期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 247, 期 1-2, 页码 55-60出版社
SPRINGER
DOI: 10.1023/A:1024192719178
关键词
mesenchymal stem cells; retinoic acid; leukemia treatment; hemopoiesis; cdk inhibitors; p27(Kip1); p16(INK4A)
类别
The importance of bone marrow mesenchymal stem cells in hemopoiesis has been definitely demonstrated. Thus, their impairment might cause profound alteration on production and maturation of blood cells. In the present paper, we investigated, for the first time, the effect of retinoic acid, an important antileukemic molecule, on the proliferation of primary cultures of human bone marrow mesenchymal stem cells. We demonstrated that retinoic acid, at a pharmacological concentration, hampers strongly the growth of the cells, without inducing osteoblastic differentiation. The analysis of cell division cycle machinery showed that the antiproliferative effect is associated with (i) the up-regulation of two cyclin-dependent kinase inhibitors, namely p27(Kip1) and p16(INK4A), and (ii) the down-regulation of cyclin-dependent kinase 2 activity and pRB phosphorylation. The reported findings represent novel insights into the antileukemic effects of the drug and contribute in clarifying the molecular mechanism of its pharmacological activity.
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