Bioactive Sialoglycosphingolipids(Gangliosides) and Their Related Amphipathic Sialoglycocompounds:Fundamental Studies and Applications of Anti-Leukemic(Differentiation-Inducing) Activities

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We have recently demonstrated that the particular ganglioside molecules play an important role in regulation of differentiation of human myelogenous leukemia cell line HL-60 cells. The ganglio-series ganglioside GM3, which increases characteristically during monocytic differentiation of HL-60 cells induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA), can induce monocytic differentiation of HL-60 cells, whereas neolacto-series gangliosides, which increase characteristically during granulocytic differentiation of HL-60cells induced by retinoic acid (RA) or dimethylsulfoxide (DMSO), can induce granulocytic differentiation of HL-60 cells. These findings raise the possibility that, in addition to gangliosides, certain types of amphipathic compounds containing sialic acid might be capable of inducing the differentiation of HL-60 cells when added to the culture medium. In this context, we investigated the differentiation-inducing activity of sialocholesterols, which are synthetic amphipath … More ic glycocompounds containing sialic acid. We found that alpha-sialo-cholesterol was a potent inducer for granulocytic differentiation of HL-60 cells, and that the differentiation-inducing activity was stereospecific; that is, alpha-sialocholesterol was much more potent than beta-anomer.The differentiation of cells was dependent on the concentration of alpha-sialocholesterol and accompanied with inhibition of cell growth. Another amphipathic sialocompound, alpha-sialoglyceride, was also demonstrated to be considerably potent for inducing human myelogenous leukemia cells. Further studies with various types of synthetic sialocompounds will be needed to elucidate the structure-activity relationships in the differentiation-induction as well as the determination of differentiation-direction in HL-60 cells however, it will be certain that these sialocompounds, alpha-sialocholesterol and alpha-sialoglyceride, are best candidates ever known for anti-leukemic differentiation-inducing drugs amooth natural and synthetic sialocompounds since they were found to be much less toxic than anticipated. Less