We previously showed that
quercetin (3,3',4',5,7
pentahydroxyflavone) inhibits in a dose-dependent manner the growth of acute
leukemias and is able to enhance the antiproliferative activity of
cytosine arabinoside. We show here that
quercetin inhibits the clonogenic activity of 20 of 22 acute
leukemias (AL; 4 M1-AML, 3 M2-AML, 2 M3-AML, 3 M4-AML, 3 M5-AML, and 7 ALL). In the present report, we show that the induction of
transforming growth factor-beta 1 (TGF-beta 1) in leukemic blasts is one of the growth-inhibitory mechanisms of
quercetin in these cells. This observation was supported by the following data. (1)
Quercetin-sensitive leukemic blasts, when treated with
quercetin, secrete large amounts of
TGF-beta 1 in the medium and show positivity for
TGF-beta 1-immunoreactive material in the cytoplasm. (2) At a concentration of 8 mumol/L, antisense
TGF-beta 1 oligonucleotides prevent the growth-inhibitory action of
quercetin. (3) Anti-
TGF-beta 1 neutralizing
monoclonal antibodies can prevent almost completely the growth-inhibitory activity of
quercetin. The analysis of
quercetin-resistant cases confirmed as well the central role of
TGF-beta 1 in the growth-inhibitory activity of
quercetin. In conclusion,
quercetin can act as a
cytostatic agent for leukemic cells by modulating the production of
TGF-beta 1.