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

Physiol Res. 1999;48(2):135-41.


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 HL60 cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amiloride / analogs & derivatives*
  • Amiloride / pharmacology
  • Anthracenes
  • Antineoplastic Agents / pharmacology*
  • Drug Synergism
  • Enzyme Inhibitors / pharmacology*
  • HL-60 Cells
  • Humans
  • Leukemia / drug therapy
  • Leukemia / metabolism
  • Omeprazole / pharmacology*
  • Perylene / analogs & derivatives*
  • Perylene / pharmacology
  • Radiation-Sensitizing Agents / pharmacology*
  • Sodium-Hydrogen Exchangers / antagonists & inhibitors
  • Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors


  • Anthracenes
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Radiation-Sensitizing Agents
  • Sodium-Hydrogen Exchangers
  • 5-dimethylamiloride
  • Perylene
  • Amiloride
  • hypericin
  • Sodium-Potassium-Exchanging ATPase
  • Omeprazole