POTENT GROWTH-INHIBITORY ACTIVITY OF A NOVEL ORNITHOGALUM CHOLESTANE GLYCOSIDE ON HUMAN-CELLS - INDUCTION OF APOPTOSIS IN PROMYELOCYTIC LEUKEMIA HL-60 CELLS
T. Hirano et al., POTENT GROWTH-INHIBITORY ACTIVITY OF A NOVEL ORNITHOGALUM CHOLESTANE GLYCOSIDE ON HUMAN-CELLS - INDUCTION OF APOPTOSIS IN PROMYELOCYTIC LEUKEMIA HL-60 CELLS, Life sciences, 58(9), 1996, pp. 789-798
Citations number
22
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
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.