Christene Guirgess

Polyphenols in Tea and the Reduction of Cancer

Abstract
Many polyphenols have demonstrated anticarcinogenic activities in animals. In
this paper, Tea catechins will be used as an example to illustrate current
research in this area. In most of the studies, the inhibitory activity of tea could be
demonstrated when tea preparations were given either during or after carcinogen
treatment periods. Different types of tea were used such as black tea, green tea
and decaffeinated tea. The most effective tea treatment was demonstrated by
green tea and decaffeinated tea; black tea was effective, although it was weaker
than green tea. The mechanisms of how these treatments work are not yet
known, but it is most likely attributed to the biochemical activity of tea
polyphenols, which include antioxidative activities and inhibition of cell
proliferation (Yang et al., 1998).

Introduction
Green tea, a popular beverage consumed around the world, has been shown to
possess cancer prevention effects in a wide range of target organs in rodent
cancer models. Studies have shown that men who consume tea consistently may
have a lower risk of prostate cancer. In the Japanese and Chinese cultures, who
regularly consume tea, especially green tea, have one of the lowest occurrences
of prostate cancer in the world. Chemoprevention studies for humans should be

studied in animal models that closely resemble human disease. The greatest
significance of these studies is that animal cancer is in their natural tissues and
progresses through multiple stages, as is the case in humans.
Studies, although not conclusive, have shown the protective role of green tea
against prostate cancer, lung cancer, skin cancer, esophageal cancer and gastric
cancer development. Recent studies have shown that green tea and its
polyphenols convey inhibitory effects on the activity of the many enzymatic,
metabolic and signaling pathways that have significance to cancer development
and progression. Skin cancer is the most common form of cancer affecting
humans; ultraviolet radiation is the primary factor that contributes to the risk of
skin cancer. Current methods used in the prevention of skin cancer are the
application of sunscreens and the avoidance of the sun at peak times. This does
not seem to be enough in protecting the skin against the ultraviolet radiation.
Recently, research has shown the beneficial components of green tea and its
capability in the prevention of skin cancer.

Studies on Animals
The major anti-cancer components of tea are believed to be the tea polyphenols,
which are known as catechins. The polyphenols in green tea are classified as (-)epigallocatechin gallate (EGCG), (-)-epigallocatehin (EGC), (-)-epicatechin-3gallate (ECG), and (-)-epicatechin (EC). The structures of polyphenols are shown
in Figure 1 (Gupta et al., 2001).

Figure 1. Structures of major polyphenols in green tea.

In a study conducted by (Katiyar, 2007), topical green tea polyphenols were

administered to mice; the results showed significant protection against local and
systemic models of contact hypersensitivity. Similar effects were also shown
when an aqueous solution extracted from the green tea was given to the mice as
their primary drinking source. EGCG was the main component in the green tea
polyphenols that was effective in the prevention of UVB-induced suppression of
contact hypersensitivity. The administration of green tea polyphenols in the

drinking water of mice greatly reduced UVB-induced tumor development (Meeran

et al., 2009). Both systemic and topical administration of green tea polyphenols
and EGCG were found to protect against the UV-induced sunburn response, UVinduced immunosuppression and photoaging of the skin (Khan, 2008).
Many epidemiological studies have supported the correlation between green tea
polyphenol consumption and the prevention of skin cancer. These mechanisms,
however, need to be evaluated and attested on animal models and humans to
fully gain an understanding of the preventive effects of polyphenols contained in
tea against human skin cancer.

Reduction of Tumorigenesis in the Lungs

Tea extracts and tea polyphenols inhibit tumorigenesis in a variety of different
animal organs. Green tea infusion, as the sole source of drinking fluid for mice,
drastically reduced N-nitrosodiethylamine (NDEA) - induced lung tumor by (36 to
44%) and tumor duplication by (44 to 60%) (Gupta et al., 2001) The results are
even more staggering when looking at the effects of decaffeinated green tea
(DGT) or black tea which contain theaflavin monomers. The inhibition of lung
tumorigenesis caused by 4-methylnitrosamino-1-(3-pyridil)-1-butanone (NNK) on
multiplicity went from 65 to 85% and tumor occurrence was lessened 14 to 30%
inhibition (Gupta et al., 2001). Tea preparations were effective when given to the
mice before or after cancer treatment. Treatment with DGT, starting 2 weeks
before injection and continuing to one week after, was more effective in reducing
tumor occurrence by (56%) than treatment starting 2 weeks after the injection

(31%). When tea was given to the mice directly after treatment for 1 week, the
occurrence was reduced (20%). Even if DGT was given 5 weeks after treatment
there was a reduction in occurrence by (54%) (Gupta et al., 2001).

Reduction of Tumorigenesis in the Esophagus

The esophageal tumor incidence and multiplicity were reduced by approximately
70% when administering 0.6% of DGT to male rats via their drinking fluid Nnitrosmethyl-benzylamine (NMBzA) treatment (Gupta et al., 2001). Esophageal
papilloma incidence and multiplicity were reduced by approximately 50% if given
after NMBzA treatment. When rats received 0.9% regular green tea, there was
an approximate 60% reduction in volume per tumor (Gupta et al., 2001).

Research on mice for prostate cancer

For many experiments, the 20 mice of 8 weeks of age were equally divided into
two groups. A solution of 0.1% GTP (epigallocatechin-3-gallate (62%),
epicatechin-3-gallate (24%) epigallocatechin (5%), epicatechin (6%), caffeine
infused tap water was supplied every Monday, Wednesday, and Friday as the
only source of drinking fluid for 24 weeks to the mice (Gupta et al., 2001). As for
the control mice, they were supplied with the same tap water throughout the
experiments. All of the 10 water fed mice developed severe prostate cancer. In
contrast, only 3 of the 10 GTP infused water-fed mice developed visible tumors.
In repeating this experiment, the 10 control mice developed malignant and visible
tumors. Compare that to the GTP infused mice only 4 out of the 10 had visible

tumors (Gupta et al., 2001). It is important to remark the invasiveness of the

prostate cancer was much less invasive than the control group. At the conclusion
of the experiment at 32 weeks of age, the results were as follows: The control
group - all 10 mice - showed 100% invasive tumors which also metastasized to
lymph, lungs, liver and bone. In comparison, the GTP infused mice showed a
sharp contrast in results; none of the tumors metastasized to any of the other
organs. To assess the progression of GTP infusion in mice, measurements were
first taken by MRI. MRI results indicated that water-fed mice showed the
presence of prostate tumor at 20 weeks, at 30 weeks the water fed-mice were
tested again for the growth of the tumor and the results showed that there was a
full development of tumor. Comparing these results to the results of the green tea
infused mice showed that there was a significant prevention or delay in prostate
cancer development at 20 weeks of age (44% inhibition) and in 30 weeks of age
(42% inhibition). Here are some drastic results from GT infused water-fed mice.

Figure 2. (A) Photograph of a typical GU apparatus of TRAMP mice exhibiting

hyper-proliferation. (B) GU apparatus of TRAMP mice with 0.1% infused for 24
weeks. A marked decrease in GU weight and volume was observed in TRAMP
mice after GTP infusion. (C) Histologic examination of a typical TRAMP mouse
prostate at 32 weeks of age revealed moderately differentiated neoplastic cells
with extensive cribriform structures, marked thickening, remodeling, and
hypercellularity of the fibromuscular stroma. (D) GTP infusion (0.1%, wt/vol) to
TRAMP mice resulted in a marked reduction in epithelial stratification and
cribriform structures, and the glands remained simple without epithelial
thickening or surface complexity (Gupta et al., 2001).

Gastric Cancer in Women

In researching gastric cancer in women the subjects were asked a questionnaire
including the green tea consumption of almost none, 1-2, 3-4 days per week; 1-2,
3-4 or 5 or more cups per day for those consume almost daily for 5-7 days (Yang
et al., 1997). In this study, the reduction of gastric cancer in relation to the
consumption of green tea was evident in women. This observation was more

notable when the tumor was localized to the distal stomach. There was a
decreased risk of gastric cancer in women after adjustment for potential factors.
The relative risk was 0.51 in the highest category of green tea consumption (5 or
more cups per day versus 1 cup per day), further evidence that tea consumption
has anti-carcinogenic effects (Yang et al., 1997)

Conclusion
Any delay or progression in prostate cancer by the use of chemoprevention is an
important health benefit. To ensure efficacy of the chemopreventative agents,
they should first be modeled out on mice that mimic human disease before they
can be recommended for use on humans. The most significant result that were
found is that the oral infusion of a human achievable dose of tea resulted in a
significant inhibition in the growth of prostate cancer (Gupta et al., 2001). Studies
have shown that the green tea and epigallocatechin-3-gallate inhibit the growth of
human prostate cancer cells. The findings on green tea polyphenols and the
prevention of cancer all seem to be consistent across multiple studies in animals.
They all show that EGCG, the main component in green tea polyphenols,
protects against immunosuppression. This general conclusion in various studies
highly suggests the beneficial nutrients provided by green tea. Similar findings
were concluded in the human model studies. More extensive studies have been
evaluated using rats because they are easily available and much easier to
control. In order to gain full understanding of the preventive effects of green tea
polyphenols, extensive studies need to be conducted on a larger population of

humans. Humans, however, are not all the same in genetic makeup or lifestyle
so the results may be conflicting and influenced by many external factors.

Literature Cited
Chung S. Yang; Mao-Jung Lee; Laishun Chen; Guang-Yu Yang. Polyphenols As
Inhibitors of Carcinogenesis Environmental Health Perspectives, Vol. 105,
Supplement 4 (Jun., 1997), pp. 971-976Publisher(s): Brogan & Partners
Katiyar, S.K. UV-induced immune suppression and photocarcino genesis:
chemoprevention by dietary botanical agents. Cancer Letters 225 (2007a), 1-11
Khan, N., F. Afaq and H. Mukhtar. Cancer chemoprevention through dietary
antioxidants: progress and promise. Antioxidants & Redon Signaling 10 (2008),
475-510.
Meeran S.M., S. Akhtar and S.K. Katiyar. Inhibition of UVB-induced skin tumor
development by drinking green tea polyphenols is mediated through DNA repair
and subsequent inhibition of inflammation. Journal of Investigative Dermatology
129 (2009), 1258-1270.

Sanjay Gupta; Kedar Hastak; Nihal Ahmad; Jonathan S. Lewin; Hasan Mukhtar
Inhibition of Prostate Carcinogenesis in TRAMP Mice by Oral Infusion of Green
Tea Polyphenols Proceedings of the National Academy of Sciences of the United
States of America, Vol. 98, No. 18 (Aug. 28, 2001), pp. 10350-10355

Shizuka Sasazuki; Manami Inoue; Tomoyuki Hanaoka; Seiichiro Yamamoto;

Tomotaka Sobue; Shoichiro Tsugane for the JPHC Study Group
Green Tea Consumption and Subsequent Risk of Gastric Cancer by Subsite:
The JPHC Study Cancer Causes & Control, Vol. 15, No. 5 (Jun., 2004), pp. 483491
Suminori Kono and Tomio Hirohata
Nutrition and Stomach Cancer Cancer Causes & Control
Vol. 7, No. 1 (Jan., 1996), pp. 41-55