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 glyco side found in bulbs of Ornithogalum saundersiae were examined in vitro using human promyelocytic leukemia HL-60 cells, human T-lymphocytic l eukemia MOLT-4 cells, and mitogen-stimulated human peripheral-blood mo nonuclear cells (PBMC). The growth of HL-60 cells and MOLT-4 cells was strongly suppressed in the presence of the glycoside; the IC(50)s of which were 21.0 and 18.0 nM, respectively. Suppressive effect of the g lycoside 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 glyco side-treated HL-60 cells also demonstrated apoptotic cells with low DN A content and showed a decrease of G0/G1 cells and a concomitant incre ase of S and/or G2/M cells. The growth inhibiting effect of the glycos ide on HL-60 cells was promoted by calcium and was inhibited in the pr esence of zinc, which support involvement of endonuclease activation i n the glycoside-induced apoptosis. The glycoside also inhibited mitoge n-stimulated blastogenesis of PBMC, the IC50 of which was 6.2 nM. Thes e results provided the first evidence ever for the potent growth inhib itory activity of Ornithogalum glycoside on human leukemia cell lines and PBMC.