From: healerstouch1 <healerstouch1@a...>
Date: Wed Apr 5, 2000 9:06pm
Subject: ELLAGIC ACID CLINICAL STUDIES
This first one is the most exciting news in medical history!
Cancer Lett 1999 Mar 1 1;136(2):215-21
Expression and its posssible role in G1 arrest and apoptosisi in ellagic
acid treated cancer cells.
Narayanan BA, Geoffroy O, Wilmington MC, Re GG, Nixon DWCANCER P
Prevention program, Hollings Cancer Center, Medical University of South
Carolina, Charleston 29425, USA.
Protective Effect of Curcumin, Ellagic Acid and Bixin on Radiation Induced
Genotoxicity
K.C. Thresiamma, J. George and R. Kuttan Amala Cancer Research Centre, Amala
Nagar, Trichur, India
Induction of micronuclei and chromosomal aberrations produced by whole body
exposure of r-radiation (1.5-3.0 Gy) in mice was found to be significantly
inhibited by oral administration of natural antioxidants, curcumin (400 µ
moles), ellagic acid (200 µ moles)
and bixin (200 µ moles) per kilogram body weight. These antioxidants induced
inhibition of micronucleated polychromatic and normochromatic erythrocytes,
was comparable with a-tocopherol (200 µ moles) administration. Curcumin and
ellagic acid were also found to significantly reduce the number of bone
marrow cells with chromosomal aberrations and chromosomal fragments as
effectively as a-tocopherol. Moreover, administration of antioxidants
inhibited the DNA strand breaks produced in rat lymphocytes upon radiation as
seen from the DNA unwinding studies. These results indicated that antioxidant
curcumin, ellagic acid and bixin provide protection against chromosome damage
produced by radiation.
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Inhibitory effects of ellagic acid on the direct-acting mutagenicity of
aflatoxin B1 in the Salmonella microsuspension assay.
Loarca-Pina G, Kuzmicky PA, de Mejia EG, Kado NY
Departamento de Investigacion y Posgrado, Facultad de Quimica, Universidad
Autonoma de Queretaro, Qro., Mexico. Ellagic acid (EA) is a phenolic compound
that exhibits both antimutagenic and anticarcinogenic activity in a wide
range of assays in vitro and in vivo. It occurs naturally in some foods such
as strawberries, raspberries, and grapes. In the previous work, we used the
Salmonella microsuspension assay to examine the antimutagenicity of EA
against the potent mutagen aflatoxin B1 (AFB1) using tester strains TA98 and
TA100. Briefly, the microsuspension assay was approximately 10 times more
sensitive than the standard Salmonella/microsome (Ames) test in detecting
AFB1 mutagenicity, and EA significantly inhibited mutagenicity of all AFB1
doses in both tester strains with the addition of S9. The greatest inhibitory
effect of EA on AFB1 mutagenicity occurred when EA and AFB1 were incubated
together (with metabolic enzymes). Lower inhibition was apparent when the
cells were first incubated with EA followed by a second incubation with AFB1,
or when the cells were first incubated with AFB1 followed by a second
incubation with EA alone, all with metabolic enzymes. The result of these
sequential incubation studies indicates that one mechanism of inhibition
could involve the formation of an AFB1-EA chemical complex. In the present
study, we further examine the effect of EA on AFB1 mutagenicity, but without
the addition of exogenous metabolic enzymes. We report the mutagenicity of
AFB1 in the microsuspension assay using TA98 and TA100 without the addition
of S9. Neither the concentrations of AFB1 (0.6, 1.2, and 2.4 microg/tube) nor
the concentrations of EA (0.3, 1.5, 3, 10, and 20 microg/tube) were toxic to
the bacteria. The results indicate that AFB1 is a direct-acting mutagen, and
that EA inhibits AFB1 direct-acting mutagenicity. PMID: 9626978
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Expression and its possible role in G1 arrest and apoptosis in ellagic acid
treated cancer cells.
Narayanan BA, Geoffroy O, Willingham MC, Re GG, Nixon DW
Cancer Prevention Program, Hollings Cancer Center, Medical University of
South Carolina, Charleston 29425, USA. bhagavati@m... Ellagic acid is a
phenolic compound present in fruits and nuts including raspberries,
strawberries and walnuts. It is known to inhibit certain carcinogen-induced
cancers and may have other chemopreventive properties. The effects of ellagic
acid on cell cycle events and apoptosis were studied in cervical carcinoma
(CaSki) cells. We found that ellagic acid at a concentration of 10(-5) M
induced G arrest within 48 h, inhibited overall cell growth and induced
apoptosis in CaSki cells after 72 h of treatment. Activation of the cdk
inhibitory protein p21 by ellagic acid suggests a role for ellagic acid in
cell cycle regulation of cancer cells. PMID: 10355751
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Regression of atherosclerosis: role of nitric oxide and apoptosis.
Wang BY, Ho HK, Lin PS, Schwarzacher SP, Pollman MJ, Gibbons GH, Tsao PS,
Cooke JP
Section of Vascular Medicine, Division of Cardiovascular Medicine, Stanford
University School of Medicine, Stanford, Calif, USA. <0.01). In subsequent
studies, aortas were harvested for ex vivo studies. Aortic segments were
incubated in cell culture medium for 4 to 24 hours with
modulators of the NO synthase pathway. The tissues were then collected for
histological studies and the conditioned medium collected for measurement of
nitrogen oxides by chemiluminescence. Addition of sodium nitroprusside
(10(-5) mol/L) to the medium caused a time-dependent increase in apoptosis of
vascular cells (largely macrophages) in the intimal lesion. L-Arginine
(10(-3) mol/L) had an identical effect on apoptosis, which was associated
with an increase in nitrogen oxides released into the medium. These effects
were not mimicked by D-arginine, and they were antagonized by the NO synthase
inhibitor L-nitro-arginine (10(-4) mol/L). The effect of L-arginine was not
influenced by an antagonist of cGMP-dependent protein kinase, nor was the
effect mimicked by the agonist of protein kinase G or 8-BR cGMP. CONCLUSIONS:
These results indicate that supplemental L-arginine induces apoptosis of
macrophages in intimal lesions by its metabolism to NO, which acts through a
GMP-independent pathway. These studies are consistent with our previous
observation that supplementation of dietary arginine induces regression of
atheroma in this animal model. These studies provide a rationale for further
investigation of the therapeutic potential of manipulating the NO synthase
pathway in atherosclerosis. PMID: 10069793
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Epidemic of gastroenteritis of viral origin associated with eating imported
raspberries.
Gaulin CD, Ramsay D, Cardinal P, D'Halevyn MA
Centre de sante publique de Quebec, Beauport. Several episodes of food
poisoning affected the region of Quebec City in July and August 1997. In the
first two episodes, the analysis of two cohorts (A and B) demonstrated that
the consumption of a raspberry mousse with raspberry sauce increased the risk
of contracting gastroenteritis (A, RR = 2.6 p = 0.001; B, RR = 4.7 p = 0.02).
More than 200 people were sick after eating a raspberry dessert. The common
ingredient of all those desserts was raspberries imported from Bosnia. Viral
studies on the raspberry sauce (2) and stool samples (5) using the genome
amplification method by PCR indicated the presence of genomic material
compatible with a virus of the Caliciviruses family. Southern hybridization
and sequence analysis showed that the nucleotide sequences found in the
raspberry sauce and in the stool samples were identical. It is important to
maintain active surveillance to detect and limit the spread of this kind of
outbreak. PMID: 10189738
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Protective effects of antioxidants on experimental liver injuries.
Suzuki M, Kumazawa N, Ohta S, Kamogawa A, Shinoda M
Faculty of Pharmaceutical Science, Hoshi University, Tokyo, Japan. Protective
effects of 14 kinds of antioxidant on liver injury induced by carbon
tetrachloride (CCl4) were investigated in terms of serum enzyme activities
and bilirubin concentration. Consequently, the significant protective effects
were found in sesamol, ellagic acid, cysteamine and cysteine. These
antioxidants clearly decreased the lipid peroxide in the liver tissue. The
protective effects on CCl4-induced liver injury in vivo were independent of
the inhibitory activities on lipid peroxidation in hepatic mitochondria
fraction in vitro. PMID: 2262882
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Polyphenols as cancer chemopreventive agents.
Stoner GD, Mukhtar H
Department of Preventive Medicine, Ohio State University, Columbus 43210,
USA. This article summarizes available data on the chemopreventive efficacies
of tea polyphenols, curcumin and ellagic acid in various model systems.
Emphasis is placed upon the anticarcinogenic activity of these polyphenols
and their proposed mechanism(s) of action. Tea is grown in about 30 countries
and, next to water, is the most widely consumed beverage in the world. Tea is
manufactured as either green, black, or oolong; black tea represents
approximately 80% of tea products. Epidemiological studies, though
inconclusive, suggest a protective effect of tea consumption on human cancer.
Experimental studies of the antimutagenic and anticarcinogenic effects of tea
have been conducted principally with green tea polyphenols (GTPs). GTPs
exhibit antimutagenic activity in vitro, and they inhibit carcinogen-induced
skin, lung, forestomach, esophagus, duodenum and colon tumors in rodents. In
addition, GTPs inhibit TPA-induced skin tumor promotion in mice. Although
several GTPs possess anticarcinogenic activity, the most active is
(-)-epigallocatechin-3-gallate (EGCG), the major constituent in the GTP
fraction. Several mechanisms appear to be responsible for the
tumor-inhibitory properties of GTPs, including enhancement of antioxidant
(glutathione peroxidase, catalase and quinone reductase) and phase II
(glutathione-S-transferase) enzyme activities; inhibition of chemically
induced lipid peroxidation; inhibition of irradiation- and TPA-induced
epidermal ornithine decarboxylase (ODC) and cyclooxygenase activities;
inhibition of protein kinase C and cellular proliferation;
antiinflammatory activity; and enhancement of gap junction intercellular
communication. Curcumin is the yellow coloring agent in the spice tumeric. It
exhibits antimutagenic activity in the Ames Salmonella test and has
anticarcinogenic activity, inhibiting chemically induced preneoplastic
lesions in the breast and colon and neoplastic lesions in the skin,
forestomach, duodenum and colon of rodents. In addition, curcumin inhibits
TPA-induced skin tumor promotion in mice. The mechanisms for the
anticarcinogenic effects of curcumin are similar to those of the GTPs.
Curcumin enhances glutathione content and glutathione-S-transferase activity
in liver; and it inhibits lipid peroxidation and arachidonic acid metabolism
in mouse skin, protein kinase C activity in TPA-treated NIH 3T3 cells,
chemically induced ODC and tyrosine protein kinase activities in rat colon,
and 8-hydroxyguanosine formation in mouse fibroblasts. Ellagic acid is a
polyphenol found abundantly in various fruits, nuts and vegetables. Ellagic
acid is active in antimutagenesis assays, and has been shown to inhibit
chemically induced cancer in the lung, liver, skin and esophagus of rodents,
and TPA-induced tumor promotion in mouse skin. PMID: 8538195
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Ellagic acid induces NAD(P)H:quinone reductase through activation of the
antioxidant responsive element of the rat NAD(P)H:quinone reductase gene.
Barch DH, Rundhaugen LM
Department of Medicine, Lakeside Veterans Affairs Medical Center, Chicago,
IL. Induction of cellular detoxification enzymes can increase detoxification
of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis.
To determine if the dietary anticarcinogen ellagic acid induced enzymes which
detoxify xenobiotics and carcinogens, we examined the effect of ellagic acid
on the expression of the phase II detoxification enzyme NAD(P)H:quinone
reductase (QR). QR is induced by xenobiotics and antioxidants interacting
with the xenobiotic responsive and antioxidant responsive elements of the 5'
regulatory region of the QR gene. Ellagic acid is structurally related to the
antioxidants which induce QR and we proposed that ellagic acid would induce
QR expression through activation of the antioxidant responsive element of the
QR gene. Rats fed ellagic acid demonstrated a 9-fold increase in hepatic and
a 2-fold increase in pulmonary QR activity, associated with an 8-fold
increase in hepatic QR mRNA. To determine if this increase in QR mRNA was due
to activation of the antioxidant responsive element, transient transfection
studies were performed with plasmid constructs containing various portions of
the 5' regulatory region of the rat QR gene. These transfection studies
confirmed that ellagic acid induces transcription of the QR gene and
demonstrated that this induction is mediated through the antioxidant
responsive element of the QR gene. PMID: 7522986
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Pulmonary carcinogenesis and its prevention by dietary polyphenolic compounds.
Castonguay A
Laboratory of Cancer Etiology and Chemoprevention, School of Pharmacy, Laval
University, Quebec City, Canada. The aims of this study were to define the
cumulative exposure of Canadian smokers to NNK and to characterize the
efficacy of ellagic acid to inhibit lung tumorigenesis induced by NNK. The
sales-weighted average of NNK deliveries from Canadian cigarettes was 73.2
ng/cigarette. NNK deliveries were highly correlated to declared tar values
and were linear with puff volumes between 20 and 50 ml. Ellagic acid
inhibited lung tumorigenesis induced by NNK in A/J mice. This inhibition was
related to the logarithm of the dose of ellagic acid added to the diet. The
biodistribution of ellagic acid was studied in mice gavaged with ellagic
acid. Pulmonary levels of ellagic acid were directly proportional to the dose
of ellagic acid between 0.2 and 2.0 mmol/kg b.w. PMID: 8512246
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Lung tumors in strain A mice: application for studies in cancer
chemoprevention.
Stoner GD, Adam-Rodwell G, Morse MA
Ohio State University, Department of Preventive Medicine, Arthur G. James
Cancer Hospital and Research Institute, Columbus 43210. Strain A mice develop
a high incidence of spontaneous lung tumors during their lifetime. These
tumors may be found in some animals as early as 3 to 4 weeks of age,
increasing to nearly 100% by 24 months of age. The strain A mouse is also
highly susceptible to the induction of lung tumors by several classes of
chemical carcinogens and has been used extensively as a mouse lung tumor
bioassay for assessing the carcinogenic activity of a variety of chemicals.
In addition to its use in carcinogen detection, the strain A mouse lung tumor
model has been employed extensively for the identification of inhibitors of
chemical carcinogenesis. A number of chemopreventive agents including
beta-naphthoflavone, butylated hydroxyanisole, ellagic acid, phenethyl
isothiocyanate, phenylpropyl isothiocyanate, phenylbutyl isothiocyanate,
phenylhexyl isothiocyanate, indole-3-carbinol, etc., have been shown to
inhibit chemically induced lung tumors in strain A mice. In most instances,
inhibition of lung tumorigenesis has been correlated with effects of the
chemopreventive agent on the metabolic activation and/or detoxification of
carcinogens. To date, no chemopreventive agent has been shown to inhibit lung
tumorigenesis in strain A mice when administered after the carcinogen, i.e.,
during the promotion/progression stages of tumor development. Efforts should
be made to develop a standardized protocol in strain A mice for evaluating
chemopreventive agents as inhibitors of both the initiation and progression
stages of lung tumor development. PMID: 8412213
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Medical research confirms eating red raspberries may be one of the most
potent ways to fight cancer.
Dr. Daniel Nixon, Medical University of South Carolina
(JANUARY-1999) -- One of the most popular and flavorful fruits on the market
now has an entirely new reason for becoming a part of a healthy diet. Recent
medical tests have shown that the red raspberry is one of the most effective
all-natural ways to fight certain forms of cancer.
Red raspberries have the highest content of ellagic acid, a phenolic compound
that is a proven anti-carcinogen, anti-mutagen and anti-cancer initiator.
Tests conducted at the Hollings Cancer Center at the Medical University of
South Carolina have revealed that the ellagic acid from red raspberries is
readily absorbed by the human body. This ellagic acid has been clinically
shown to cause apoptosis (cell death) in cancer cells.
Additional tests have revealed that the ellagic acid in red raspberries
retains its potency after heating, freezing and concentration processing. So
whether consumed fresh, in juices, fruit spreads, preserves or sorbets, the
red raspberry should become a part of any healthy diet.