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Resveratrol, a natural dietary phytoalexin, possesses similar properties to hydroxyurea towards erythroid differentiation
Author(s) -
Rodrigue Christelle M.,
Arous Nicole,
Bachir Dora,
SmithRavin Juliette,
Romeo PaulHenri,
Galacteros Frédéric,
Garel MarieClaude
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02746.x
Subject(s) - resveratrol , ribonucleotide reductase , phytoalexin , biology , k562 cells , hydroxycarbamide , cell culture , cell growth , cell , fetal hemoglobin , endocrinology , medicine , pharmacology , biochemistry , fetus , chemotherapy , pregnancy , genetics , gene , protein subunit
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 μmol/l of resveratrol induced a higher haemoglobin production (sevenfold) in K562 cells than 500 μmol/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 μmol/l of resveratrol and 25 μmol/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.