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Quercetin inhibits the growth of leukemic progenitors and induces the
expression of transforming growth factor-beta 1 in these cells
LM Larocca, L Teofili, S Sica, M Piantelli, N Maggiano, G Leone and FO Ranelletti
Istituti di Anatomia Patologica, Universita Cattolica del Sacro Cuore,
Roma, Italy.
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.
Volume 85,
Issue 12,
pp. 3654-3661,
06/15/1995
Copyright © 1995 by The American Society of Hematology
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