INDUCTION OF DIFFERENTIATION OF THE HUMAN HISTOCYTIC LYMPHOMA CELL-LINE U-937 BY HYPERICIN

Hypericin, a photosensitizing plant pigment, was found to be a potent inducer of differentiation of human myeloid leukemia U-937 cells. At a concentration of 0.2 mu M, hypericin exhibited 50% growth inhibition. An effect on cell differentiation by hypericin was assessed by its ab ility to induce phagocytosis of latex particles, and to reduce nitrobl ue tetrazolium (NET). Approximately 51% of 0.2 mu M hypericin-treated cells were stained with NET and 63% showed phagocytic activity. In ord er to establish whether hypericin induces differentiation of U-937 cel ls to macrophage or granulocyte, esterase activities and cell sizes we re measured. When U-937 cells were treated with 0.2 mu M and 0.15 mu M Of hypericin, the alpha-naphthyl acetate esterase activity was increa sed by 38.4% and 48.1%, respectively, but naphthol AS-D chloroacetate esterase activity was not influenced. The size of hypericin-treated ce lls in terms of cell mass was larger than that observed in untreated c ells as determined by flow cytometry. Protein kinase C (PKC) inhibitor , NA-382, decreased the NET reducing activity of hypericin, whereas a cAMP-dependent protein kinase A (PKA) inhibitor, H-89, did not show an y influence on the differentiation. These results indicate that hyperi cin triggers differentiation toward monocyte:macrophage lineage by PKC stimulation.