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he term "Chemoprevention" is coined for cancer prevention and cancer
control by use of naturally occurring and/or synthetic compounds. The
occurrence of the disease may be completely prevented, blocked, or reversed.
This approach is promising because chemotherapy and surgery have not been
fully effective against the high incidence or low survival rate of most of
the cancers. In this regard, the naturally occurring antioxidants present
in the diet and beverages consumed by humans are receiving increasing
attention.
 Tea consumption in the world
is very high and ranks second to water consumption. Most tea consumed in
the world can be classified in two forms, green tea (approximately 20 percent)
and black tea (approximately 80 percent). Extensive studies from laboratories
over the last 10 years have verified cancer chemopreventive effects of a
polyphenol mixture derived from green tea against many animal tumor bioassay
systems. In these studies, oral consumption or topical application of green
tea polyphenols or its major constituent, epigallocatechin-3-gallate, has been
shown to offer protection against all stages of multistage carcinogenesis
that include initiation, promotion, and progression. A 1992 study by Wang
et al. has also shown that green tea consumption can inhibit the
growth of established skin papillomas in mice. Epidemiologic studies have
not provided conclusive results but tend to suggest that green tea may reduce
the risk associated with cancers of the bladder, prostate, esophagus, and
stomach.
Deciphering the molecular
mechanism by which green tea imparts the protective effects is important
because it may provide opportunities to interfere with cancer development
through administration of purified polyphenolic derivatives.
Green tea
appears to be potentially an ideal agent for chemoprevention because it
has the following characteristics:
Little or no adverse effects;
High efficacy against multiple sites;
Effectiveness at achievable dose levels;
Capability for oral consumption;
A known mechanism of action;
Low cost;
History of use by the human population; and
General human acceptance.
Cancer chemopreventive agents may
alter the regulation of cell cycle. Treatment with such agents may result in
cell cycle arrest, thereby reducing the growth and proliferation of cancerous
cells, and may also affect the malignant transformation. It has been suggested
that tumor growth depends on evasion of normal control mechanisms that
operate through a programmed deletion of cells (i.e., apoptosis).
o
further explore this theory, in 1997 N. Ahmad, D. K. Feyes, R. Agarwal,
H. Muktar, and A.-L. Nieminen of the School of Medicine, Case Western Reserve
University in Cleveland, OH set up an in vitro study to investigate
if green tea polyphenols and the major constituent, epigallocatechin-3-gallate,
induced apoptosis and perturbed cell cycle progression in carcinoma cells.
Since epigallocatechin-3-gallate is the major constituent present in green
tea polyphenols (approximately 50 percent, wt/wt), they performed all the
subsequent experiments with epigallocatechin-3-gallate.
As part of their ongoing large-scale
program on cancer chemoprevention through diatary constituents, the main aim
of the study was to elucidate the mechanism of antitumorigenic effect of
epigallocatechin-3-gallate, the major polyphenolic agent present in green
tea, and to determine if it directly affects the cell cycle regulation and
apoptosis. Apoptosis in recent years has become an important issue in biomedical
research. The life spans of both normal and cancer cells within a living
system are regarded to be substantially affected by the rate of apoptosis.
In addition, apoptosis is a discrete way of cell death different from
necrotic cell death and regarded to be an ideal way of cell elimination.
Thus, the chemopreventive agents which can modulate apoptosis may be able
to affect the steady-state cell population that are often useful targets in the
management and therapy for cancer.
In their study, Ahmad et al.
demonstrated that green tea polyphenols and their constituents resulted in an
induction of apoptosis in A431 cells. Important to note was the fact that
epigallocatechin-3-gallate resulted in the induction of apoptosis in all
carcinoma cells but not in the normal cells they examined. This selectivity,
if it can be observed in vivo at the desirable doses, will be of
great therapeutic importance. A vast variety of the chemotherapeutic agents
currently used in cancer therapy are thought to kill the cells by the
mechanisms other than apoptosis. This may not always be a preferable way of
cancer management. Ahmad et al.'s results showing the induction of
apoptosis by epigallocatechin-3-gallate is of importance because its treatment
of A431 cells did not cause any necrosis as evident from the confocal microscopy.
Moreover, the four different carcinoma cells used in their study had origins
from different body sites. This showed that epigallocatechin-3-gallate may
be useful against many, if not all, types of cancers. The demonstration of
induction of apoptosis by epigallocatechin-3-gallate is also important
because green tea is a well-consumed beverage worldwide and has shown
promising cancer chemopreventive effects in both laboratory experiments
and human epidemiologic studies.
The effect of epigallocatechin-3-gallate
in arresting the A431 cells in some phases of the cell cycle suggests the
possibility that green tea may also be useful for the control of cancer
growth. Based on their findings and on the extensive amount of laboratory
and epidemiology data available, Ahmad et al. suggested that
clinical trials with epigallocatechin-3-gallate are needed in a population
with high cancer risk.
- As reported in Journal of the National Cancer Institute,
Vol. 89, No. 24, December 17, 1997
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