Resveratrol, a natural dietary phytoalexin, possesses similar properties to hydroxyurea towards erythroid differentiation
Resveratrol, a natural dietary phytoalexin, possesses similar properties to hydroxyurea towards erythroid differentiation
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DOI：
10.1046/j.1365-2141.2001.02746.x
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发表时间：
2001-05-01
影响因子：
6.5
通讯作者：
Garel, MC
中科院分区：
文献类型：
--
作者：
Rodrigue, CM;Arous, N;Garel, MC
白藜芦醇是一种天然的膳食多酚，它被认为与红酒的心脏保护作用以及素食者和东方人的乳腺癌和前列腺癌的低发病率有关。这种化合物抑制核糖核苷酸还原酶，羟基脲也是第一种用于治疗镰状细胞病的治疗剂。使用人红细胞白血病K562细胞系作为体外模型，我们在这里发现，50 μ mol/l的白藜芦醇诱导K562细胞的血红蛋白生成（7倍）比500 μ mol/l的羟基脲（3.5倍）高。这种红系分化与细胞增殖的剂量和时间依赖性抑制有关，与p21 mRNA表达的等效增加有关，但白藜芦醇处理的细胞p21蛋白水平的增加（6倍）高于羟基脲处理的细胞（1.5倍）。我们还发现，50 μ mol/l的白藜芦醇和25 μ mol/l的羟基脲对大多数镰状细胞患者的培养红细胞祖细胞的胎儿血红蛋白合成有不同但相似的促进作用。这些诱导与红系爆发形成单位克隆数的可变减少有关，但不相关。综上所述，这些结果表明白藜芦醇在镰状细胞病治疗中值得进一步研究。
Resveratrol, a natural dietary polyphenol, has been postulated to be implicated in the cardioprotective effect of red wine and the low incidence of breast and prostate cancers among vegetarians and orientals respectively. This compound inhibits ribonucleotide reductase as does hydroxyurea, the first therapeutic agent used in the treatment of sickle cell disease. Using the human erythroleukaemic K562 cell line as an in vitro model, we show here that 50 mu mol/l of resveratrol induced a higher haemoglobin production (sevenfold) in K562 cells than 500 mu mol/l of hydroxyurea (3.5-fold). This erythroid differentiation was Linked to a dose- and time-dependent inhibition of cell proliferation associated with an equivalent increased expression of p21 mRNA, but with a higher increased level of p21 protein (sixfold) for cells treated with resveratrol than for those treated with hydroxyurea (1.5-fold). We also show that 50 mu mol/l of resveratrol and 25 mu mol/l of hydroxyurea induced variable but similar inhancements of fetal haemoglobin synthesis in cultured erythroid progenitors for the majority of the sickle cell patients studied. These inductions were linked to, but not correlated with, a variable decrease in erythroid burst-forming unit clone number. Taken together, these results show that resveratrol merits further investigations in sickle cell disease therapy.