Potent growth inhibitory activity of a novel Ornithogalum cholestane glycoside on human cells: induction of apoptosis in promyelocytic leukemia HL-60 cells.
Growth inhibitory activities of a novel 22-homo-23-norcholestane glycoside found in bulbs of Ornithogalum saundersiae were examined in vitro using human promyelocytic leukemia HL-60 cells, human T-lymphocytic leukemia MOLT-4 cells, and mitogen-stimulated human peripheral-blood mononuclear cells (PBMC). The growth of HL-60 cells and MOLT-4 cells was strongly suppressed in the presence of the glycoside; the IC50s of which were 21.0 and 18.0 nM, respectively. Suppressive effect of the glycoside on HL-60 cell growth appears to be mediated partially through induction of apoptosis which was demonstrated by the presence of DNA fragmentation of the leukemic cells. Flow cytometric analysis of glycoside-treated HL-60 cells also demonstrated apoptotic cells with low DNA content and showed a decrease of G0/G1 cells and a concomitant increase of S and/or G2M cells. The growth inhibiting effect of the glycoside on HL-60 cells was promoted by calcium and was inhibited in the presence of zinc, which support involvement of endonuclease activation in the glycoside-induced apoptosis. The glycoside also inhibited mitogen-stimulated blastogenesis of PBMC, the IC50 of which was 6.2 nM. These results provided the first evidence ever for the potent growth inhibitory activity of Ornithogalum glycoside on human leukemia cell lines and PBMC.
Hirano
T
T
Department of Clinical Pharmacology, Tokyo College of Pharmacy, Japan.
Oka
K
K
Mimaki
Y
Y
Kuroda
M
M
Sashida
Y
Y
D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002770:Cholenes / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D018517:Plant Roots; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002770:Cholenes; D006027:Glycosides; D007166:Immunosuppressive Agents; C098417:3-((2-O-(6-deoxy-4-O-(4-hydroxybenzoyl)mannopyranosyl)glucopyranosyl)oxy)-16,23-epoxy-23-hydroxy-22-(2-methyl-1-propenyl)-24-norchol-5-en-18-al