International Journal of Hematology

DOI: 10.1007/BF02982118 Pages: 528-533

Resveratrol, a Natural Product Derived from Grapes, Is a New Inducer of Differentiation in Human Myeloid Leukemias

1. Research Institute for Radiation Biology & Medicine, Department of Molecular Oncology

2. Cedars-Sinai Medical Center, UCLA School of Medicine, Division of Hematology/Oncology

3. Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

4. Hiroshima University Hospital, Division of Blood Transfusion

5. Hiroshima University

Correspondence to:
H. P. Koeffler
Tel: 082-257-5838
Fax: 082-256-7103
Email: asobu@hiroshima-u.ac.jp

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Abstract

A natural product, resveratrol (3,4,40-trihydroxy-trans-stilbene), a phytoalexin found in grapes and other food products, is known as a cancer chemopreventive agent. We studied the in vitro biological activity of this compound by examining its effect on proliferation and differentiation in myeloid leukemia cell lines (HL-60, NB4, U937,THP-1, ML-1, Kasumi-1) and fresh samples from 17 patients with acute myeloid leukemia. Resveratrol (20 μM, 4 days) alone inhibited the growth in liquid culture of each of the 6 cell lines. Resveratrol (10 μM) enhanced the expression of adhesion molecules (CD11a, CD11b, CD18, CD54) in each of the cell lines except for Kasumi-1. Moreover, resveratrol (25 μM, 4 days) induced 37% of U937 cells to produce superoxide as measured by the ability to reduce nitroblue tetrazolium (NBT). The combination of resveratrol (10 μM) and all-trans-retinoic acid (ATRA) (50 nM, 4 days) induced 95% of the NB4 cells to become NBT-positive, whereas <1% and 12% of the cells became positive for NBT after a similar exposure to either resveratrol or ATRA alone, respectively. In U937 cells exposed to resveratrol (25 μM, 3 days), the binding activity of nuclear factor-κB (NFκB) protein was suppressed. Eight of 19 samples of fresh acute leukemia cells reduced NBT after exposure to resveratrol (20 μM, 4 days). Taken together, these findings show that resveratrol inhibits proliferation and induces differentiation of myeloid leukemia cells.

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