Tea as another AA/PGE2 buster ...
Taka
Effects of purified green and black tea polyphenols on cyclooxygenase-
and lipoxygenase-dependent metabolism of arachidonic acid in human
colon mucosa and colon tumor tissues.
Hong J, Smith TJ, Ho CT, August DA, Yang CS.
Laboratory for Cancer Research, College of Pharmacy, Rutgers, The
State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ
08854-8020, USA.
The effects of green and black tea polyphenols on cyclooxygenase
(COX)- and lipoxygenase (LOX)-dependent arachidonic acid metabolism in
normal human colon mucosa and colon cancers were investigated. At a
concentration of 30 microg/mL, (-)-epigallocatechin-3-gallate (EGCG),
(-)-epigallocatechin (EGC), and (-)-epicatechin-3-gallate (ECG) from
green tea and theaflavins from black tea inhibited LOX-dependent
activity by 30-75%. The formation of 5-, 12-, and 15-LOX metabolites
was inhibited to a similar extent. Tea polyphenols also inhibited COX-
dependent arachidonic acid metabolism in microsomes from normal colon
mucosa, with ECG showing the strongest inhibition. The formation of
thromboxane (TBX) and 12-hydroxyheptadecatrienoic acid (HHT) was
decreased to a greater extent than other metabolites. The inhibitory
effects of tea polyphenols on COX activity, however, were less
pronounced in tumor microsomes than in normal colon mucosal
microsomes. Theaflavins strongly inhibited the formation of TBX and
HHT, but increased the production of prostaglandin E(2) (PGE(2)) in
tumor microsomes. The enhancing effect of theaflavins on PGE(2)
production was related to the COX-2 level in the microsomes. Although
theaflavin inhibited ovine COX-2, its activity in the formation of PGE
(2) was stimulated by theaflavin when ovine COX-2 was mixed with
microsomes, suggesting that theaflavin affects the interaction of
COX-2 with other microsomal factors (e.g. PGE synthase). The present
results indicate that tea polyphenols can affect arachidonic acid
metabolism in human colon mucosa and colon tumors, and this action may
alter the risk for colon cancer in humans.
PMID: 11705450
Int J Cancer. 2005 Feb 10;113(4):660-9.
Green tea constituent epigallocatechin-3-gallate selectively inhibits
COX-2 without affecting COX-1 expression in human prostate carcinoma
cells.
Hussain T, Gupta S, Adhami VM, Mukhtar H.
University of Wisconsin, Department of Dermatology, 1300 University
Ave., Madison, WI 53706, USA.
Overexpression of cyclooxygenase (COX)-2 has been implicated in many
pathologic conditions, including cancer. One practical inference of
this finding is that sustained inhibition of COX-2 could serve as a
promising target for prevention or therapy of cancer. Conventional
nonsteroidal antiinflammatory drugs (NSAIDs) and recently developed
COX-2-specific inhibitors have shown considerable promise in
prevention of some forms of human cancer; however, its application is
limited due to severe toxic side effects on normal cells. Therefore,
there is a need to define novel, nontoxic dietary constituents with
proven chemopreventive effects through other pathways that also
possess COX-2 but not COX-1 inhibitory activity. Recent studies on
green tea and its major polyphenolic constituent (-)epigallocatechin-3-
gallate (EGCG) have established its remarkable cancer preventive and
some cancer therapeutic effects. Here, we show that EGCG inhibits
COX-2 without affecting COX-1 expression at both the mRNA and protein
levels, in androgen-sensitive LNCaP and androgen-insensitive PC-3
human prostate carcinoma cells. Based on our study, it is tempting to
suggest that a combination of EGCG with chemotherapeutic drugs could
be an improved strategy for prevention and treatment of prostate
cancer.
PMID: 15455372
Anticancer Agents Med Chem. 2006 Sep;6(5):389-406.
Mechanisms of cancer prevention by green and black tea polyphenols.
Beltz LA, Bayer DK, Moss AL, Simet IM.
Department of Biology, University of Northern Iowa, Cedar Falls, IA
50614, USA.
Drinking green tea is associated with decreased frequency of cancer
development. This review outlines the wide range of mechanisms by
which epigallocatechin gallate (ECGC) and other green and black tea
polyphenols inhibit cancer cell survival. EGCG suppressed androgen
receptor expression and signalling via several growth factor
receptors. Cell cycle arrest or apoptosis involved caspase activation
and altered Bcl-2 family member expression. EGCG inhibited telomerase
activity and led to telomere fragmentation. While at high
concentrations polyphenols had pro-oxidative activities, at much lower
levels, anti-oxidative effects occurred. Nitric oxide production was
reduced by EGCG and black tea theaflavins by suppressing inducible
nitric oxide synthase via blocking nuclear translocation of the
transcription factor nuclear factor-kappaB as a result of decreased
IkappaB kinase activity. Polyphenols up- or down-regulated activity of
a number of key enzymes, including mitogen-activated protein kinases
and protein kinase C, and increased or decreased protein/mRNA levels,
including that of cyclins, oncogenes, and tumor suppressor genes.
Metastasis was inhibited via effects on urokinase and matrix
metalloproteinases. Polyphenols reduced angiogenesis, in part by
decreasing vascular endothelial growth factor production and receptor
phosphorylation. Recent work demonstrated that EGCG reduced
dihydrofolate reductase activity, which would affect nucleic acid and
protein synthesis. It also acted as an aryl hydrocarbon receptor an-
tagonist by directly binding the receptor's molecular chaperone, heat
shock protein 90. In conclusion, green and black tea polyphenols act
at numerous points regulating cancer cell growth, survival, and
metastasis, including effects at the DNA, RNA, and protein levels.
PMID: 17017850