1988 Fiscal Year Final Research Report Summary
Bioactive Sialoglycosphingolipids(Gangliosides) and Their Related Amphipathic Sialoglycocompounds:Fundamental Studies and Applications of Anti-Leukemic(Differentiation-Inducing) Activities
| Project/Area Number |
61870050
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
SAITO Masaki Jichi Medical School, Professor, 医学部, 教授 (60012762)
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| Co-Investigator(Kenkyū-buntansha) |
ITOH Masayoshi MECT Manager, 課長
NOJIRI Hisao Jichi Medical School, Associate, 医学部, 助手 (70180742)
NAKAMURA Mitsuru Jichi Medical School, Associate, 医学部, 助手 (20198237)
OHTA Masatsugu Jichi Medical School, Lecturer, 医学部, 講師 (90160514)
KITAGAWA Sei-ichi Jichi Medical School, Lecturer, 医学部, 講師 (50133278)
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| Project Period (FY) |
1986 – 1988
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| Keywords | glycosphingolipids / gangliosides / alpha-sialocholesterol / alpha-sialoglyceride / differentiation-induction / HL-60 / シアロコレステロール / シアログリセリド |
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| Research Abstract |
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
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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
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