Resveratrol, a natural dietary phytoalexin, possesses similar properties to hydroxyurea towards erythroid differentiation

Resveratrol, a natural dietary polyphenol, has been postulated to be implic ated in the cardioprotective effect of red wine and the low incidence of br east and prostate cancers among vegetarians and orientals respectively. Thi s 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 th at 50 mu mol/l of resveratrol induced a higher haemoglobin production (seve nfold) in K562 cells than 500 mu mol/l of hydroxyurea (3.5-fold). This eryt hroid differentiation was Linked to a dose- and time-dependent inhibition o f cell proliferation associated with an equivalent increased expression of p21 mRNA, but with a higher increased level of p21 protein (sixfold) for ce lls treated with resveratrol than for those treated with hydroxyurea (1.5-f old). We also show that 50 mu mol/l of resveratrol and 25 mu mol/l of hydro xyurea induced variable but similar inhancements of fetal haemoglobin synth esis 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 to gether, these results show that resveratrol merits further investigations i n sickle cell disease therapy.