Carcinogenesis, Vol 18, 451-456, Copyright © 1997 by Oxford University Press
R Yu, JJ Jiao, JL Duh, K Gudehithlu, TH Tan and AN Kong
Green tea polyphenols, major constituents of green tea, are potent
chemopreventive agents in a number of experimental models of cancer in
animals. The mechanisms of cancer protection by these agents are not clear,
but may involve modulation of the enzyme systems responsible for the
detoxification of chemical carcinogens. The present studies show that a
green tea polyphenol extract (GTP) induces chloramphenicol
acetyltransferase (CAT) activity in human heptoma HepG2 cells transfected
with a plasmid construct which contains an antioxidant- responsive element
(ARE) and a minimal glutathione S-transferase Ya promoter linked to the CAT
reporter gene. This indicates that GTP stimulates the transcription of
Phase II detoxifying enzymes through the ARE. To explore the upstream
signaling pathways leading to gene expression, we studied the involvement
of the mitogen-activated protein kinases (MAPKs) extracellular
signal-regulated kinase 2 (ERK2) and c- Jun N-terminal kinase 1 (JNK1).
Potent activation of ERK2 was seen following treatment of HepG2 cells with
different concentrations of GTP. Similar to ERK2, JNK1 was also strongly
activated by treatment with GTP, although to a lesser extent and in a
different dose-dependent fashion. Kinetic studies revealed that GTP
activation of JNK1 was delayed and sustained, whereas ERK2 activation was
rapid and transient. Furthermore, GTP treatment also increased mRNA levels
of the immediate- early genes c-jun and c-fos, as determined by reverse
transcriptase- coupled polymerase chain reaction. Taken together, these
studies provide insights into the action of GTP and suggest that the
stimulation MAPKs may be the potential signaling pathways utilized by GTP
to activate ARE-dependent genes.
ARTICLES
Activation of mitogen-activated protein kinases by green tea polyphenols: potential signaling pathways in the regulation of antioxidant-responsive element-mediated phase II enzyme gene expression
Department of Pharmaceutics and Pharmacodynamics, College of Pharmacy, University of Illinois, Chicago 60612, USA.
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