Resveratrol, a natural product derived from grapes, is a new inducer of differentiation in human myeloid leukemias.
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 microM, 4 days) alone inhibited the growth in liquid culture of each of the 6 cell lines. Resveratrol (10 microM) enhanced the expression of adhesion molecules (CD11a, CD11b, CD18, CD54) in each of the cell lines except for Kasumi-1. Moreover, resveratrol (25 microM, 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 microM) 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 microM, 3 days), the binding activity of nuclear factor-kappaB (NFkappaB) protein was suppressed. Eight of 19 samples of fresh acute leukemia cells reduced NBT after exposure to resveratrol (20 microM, 4 days). Taken together, these findings show that resveratrol inhibits proliferation and induces differentiation of myeloid leukemia cells.
Asou
Hiroya
H
Department of Molecular Oncology, Research Institute for Radiation Biology & Medicine, Hiroshima, Japan. asobu@hiroshima-u.ac.jp
Koshizuka
Kozo
K
Kyo
Taiichi
T
Takata
Noboru
N
Kamada
Nanao
N
Koeffier
H P
HP
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D027843:Vitis / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D013267:Stilbenes; D013481:Superoxides; D014212:Tretinoin; D000077185:Resveratrol