tea prevents cancer
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Increased Concentration of CatechinsFollowing Black Tea Consumption
Plasma Levels(nmol/L)
Urinary Excretion(nmol/h)
Fecal Excretion(mol)
Epigallocatechin
Epicatechin
Epigallocatechin
Gallate
Epicatechin Gallate
Warden BA, et al. J Nutr 2001;131:1731-1737
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Epidemiological Studies ofTea and Cancer
Ecologic, case-control and cohort studieshave been performed.
Many performed as secondary analyses.
Little information on precision of tea intake.
Several cancer sites investigated: bladder andurinary tract, breast, colon and rectum,esophagus, kidney, liver, lung, nasopharynx,pancreas, stomach and uterus (with mixedresults).
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Recent Epidemiological Studies of TeaAnd Gastric/Stomach Cancer
Country (Tea type) Study Type Risk/Association Reference
China(green tea)
India(unknown)
Japan(green tea)
Japan(green tea)
Japan(green tea)
China(unknown**)
Japan(green tea)
Japan(green tea)
Case-control
Case-control
Prospectivecohort
Prospectivecohort
Prospectivecohort
Nested case-control
Prospectivecohort
Nested case-control
Decrease
Decrease
No association
No association*
No association
Decrease
Decrease***
Setiawan2001
Rao 2002
Tsubono
2001
Hoshiyama 2002
Fujino 2002
Sun 2002
Sasazuki 2004
Hoshiyama 2004
* Deaths **Urinary polyphenols/metabolites ***distal gastric, women only
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Effects of Tea on Human Oral Precancerous
Lesions
A double-blind intervention trial of 59 patients withoral mucosa leukoplakia
Twenty-nine patients received tea administeredorally and topically; 30 patients received placebotreatment
After 6 months, the size of oral lesion decreased in38% of the treated group and in 10% of the placebogroup; the lesion increased in 3.4% of the treatedgroup and in 6.7% of the placebo group
The incidence of micronucleated exfoliated oralmucosa cells in the treated group (0.54%) was lowerthan the control group (1.13%)
Li et al. Proc. Soc. Expr. Biol. Med. 220: 218-224, 1999.
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Effect of Increased Tea Consumption on
Oxidative DNA Damage Among Smokers
A phase II randomized controlled tea intervention trial (4 cups/d) ofdecaffeinated green or black tea among smokers over a 4-mo period.
143 heavy smokers, aged 18-79 y, were randomized to drink eithergreen or black tea or water.
Plasma and urinary levels of catechins rose significantly in the greentea group compared with the other two groups.
Significant decrease in urinary 8-OHdG (-31%) after 4 mo of drinkingdecaffeinated green tea (P = 0.002).
No change in urinary 8-OHdG was seen among smokers assigned to theblack tea group.
Hakim IA, et al. J Nutr. 2003; 133:3303S-3309S.
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Tea and Cancer Prevention
Camellia Sinensis
Yang, CS. Personal Communication
SkinLiver
Colon
Oral
Esophagus
LungStomach
ProstateMammary
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Results of Animal Studies With Tea
110Lung
36Breast
01Prostate
01Bladder
07Liver
310Intestine/Colon
05(Fore)stomach
13Esophagus
02Oral
513Skin
Not ProtectiveProtectiveOrgan Site
Number of Studies
Yang CS. Personal Communication
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The TRAMP MouseTransgenic Adenocarcinoma of Mouse Prostate (TRAMP) animal model
that express the oncogene SV40 T antigen specifically in the epithelium ofthe prostate.
Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion ofgreen tea polyphenols. Gupta et al. PNAS 2001;98:10350-10355.
100
50
0
30 Weeks2418126
metastasis
neoplasia
hyperplasia
puberty
TRAMP: A Model for Prostate Cancer Progression
Greenberg et al. (Found on TRAMP webpage)
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Reactive Oxygen Species
EndoplasmicReticulum
Mitochondrion
O2 H202 OH
Damage DNA,RNA
Oxidize Proteins
(enzymes, histones)
Oxidize LipidsActivate Cell
Suicide
TEAX
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Biological Activities of TeaPolyphenols
Induce Phase I and Phase II enzymes
Inhibit cell proliferation and induce apoptosis
Several effects on cell signaling pathways (e.g.,cyclooxygenase)
Inhibit angiogenesis and invasion
Inhibit DNA methyltransferase activity
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NF-B Metastasis(MMPs, cell adhesionmolecules,
cell surface proteases)
Angiogenesis
(Cox-2, NOS, VEGF)
Proliferation
(c-myc, cyclin D1, gro
cytokines [IL-2, -6])
Oncoproteins (Her-2/neu, Ras)
IKK activation
CK2 induction
IBIB
Activation and Roles of NF-Activation and Roles of NF-B in OncogenesisB in OncogenesisAltered cytokine production
NF-B
nfkb gene amplif.,
rearrangement
Survival(Bcl-xL, A1/Bfl-1,
IEX-1L, IAP1, IAP2)Mutations in IB genesCo-acting factors
(AP-1, AhR,
c/EBP, p300)
Modifications(phosphorylation,
acetylation)
EGCG
[Proteasome]
DEX
Sonenshein GE.Personal Communication
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Tea Polyphenol Epigallocatechin-3-Gallate
Inhibits DNA Methyltransferase Activity
Cancer Res. 63 22 : 2003
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D3-1 cells, DMBA-transformed MCF-10F mammary
epithelial cells
Human chip microarray (7,500 genes developed by
GenomicTree, Inc, Korea)
Dose: 60 g/ml EGCG (dissolved in DMSO) orequivalent volume of DMSO, as control
Time points: 2, 7, and 24 hrs Experiment performed twice, each time in duplicate
Microarray Analysis to Identify Genes
Responding to EGCG Treatment in Breast
Cancer Cells
Sonenshein GE.Personal Communication
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1 2 3 4 1 2 3 4
0.37 0.36 0.42 0.61 0.17 0.25 0.39 0.3
0.91 1.32 0.46 0.48 0.4 0.94 0.57 0.460.79 0.80 0.46 0.48 0.36 0.51 0.36 0.3
0.57 0.91 0.51 0.46 0.27 0.58 0.48 0.45
0.70 0.90 1.01 0.85 0.41 0.93 0.52 0.48
0.74 0.93 0.46 0.64 0.31 0.56 0.44 0.37
0.95 1.37 0.56 0.69 0.2 0.55 0.26 0.23
0.65 0.77 0.73 0.72 0.4 0.67 0.62 0.49
0.57 0.67 1.51 0.01 0.09 0.46 0.13 0.11
1.05 0.84 0.93 1.09 1.04 0.95 0.61 0.69
0.70 1.02 0.36 0.59 0.17 0.6 0.25 0.21
0.92 0.80 1.00 0.31 0.46 0.74 0.47 0.42
0.85 0.95 0.57 0.53 0.5 0.84 0.52 0.45
0.97 1.13 0.49 0.43 0.43 0.85 0.45 0.37
0.87 1.08 0.49 0.84 0.55 0.91 0.65 0.5
0.89 1.00 0.35 0.37 0.43 0.82 0.52 0.46
0.87 1.06 0.51 0.49 0.36 0.81 0.66 0.47
0.92 0.85 0.57 0.59 0.43 0.72 0.52 0.43
0.87 0.87 0.34 0.53 0.48 0.75 0.47 0.44
0.79 0.91 1.42 2.03 0.39 0.84 0.56 0.5
2.31 2.12 0.49 0.53 0.75 0.91 1 0.51.31 1.51 0.95 1.00 1.9 2.05 2.43 2.36
1.25 1.43 1.62 1.43 2.08 1.88 2.17 2.22
1.26 1.44 1.37 2.14 1.88 2.01 2.02 2.6
1.21 1.24 1.08 1.45 1.93 1.53 1.6 1.56
1.32 1.75 0.94 1.22 1.5 2.3 0.71 0.78
2 hours 7 hours
1 2 3 4
0.14 0.36 0.31 0.5 0.003
0.17 0.55 0.37 0.44 0.0050.32 0.64 0.3 0.35 0.005
0.24 0.44 0.49 0.47 0.002
0.33 0.62 0.32 0.45 0.004
0.28 0.52 0.48 0.48 0.002
0.28 0.73 0.39 0.45 0.011
0.31 0.52 0.47 0.6 0.003
0.08 0.47 0.4 1 0.075
0.65 0.46 0.47 0.45 0.002
0.2 0.63 0.28 1 0.082
0.44 0.76 0.43 0.49 0.009
0.4 0.79 0.43 0.52 0.014
0.37 0.83 0.45 0.5 0.020
0.36 1.02 0.38 0.43 0.065
0.4 0.77 0.49 0.57 0.011
0.39 0.85 0.51 0.55 0.022
0.5 0.73 0.57 0.65 0.004
0.94 0.75 0.67 0.63 0.035
0.71 0.83 0.72 0.81 0.005
1.03 0.91 0.54 0.6 0.1481.7 1.51 1.39 1.37 0.007
1.84 1.53 1.47 1.44 0.008
1.82 1.56 1.77 1.75 0.001
2.11 2.69 2.11 2.08 0.003
5.27 2.31 2.22 2.96 0.054
p value
24 hoursUNIQID AND GENE NAME
AI003699 LIM and SH3 protein 1
AA099134 Hypoxia up-regulated 1AA181307 aryl hydrocarbon receptor
AA520985 rab3 GTPase-activating protein
AA488674 myeloid cell leukemia sequence 1
H50344 tight junction protein 1
AA464532 thrombospondin 1a2
AA053886 SREBP 2
AA995560 protein tyrosine phosphatase
AA872383 metallothionein 1E (functional)
AI031571 epithelial cell transforming sequence
R45056 Human clone 23721 mRNA sequence
AA151214 Ras-GTPase activating protein
N69204 chromosome segregation 1
W69399 H1 histone family, member 0
AI865149 karyopherin alpha 6
R59621 LanC (bacterial lantibiotic synthetase c
H92201 nucleosome assembly protein 1-like 4
AA773461 chord domain-containing protein 1
W46972 solute carrier family 20
AA598794 connective tissue growth factorAA916325 aldo-keto reductase family 1,C3
AI924357 aldo-keto reductase family 1,C2
R93124 aldo-keto reductase family 1,C1
AI023541 carbonic anhydrase IX
T54298 PPAR(gamma) angiopoietin related
Identification of Genes Affected by EGCG Treatment in D3-1Identification of Genes Affected by EGCG Treatment in D3-1
Breast Cancer CellsBreast Cancer Cells
24 h samples
Sonenshein GE.Personal Communication
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AhR (AA181307)*
CSE-1 (N69204 )*
CTGF (AA598794)*
Heat shock protein 10kD (AA448396)
Prefoldin (AI682392)
ECTS (AI031571)*
DMSO
EGCG
24h
TGF (R36467)BMP6 (AA424833)
GST (A4(aa152374))
Angiopoietin (T54298)*
PTP3 (AA995560)*
Thrombospondin (AA464532)*
WISP-1 (AI473336)
GAPDH
Ring finger protein (AA402960)
AhR (AA181307)
28S
18S
RT-PCR
Northern
RT-PCR and Northern Blot Analysis Confirms Affects of EGCG
on Expression of Several Genes
Genes Regulated by 24 h EGCG
BMP6 AhR
WISP-1 CTGF
PPAR ECTSGST HSP10
Sonenshein GE.Personal Communication
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Summary
Green, black and oolong teas are differentiated bytea manufacturing processes
Teas are rich in polyphenols, e.g., catechins,theaflavins, thearubigens
Epidemiological studies show inconsistentevidence for the association between teaconsumption and reduced risk of cancer
Preclinically, tea frequently inhibits colon,esophageal, liver, lung and skin tumorigenesis
Tea and tea polyphenols may have multiple sites ofaction