Rodrigue C M, Arous N, Bachir D, Smith-Ravin J, Romeo P H, Galacteros F, Garel M C
INSERM U474, Maternité Port-Royal, ICGM Cochin, Paris, France.
Br J Haematol. 2001 May;113(2):500-7. doi: 10.1046/j.1365-2141.2001.02746.x.
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 micromol/l of resveratrol induced a higher haemoglobin production (sevenfold) in K562 cells than 500 micromol/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 micromol/l of resveratrol and 25 micromol/l of hydroxyurea induced variable but similar enhancements 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.
白藜芦醇是一种天然膳食多酚，据推测它分别与红酒对心脏的保护作用以及素食者和东方人乳腺癌和前列腺癌发病率较低有关。该化合物与羟基脲一样能抑制核糖核苷酸还原酶，羟基脲是用于治疗镰状细胞病的第一种治疗药物。我们以人红白血病K562细胞系作为体外模型，在此表明，50微摩尔/升的白藜芦醇在K562细胞中诱导产生的血红蛋白量（增加了7倍）高于500微摩尔/升的羟基脲（增加了3.5倍）。这种红系分化与细胞增殖的剂量和时间依赖性抑制有关，同时伴随着p21 mRNA表达等量增加，但白藜芦醇处理的细胞中p21蛋白增加水平更高（增加了6倍），而羟基脲处理的细胞中p21蛋白增加水平为1.5倍。我们还表明，对于大多数所研究的镰状细胞病患者，50微摩尔/升的白藜芦醇和25微摩尔/升的羟基脲在培养的红系祖细胞中诱导了胎儿血红蛋白合成的不同但相似的增强。这些诱导作用与红系爆式形成单位克隆数的不同程度减少有关，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。
