slovak Republic
Received December 17,
2001
Accepted March 25, 2002
Summary
Hypericin is a photosensitizing plant pigment from Hypericum
perforatum with multiple modes of light-induced biological
activities due to production of singlet oxygen and/or
excited-state proton transfer with consequent pH drop in the
hypericin environment. In the present work, we studied the
effects of three inhibitors of crucial mechanisms responsible
for intracellular pH (pHi) regulation on hypericin
phototoxicity: N-ethylmaleimide (NEM), an inhibitor of
H+-ATPase, 5'-(N,N-dimethyl)-amiloride (DMA), an inhibitor of
Na+/H+ exchanger, and omeprazole (OME), an inhibitor of
H+K+-ATPase. Our experiments show that the effect of hypericin
at 1x10-5 and 1x10-6 mol.l-1 was significantly potentiated by
NEM (1x10-7-1x10-9 mol.l-1) and DMA (1x10-6 and 1x10-7 mol.l-1)
in leukemic CEM cell line. On the other hand, OME had no
significant effect on hypericin cytotoxicity. Our results
support the hypothesis that the excited-state proton transfer
and the consequent acidification of hypericin environment could
play a role in the biological activity of hypericin.
Key
words
Hypericin · Phototoxicity · N-ethylmaleimide · Amiloride ·
Omeprazole · CEM cells
Reprint
requests
Assoc. Prof. DVM. Ján Mojžiš, Ph.D., Department of Pharmacology,
Medical Faculty, P.J. Šafarik University, Tr. SNP 1, 040 66
Košice, Slovak Republic. Fax: ++421 9542 8524. E-mail:
mojzis@central.medic.upjs.sk
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