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 microM, hypericin exhibited 50% growth inhibition. An effect on cell differentiation by hypericin was assessed by its ability to induce phagocytosis of latex particles, and to reduce nitroblue tetrazolium (NBT). Approximately 51% of 0.2 microM hypericin-treated cells were stained with NBT and 63% showed phagocytic activity. In order to establish whether hypericin induces differentiation of U-937 cells to macrophage or granulocyte, esterase activities and cell sizes were measured. When U-937 cells were treated with 0.2 microM and 0.15 microM of hypericin, the alpha-naphthyl acetate esterase activity was increased by 38.4% and 48.1%, respectively, but naphthol AS-D chloroacetate esterase activity was not influenced. The size of hypericin-treated cells in terms of cell mass was larger than that observed in untreated cells as determined by flow cytometry. Protein kinase C (PKC) inhibitor, NA-382, decreased the NBT reducing activity of hypericin, whereas a cAMP-dependent protein kinase A (PKA) inhibitor, H-89, did not show any influence on the differentiation. These results indicate that hypericin triggers differentiation toward monocyte/macrophage lineage by PKC stimulation.
Kim
J I
JI
Kyung Hee University, Seoul, Korea.
Park
J H
JH
Park
H J
HJ
Choi
S K
SK
Lee
K T
KT
D000873:Anthracenes; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004950:Esterases / Q000378:metabolism; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D009580:Nitroblue Tetrazolium; D010084:Oxidation-Reduction; D010569:Perylene / Q000031:analogs & derivatives* / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000873:Anthracenes; D009580:Nitroblue Tetrazolium; D010569:Perylene; C004965:hypericin; D004950:Esterases