Induction of Apoptosis and Changes of Macromolecule Synthesis during Differentiation of HL-60 Cells by 4-methylumbelliferone

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概要

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• We have studied the effect of O-glycosylation inhibitors on the differentiation of human myeloid leukemia cell line, HL-60. O-glycosylation inhibitors used were both N-acetyl-α-D-galactosaminides as inhibitors for synthesis of mucin-type oligosaccharides of glycoproteins and β-D-xylosides as inhibitors for synthesis of glycosaminoglycans of proteoglycans. We have found that only 4-methylumbelliferyl-β-D-xyloside (MUX) among chemicals tested showed the differentiation-inducing activity to granulocyte-like cells, and that this activity was derived from its aglycon, 4-methylumbelliferone (4MU) [submitted for publication]. During this study, we have found that 4MU also induced apoptosis of HL-60 cells, judging from both the formation of apoptotic bodies and the DNA ladder formation in the agarose gel electrophoreic analysis of cellular DNA. The DNA ladder formation was observed after 1-2 days following a treatment with 4MU, and preceded the appearance of nitroblue tetrazolium (NBT) reducing activity. Moreover, we studied the effect of 4MU on the macromolecule synthesis of HL-60 cells. we have found that 4MU inhibited DNA synthesis, RNA synthesis, protein synthesis, glycoprotein synthesis and phospholipid synthesis to a similar extent. These results suggest that the primary target of the effect of 4MU may be a more common site in HL-60 cells such as energy metabolism, membranes, and so on. This study showed the possible use of 4MU for chemotherapy of leukemia by inducing differentiation or apoptosis.

• 東海大学の論文

著者

• Nishikawa Yoshihisa

  Department Of Applied Biochemistry Tokai University

• Takahashi Tetsuo

  Assistant Department Of Industrial Chemistry School Of Engineering

• Shibuya Yoshito

  Course Of Industrial Chemistry Graduate School Of Engineering

• NARA Mikiko

  Student, Course of Industrial Chemistry, School of Engineering

• FUKUOKA Akira

  Course of Industrial Chemistry, School of Engineering

• Nishikawa Yoshihisa

  Department Of Applied Biochemistry School Of Engineering Tokai University

• Fukuoka Akira

  Course Of Industrial Chemistry School Of Engineering

• Nara Mikiko

  Student Course Of Industrial Chemistry School Of Engineering

関連論文

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• Disruption of Mitochondria Is an Early Event during Dolichyl Monophosphate-induced Apoptosis in U937 Cells(Neurobiology)
• Effects of O-Glycosylation Inhibitors on the Differentiation of HL-60 Cells
• Remarkable Expression in the Colon Adenocarcinoma of Hmat-Xa, a Human Mannosyltransferase-Like Gene, That Is Homologous to Drosophila Gene GC15914
• The Improvement of the Homology Cloning Method for the Isolation of the Human Gene Involved in Lipid-linked Oligosaccharide Synthesis
• cDNA Cloning of the Putative Human β-1,4 Mannosyltransferase Gene which is Involved in Lipid-linked Oligosaccharide Synthesis
• Induction of Apoptosis and Changes of Macromolecule Synthesis during Differentiation of HL-60 Cells by 4-methylumbelliferone
• Analysis of Human Genomic DNA Transformants That Have Recovered from the Deffect of Lipid-Linked Oligosaccharide Synthesis in Mouse G258 Mutant
• From Glycobiology to Glycotechnology
• Remarkable Expression in the Colon Adenocarcinoma of Hmat-Xa, a Human Mannosyltransferase-Like Gene, That Is Homologous to Drosophila Gene GC15914
• Complementation of a Defect in the Asparagine-Linked Glycosylation of a Mouse FM3A Mutant G258 Cell Line by Spheroplast Fusion of a Human Mega YAC Clone 923f5

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