4-メチルウンベリフェロンによるHL-60細胞の分化過程におけるアポトーシスの誘導および生体高分子生合成の変化
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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.