Catechin, a green tea component, rapidly induces apoptosis of myeloid leukemic cells via modulation of reactive oxygen species production in vitro and inhibits tumor growth in vivo.
OBJECTIVE
The aim of this study was to investigate the possibility of green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG) as a novel therapeutic agent for the patients with myeloid leukemia.


METHODS
We investigated the effects of EGCG on the induction of apoptosis in leukemic cells in vitro and in vivo. We further examined the molecular mechanisms of EGCG-induced apoptosis in myeloid leukemic cells.


RESULTS
EGCG rapidly induced apoptotic cell death in retinoic acid (RA)-resistant acute promyelocytic leukemia (APL), UF-1 cells within 3 h. EGCG induced apoptosis in UF-1 cells was in association with the loss of mitochondrial transmembrane potentials (Deltapsim) and activation of caspase-3 and -9. Elevation of intracellular reactive oxygen species (ROS) production was also demonstrated during EGCG-induced apoptosis of UF-1 as well as fresh myeloid leukemic cells. In NOD/SCID mice transplanted with UF-1 cells, EGCG effectively inhibited tumor growth in vivo, and the number of mitoses among the cells significantly decreased in comparison to that of control mouse cells.


CONCLUSIONS
In summary, EGCG has potential as a novel therapeutic agent for myeloid leukemia via induction of apoptosis mediated by modification of the redox system.
Nakazato
Tomonori
T
Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Ito
Keisuke
K
Miyakawa
Yoshitaka
Y
Kinjo
Kentaro
K
Yamada
Taketo
T
Hozumi
Nobumichi
N
Ikeda
Yasuo
Y
Kizaki
Masahiro
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D017382:Reactive Oxygen Species / Q000378:metabolism; D014183:Transplantation, Heterologous
D017382:Reactive Oxygen Species; D002392:Catechin