Free Radic Res 2002 Sep;36(9):1023-31
Anti-angiogenic property of edible berries.
Roy S, Khanna S, Alessio HM, Vider J, Bagchi D, Bagchi M, Sen CK.
Laboratory of Molecular Medicine, Department of Surgery, 512 Heart and Lung
Research Institute, Ohio State University Medical Center, 473 W. 12th Avenue,
Columbus, OH 43210, USA.
Recent studies show that edible berries may have potent chemopreventive
properties. Anti-angiogenic approaches to prevent and treat cancer represent a
priority area in investigative tumor biology. Vascular endothelial growth factor
(VEGF) plays a crucial role for the vascularization of tumors. The vasculature
in adult skin remains normally quiescent. However, skin retains the capacity for
brisk initiation of angiogenesis during inflammatory skin diseases such as
psoriasis and skin cancers. We sought to test the effects of multiple berry
extracts on inducible VEGF expression by human HaCaT keratinocytes. Six berry
extracts (wild blueberry, bilberry, cranberry, elderberry, raspberry seed, and
strawberry) and a grape seed proanthocyanidin extract (GSPE) were studied. The
extracts and uptake of their constituents by HaCaT were studied using a
multi-channel HPLC-CoulArray approach. Antioxidant activity of the extracts was
determined by ORAC. Cranberry, elderberry and raspberry seed samples were
observed to possess comparable ORAC values. The antioxidant capacity of these
samples was significantly lower than that of the other samples studied. The ORAC
values of strawberry powder and GSPE were higher than cranberry, elderberry or
raspberry seed but significantly lower than the other samples studied. Wild
bilberry and blueberry extracts possessed the highest ORAC values. Each of the
berry samples studied significantly inhibited both H2O2 as well as TNF alpha
induced VEGF expression by the human keratinocytes. This effect was not shared
by other antioxidants such as alpha-tocopherol or GSPE but was commonly shared
by pure flavonoids. Matrigel assay using human dermal microvascular endothelial
cells showed that edible berries impair angiogenesis.
Mutat Res 2001 Sep 1;480-481:97-108
Effect of chemopreventive agents on DNA adduction induced by the potent mammary
carcinogen dibenzo[a,l]pyrene in the human breast cells MCF-7.
Smith WA, Freeman JW, Gupta RC.
Graduate Center for Toxicology, 354 Health Sciences Research Building,
University of Kentucky Medical Center, Lexington, KY 40536-0305, USA.
Over 1500 structurally diverse chemicals have been identified which have
potential cancer chemopreventive properties. The efficacy and mechanisms of this
growing list of chemoprotective agents may be studied using short-term bioassays
that employ relevant end-points of the carcinogenic process. In this study, we
have examined the effects of eight potential chemopreventive agents, N-acetylcysteine
(NAC), benzylisocyanate (BIC), chlorophyllin, curcumin, 1,2-dithiole-3-thione
(D3T), ellagic acid, genistein, and oltipraz, on DNA adduction of the potent
mammary carcinogen dibenzo[a,l]pyrene (DBP) using the human breast cell line
MCF-7. Bioactivation of DBP by MCF-7 cells resulted in the formation of one
predominant (55%) dA-derived and several other dA- or dG-derived DNA adducts.
Three test agents, oltipraz, D3T, and chlorophyllin substantially (>65%)
inhibited DBP-DNA adduction at the highest dose tested (30 microM). These agents
also significantly inhibited DBP adduct levels at a lower dose of 15 microM,
while oltipraz was effective even at the lowest dose of 5 microM. Two other
agents, genistein and ellagic acid were moderate (45%) DBP-DNA adduct inhibitors
at the highest dose tested, while NAC, curcumin, and BIC were ineffective. These
studies indicate that the MCF-7 cell line is an applicable model to study the
efficacy of cancer chemopreventive agents in a human setting. Moreover, this
model may also provide information regarding the effect of the test agents on
carcinogen bioactivation and detoxification enzymes.
Eur J Drug Metab Pharmacokinet 1999 Apr-Jun;24(2):183-9
Tannins, xenobiotic metabolism and cancer chemoprevention in experimental
animals.
Nepka C, Asprodini E, Kouretas D.
Cytopathology Laboratory, Serres, Greece.
Tannins are plant polyphenolic compounds that are contained in large quantities
in food and beverages (tea, red wine, nuts, etc.) consumed by humans daily. It
has been shown that various tannins exert broad cancer chemoprotective activity
in a number of animal models. This review summarizes the recent literature
regarding both the mechanisms involved, and the specific organ cancer models
used in laboratory animals. An increasing body of evidence demonstrates that
tannins act as both anti-initiating and antipromoting agents. In view of the
fact that tannins may be of valid medicinal efficacy in human clinical trials,
the present review attempts to integrate results from animal studies, and
considers their possible application in humans.
Carcinogenesis 1996 Apr;17(4):821-8
The effects of dietary ellagic acid on rat hepatic and esophageal mucosal
cytochromes P450 and phase II enzymes.
Ahn D, Putt D, Kresty L, Stoner GD, Fromm D, Hollenberg PF.
Department of Surgery, Wayne State University, Detroit, MI 48201, USA.
Ellagic acid (EA), a naturally occurring plant polyphenol possesses broad
chemoprotective properties. Dietary EA has been shown to reduce the incidence of
N-2-fluorenylacetamide-induced hepatocarcinogenesis in rats and N-nitrosomethylbenzylamine
(NMBA)-induced rat esophageal tumors. In this study changes in the expression
and activities of specific rat hepatic and esophageal mucosal cytochromes P450
(P450) and phase II enzymes following dietary EA treatment were investigated.
Liver and esophageal mucosal microsomes and cytosol were prepared from three
groups of Fisher 344 rats which were fed an AIN-76 diet containing no EA or 0.4
or 4.0 g/kg EA for 23 days. In the liver total P450 content decreased by up to
25% and P450 2E1-catalyzed p-nitrophenol hydroxylation decreased by 15%. No
changes were observed in P450 1A1, 2B1 or 3A1/2 expression or activities or
cytochrome b5 activity. P450 reductase activity decreased by up to 28%.
Microsomal epoxide hydrolase (mEH) expression decreased by up to 85% after EA
treatment, but mEH activities did not change. The hepatic phase II enzymes
glutathione S-transferase (GST), NAD(P)H:quinone reductase ?NAD-(P)H:QR? and UDP
glucuronosyltransferase (UDPGT) activities increased by up to 26, 17 and 75%
respectively. Assays for specific forms of GST indicated marked increases in the
activities of isozymes 2-2 (190%), 4-4 (150%) and 5-5 (82%). In the rat
esophageal mucosa only P450 1A1 could be detected by Western blot analysis and
androstendione was the only P450 metabolite of testosterone detectable. However,
there were no differences in the expression of P450 1A1, the formation of
androstendione or NAD(P)H:QR activities between control and EA-fed rats in the
esophagus. Although there was no significant decrease in overall GST activity,
as measured with 1-chloro-2,4-dinitrobenzene (CDNB), there was a significant
decrease in the activity of the 2-2 isozyme (66% of control). In vitro
incubations showed that EA at a concentration of 100 microM inhibited P450 2E1,
1A1 and 2B1 activities by 87, 55 and 18% respectively, but did not affect 3A1/2
activity. Using standard steady-state kinetic analyses, EA was shown to be a
potent non-competitive inhibitor of both liver microsomal ethoxyresorufin O-deethylase
and p-nitrophenol hydroxylase activities, with apparent Ki values of
approximately 55 and 14 microM respectively. In conclusion, these results
demonstrate that EA causes a decrease in total hepatic P450 with a significant
effect on hepatic P450 2E1, increases some hepatic phase II enzyme activities ?GST,
NAD-(P)H:QR and UDPGT? and decreases hepatic mEH expression. It also inhibits
the catalytic activity of some P450 isozymes in vitro. Thus the chemoprotective
effect of EA against various chemically induced cancers may involve decreases in
the rates of metabolism of these carcinogens by phase I enzymes, due to both
direct inhibition of catalytic activity and modulation of gene expression, in
addition to effects on the expression of phase II enzymes, thereby enhancing the
ability of the target tissues to detoxify the reactive intermediates
Cancer Lett 1999 Mar 1;136(2):215-21
p53/p21(WAF1/CIP1) 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@musc.edu
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.
Cancer Res 2001 Aug 15;61(16):6112-9
Chemoprevention of esophageal tumorigenesis by dietary administration of
lyophilized black raspberries.
Kresty LA, Morse MA, Morgan C, Carlton PS, Lu J, Gupta A, Blackwood M, Stoner GD.
Division of Environmental Health Sciences, School of Public Health,
Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210,
USA.
Fruit and vegetable consumption has consistently been associated with decreased
risk of a number of aerodigestive tract cancers, including esophageal cancer. We
have taken a "food-based" chemopreventive approach to evaluate the inhibitory
potential of lyophilized black raspberries (LBRs) against N-nitrosomethylbenzylamine
(NMBA)-induced esophageal tumorigenesis in the F344 rat, during initiation and
postinitiation phases of carcinogenesis. Anti-initiation studies included a
30-week tumorigenicity bioassay, quantification of DNA adducts, and NMBA
metabolism study. Feeding 5 and 10% LBRs, for 2 weeks prior to NMBA treatment
(0.25 mg/kg, weekly for 15 weeks) and throughout a 30-week bioassay,
significantly reduced tumor multiplicity (39 and 49%, respectively). In a
short-term bioassay, 5 and 10% LBRs inhibited formation of the promutagenic
adduct O(6)-methylguanine (O(6)-meGua) by 73 and 80%, respectively, after a
single dose of NMBA at 0.25 mg/kg. Feeding 5% LBRs also significantly inhibited
adduct formation (64%) after NMBA administration at 0.50 mg/kg. The
postinitiation inhibitory potential of berries was evaluated in a second
bioassay with sacrifices at 15, 25, and 35 weeks. Administration of LBRs began
after NMBA treatment (0.25 mg/kg, three times per week for 5 weeks). LBRs
inhibited tumor progression as evidenced by significant reductions in the
formation of preneoplastic esophageal lesions, decreased tumor incidence and
multiplicity, and reduced cellular proliferation. At 25 weeks, both 5 and 10%
LBRs significantly reduced tumor incidence (54 and 46%, respectively), tumor
multiplicity (62 and 43%, respectively), proliferation rates, and preneoplastic
lesion development. Yet, at 35 weeks, only 5% LBRs significantly reduced tumor
incidence and multiplicity, proliferation indices and preneoplastic lesion
formation. In conclusion, dietary administration of LBRs inhibited events
associated with both the initiation and promotion/progression stages of
carcinogenesis, which is promising considering the limited number of
chemopreventives with this potential.
Cancer Res 2001 Aug 15;61(16):6112-9
Bioorg Med Chem Lett 1998 Jan 6;8(1):97-100
DNA gyrase inhibitory activity of ellagic acid derivatives.
Weinder-Wells MA, Altom J, Fernandez J, Fraga-Spano SA, Hilliard J, Ohemeng K,
Barrett JF.
R.W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869, USA.
Ellagic acid was found to inhibit E. coli DNA gyrase supercoiling with
approximately the same potency as nalidixic acid. Tricyclic analogs of ellagic
acid, which vary in the number and position of the hydroxy groups as well as
their replacement with halogens, have been synthesized. The biological activity
of these analogs is discussed
Eksp Klin Farmakol 2001 Mar-Apr;64(2):55-9
[Antioxidant properties of novel preparations--bioflavonoid derivatives and
tannins.]
[Article in Russian]
Iakovleva LV, Gerasimova OA, Karbusheva IV, Ivakhnenko AK, Buniatian ND,
Sakharova TS.
Central Research Laboratory, Ukrainian Pharmaceutical Academy, ul. Pushkinskaya
53, Kharkov, 310002 Ukraine.
New medicinal plant preparations of polyphenol nature, representing the
derivatives of bioflavonoids (piflamin) and ellagotannins (altan and ellagic
acid) were experimentally studied. The drugs exhibited antioxidant properties,
which were manifested by inhibition of a pathological lipid peroxidation,
restoration of the functional activity of the antioxidant system components, and
stabilization of the hepatocyte membranes.
Antimicrob Agents Chemother 1998 Sep;42(9):2245-53
Human immunodeficiency virus type 1 cDNA integration: new aromatic hydroxylated
inhibitors and studies of the inhibition mechanism.
Farnet CM, Wang B, Hansen M, Lipford JR, Zalkow L, Robinson WE Jr, Siegel J,
Bushman F.
Salk Institute for Biological Studies, La Jolla, California, USA.
Integration of the human immunodeficiency virus type 1 (HIV-1) cDNA is a
required step for viral replication. Integrase, the virus-encoded enzyme
important for integration, has not yet been exploited as a target for clinically
useful inhibitors. Here we report on the identification of new polyhydroxylated
aromatic inhibitors of integrase including ellagic acid, purpurogallin, 4,8,
12-trioxatricornan, and hypericin, the last of which is known to inhibit viral
replication. These compounds and others were characterized in assays with
subviral preintegration complexes (PICs) isolated from HIV-1-infected cells.
Hypericin was found to inhibit PIC assays, while the other compounds tested were
inactive. Counterscreening of these and other integrase inhibitors against
additional DNA-modifying enzymes revealed that none of the polyhydroxylated
aromatic compounds are active against enzymes that do not require metals (methylases,
a pox virus topoisomerase). However, all were cross-reactive with
metal-requiring enzymes (restriction enzymes, a reverse transcriptase),
implicating metal atoms in the inhibitory mechanism. In mechanistic studies, we
localized binding of some inhibitors to the catalytic domain of integrase by
assaying competition of binding by labeled nucleotides. These findings help
elucidate the mechanism of action of the polyhydroxylated aromatic inhibitors
and provide practical guidance for further inhibitor development.
Microbios 1998;93(375):115-27
Inhibitory actions of ellagic acid on growth and arylamine N-acetyltransferase
activity in strains of Helicobacter pylori from peptic ulcer patients.
Chung JG.
Department of Medicine, China Medical College, Taiwan, Republic of China.
Arylamine N-acetyltransferase (NAT) activity in Helicobacter pylori was
inhibited by ellagic acid, a possible chemopreventive drug. The NAT activity was
determined using an acetyl CoA recycling assay and high pressure liquid
chromatography. Inhibition of growth studies using H. pylori demonstrated that
ellagic acid elicited a dose-dependent bactericidal effect in H. pylori
cultures, i.e. the greater the concentration of ellagic acid, the greater the
inhibition of growth of H. pylori. The IC50 value was 1 mM for inhibition of
growth of H. pylori. Cytosols or suspensions of H. pylori with and without
selected concentrations of ellagic acid co-treatment showed different
percentages of 2-aminofluorene and p-aminobenzoic acid acetylation. The data
indicated that there was decreased NAT activity associated with increased
ellagic acid in H. pylori cytosols and intact cells. For the cytosol and intact
bacteria examinations, the apparent values of K(m) and Vmax decreased after
co-treatment with 1 mM ellagic acid. This report is the first demonstration of
ellagic acid inhibition of arylamine NAT activity and ellagic acid inhibition of
growth in the bacterium H. pylori.
Indian J Physiol Pharmacol 1996 Oct;40(4):363-6
Inhibition of liver fibrosis by ellagic acid.
Thresiamma KC, Kuttan R.
Amala Cancer Research Centre, Amala Nagar, Trichur, Kerala.
Chronic administration of carbon tetrachloride in liquid paraffin (1.7) ip; 0.15
ml, (20 doses) has been found to produce severe hepatotoxicity, as seen from the
elevated levels of serum and liver glutamate-pyruvate transaminase, alkaline
phosphatase and lipid peroxides. The chronic administration of carbon
tetrachloride was also found to produce liver fibrosis as seen from pathological
analysis as well as elevated liver-hydroxy proline. Oral administration of
ellagic acid was found to significantly reduce the elevated levels of enzymes,
lipid peroxide and liver hydroxy proline in these animals and rectified liver
pathology. These results indicate that ellagic acid administration orally can
circumvent the carbon tetrachloride toxicity and subsequent fibrosis
Eksp Klin Farmakol 1998 May-Jun;61(3):32-4
[The protective action of ellagic acid in experimental myocarditis]
[Article in Russian]
Iakovleva LV, Ivakhnenko AK, Buniatian ND.
Central Research Laboratory, Ukranian Pharmaceutical Academy, Kharkov, Ukraine.
The article presents the material on the study of the cardioprotective effect of
ellagic acid on a model of neoepinephrine myocarditis in rats. In doses of 0.5-1
mg/kg ellagic acid causes a marked antioxidant effect. Restores the disturbed
myocardial functions. The reference-agent vitamin E (50 mg/kg) yields to ellagic
acid as a cardioprotector. The effect of 0.5 mg/kg of ellagic acid was more
stable than that of a 1 mg/kg dose. The cardioprotective activity of the drugs
under study was determined according to the POL parameters in a myocardial
homogenate and blood serum and according to the EEG parameters and the degree of
cardiomyocyte cytolysis.
J Nat Prod 2001 Aug;64(8):1010-4
Ellagitannins and hexahydroxydiphenoyl esters as inhibitors of vertebrate
squalene epoxidase.
Abe I, Kashiwagi Y, Noguchi H, Tanaka T, Ikeshiro Y, Kashiwada Y.
School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526,
Japan. abei@ys7.u-shizuoka-ken.ac.jp
Ellagitannins isolated from various plant sources as well as newly synthesized
n-alkyl (C(1)-C(18)) esters of hexahydroxydiphenyl (HHDP) dicarboxylic acid were
evaluated as enzyme inhibitors of recombinant rat squalene epoxidase, a
rate-limiting enzyme of cholesterol biosynthesis. Among the ellagitannins
tested, pedunculagin (IC(50) = 2.0 microM) and eugeniin (IC(50) = 1.6 microM),
both containing (S)-HHDP ester group(s), showed remarkable inhibition, which was
more potent than those of previously reported substrate analogue inhibitors.
Furthermore, ellagic acid (IC(50) = 2.0 microM), a bislactone formed by
hydrolytic release of a HHDP group from ellagitannins, was also a good inhibitor
of the enzyme. On the other hand, the synthetic HHDP esters with C(6) (IC(50) =
0.93 microM) and C(8) alkyl side chains (IC(50) = 0.83 microM) showed potent
enzyme inhibition at the submicromolar concentration range, while esters with
shorter chain lengths (C(1)-C(4)) and a C(18) ester exhibited moderate
inhibition (IC(50) = 8-47 microM).
Planta Med 2001 Dec;67(9):825-32
Antileishmanial activity of hydrolyzable tannins and their modulatory effects on
nitric oxide and tumour necrosis factor-alpha release in macrophages in vitro.
Kolodziej H, Kayser O, Kiderlen AF, Ito H, Hatano T, Yoshida T, Foo LY.
Institut fur Pharmazie, Pharmazeutische Biologie, Freie Universitat Berlin,
Berlin, Germany. kolpharm@zedat-fu-berlin.de
A series of 27 hydrolyzable tannins and related compounds was tested for
antiparasitic effects against both extracellular promastigote and intracellular
amastigote Leishmania donovani organisms. In parallel, the compounds were
evaluated for their immunomodulatory effects on macrophage functions, including
release of nitric oxide (NO), tumour necrosis factor-alpha (TNF-alpha) and
interferon (IFN)-like properties using several functional assays. Of the series
of polyphenols tested, only gallic acid (54 microM NO) and its methyl ester (32
microM NO) induced murine macrophage-like RAW 264.7 cells to release NO in
appreciable amounts (IFN-gamma/LPS 119 microM NO). The in vitro TNF-inducing
potential of the polyphenols examined increased in the order of oligomeric
ellagitannins (EC(50) > 25 microg/ml) < monomeric ellagitannins, gallotannins
(EC(50) 8.5 to > 25 microg/ml) < C-glucosidic ellagitannins,
dehydroellagitannins (EC(50) 0.6 - 2.8 microg/ml) at the host cell subtoxic
concentration of 50 microg/ml. Furthermore, promastigotes of Leishmania donovani
were assayed in the presence of these polyphenols and the results showed that
none of the compounds was significantly toxic (EC(50) > 25 microg/ml) to the
extracellular forms. In contrast, all polyphenols showed pronounced
antileishmanial activities (EC(50) < 0.4 - 12.5 versus 7.9 microg/ml for
Pentostam) against intracellular amastigotes of L. donovani residing within RAW
cells. Noteworthy, most compounds exhibited low cytotoxicity against the murine
host cells (EC(50) >25 microg/ml). Furthermore, some ellagitannins and the
majority of dehydroellagitannins induced potent interferon-like activities as
reflected by inhibition of the cytopathic effect of encephalomyocarditis virus
on fibroblast L929 cells. This is the first report on hydrolyzable tannins as a
new class of natural products with leishmanicidal activity including their
potential for inducing the release of NO, TNF and IFN-like activity in
macrophage-like RAW cells.
Antioxid Redox Signal 2001 Dec;3(6):995-1008
Chemical studies of proanthocyanidins and hydrolyzable tannins.
Bors W, Foo LY, Hertkorn N, Michel C, Stettmaier K.
Institut fur Strahlenbiologie, GSF Forschungszentrum fur Umwelt und Gesundheit,
Neuherberg, Germany. bors@gsf.de
We investigated a number of natural polyphenols representing flavan-3-ols,
gallotannins, and ellagitannins with regard to their antioxidant potential. For
this purpose we used pulse radiolysis to determine scavenging rate constants
with hydroxyl radicals and decay rates of the respective aroxyl radicals and EPR
spectroscopy to identify the radicals after in situ oxidation. Using NMR
spectroscopy, we could confirm phenolic coupling reactions of epigallocatechin
gallate and pentagalloyl glucose after radical-induced oxidation.
Planta Med 2002 Feb;68(2):173-5
Ellagitannins from Lagerstroemia speciosa as Activators of Glucose Transport in
Fat Cells.
Hayashi T, Maruyama H, Kasai R, Hattori K, Takasuga S, Hazeki O, Yamasaki K,
Tanaka T.
Institute of Pharmaceutical Sciences, Faculty of Medicine, Hiroshima University,
Hiroshima, Japan.
Abstract.Glucose transport enhancers were searched for in Lagerstroemia speciosa,
a Philippine local herbal medicine used for diabetes mellitus. Bioassay-guided
fractionation of the aqueous acetone extract of the leaves afforded three active
ellagitannins, lagerstroemin, flosin B and reginin A, identified by NMR and
optical rotation. These compounds increased glucose uptake of rat adipocytes,
and could be responsible for lowering the blood glucose level.
Nutr 2001 Nov;131(11):2837-42
Walnut polyphenolics inhibit in vitro human plasma and LDL oxidation.
Anderson KJ, Teuber SS, Gobeille A, Cremin P, Waterhouse AL, Steinberg FM.
Department of Internal Medicine, Division of Rheumatology, Allergy and Clinical
Immunology, School of Medicine, University of California, Davis, CA, USA.
Recent epidemiologic studies have associated nut consumption with a reduced
incidence of cardiovascular mortality. However, little is known about the
contribution of nut polyphenols to antioxidant and cardiovascular protection. In
this investigation, polyphenol-rich extracts from English walnuts (Juglans regia)
were studied and compared with ellagic acid for their ability to inhibit in
vitro plasma and LDL oxidation, as well as their effects on LDL alpha-tocopherol
during oxidative stress. In addition, the Trolox equivalent antioxidant activity
(TEAC) was determined and liquid chromatography electrospray detection mass
spectrometry (LC-ELSD/MS) analyses of the walnut extracts were performed.
2,2'-Azobis'(2-amidino propane) hydrochloride (AAPH)-induced LDL oxidation was
significantly inhibited by 87 and 38% with the highest concentration (1.0
micromol/L) of ellagic acid and walnut extract, respectively. In addition,
copper-mediated LDL oxidation was inhibited by 14 and 84% in the presence of
ellagic acid and walnut extract, respectively, with a modest, significant LDL
alpha-tocopherol sparing effect observed. Plasma thiobarbituric acid reacting
substance (TBARS) formation was significantly inhibited by walnut extracts and
ellagic acid in a dose-dependent manner, and the extracts exhibited a TEAC value
greater than that of alpha-tocopherol. LC-ELSD/MS analysis of the walnut
extracts identified ellagic acid monomers, polymeric ellagitannins and other
phenolics, principally nonflavonoid compounds. These results demonstrate that
walnut polyphenolics are effective inhibitors of in vitro plasma and LDL
oxidation. The polyphenolic content of walnuts should be considered when
evaluating their antiatherogenic potential.
Anticancer Res 2001 Jan-Feb;21(1A):359-64
IGF-II down regulation associated cell cycle arrest in colon cancer cells
exposed to phenolic antioxidant ellagic acid.
Narayanan BA, Re GG.
American Health Foundation, 1, Dana Road Valhalla, NY 10595, USA. bhagavat@earthlink.net
Altered cell and tissue differentiation is characteristic of premalignant
lesions long before they become invasive and metastatic. One approach to
controlling preneoplastic lesions is to block their expansion with non-toxic
agents that suppress cell proliferation and induce apoptosis. Here, we show that
ellagic acid, a natural, dietary phenolic antioxidant when given at 10(-5) M for
48 hours to colon cancer cells (SW 480), induced down regulation of insulin like
growth factor IGF-II, activated p21(waf1/Cip1), mediated a cumulative effect on
G1/S transition phase and caused apoptotic cell death. SW480 colon cancer cells
expressed significant mRNA levels for the mitogenic insulin like growth factor (IGF-II).
Collectively, these observations suggest that growth inhibition by ellagic acid
is mediated by signaling pathways that mediate DNA damage, triggers p53, which
in turn activates p21 and at the same time alters the growth factor expression,
resulting in the down regulation of IGF-II.
Cancer Lett 1997 Mar 19;114(1-2):11-7 Related Articles, Books, LinkOut
Experimental evidence for cancer preventive elements in foods.
Wargovich MJ.
Department of Gastrointestinal Medical Oncology and Digestive Diseases, The
University of Texas M.D. Anderson Cancer Center, Houston, USA.
The last decade has witnessed an incredible advance in our understanding of how
fruits and vegetables work to prevent cancer. Epidemiological studies have
suggested that a diet rich in fruits and vegetables is associated with reduced
risk for a number of common cancers. Food chemists and natural product
scientists have identified hundreds of 'phytochemicals' that are being evaluated
for the prevention of cancer. Food components can modify carcinogenesis in one
of five different ways. They may: (1) modify carcinogen activation by inhibiting
Phase 1 enzymes; (2) modify how carcinogens are detoxified through Phase 2
pathways; (3) scavenge DNA reactive agents; (4) suppress the abnormal
proliferation of early, preneoplastic lesions; and (5) inhibit certain
properties of the cancer cell.