Modulation of the phototoxic effect of hypericin in human leukemia CEM cell line by N-ethylmaleimide, amiloride and omeprazole.

Mirossay A, Mirossay L, Sarissky M, Papp P, Mojzis J.

Department of Pharmacology, Medical Faculty, P.J. Safarik University, Tr. SNP 1, 040 66 Kosice, Slovak Republic.mojzis@central.medic.upjs.sk

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.

PMID: 12511190