Resveratrol
1:
Int J Tissue React 1999;21(4):93-104 |
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Resveratrol, a natural
stilbene in grapes and wine, enhances intraphagocytosis
in human promonocytes: a co-factor in antiinflammatory
and anticancer chemopreventive activity.
Bertelli AA, Ferrara F, Diana G, Fulgenzi A, Corsi
M, Ponti W, Ferrero ME, Bertelli A
Institute of Human Anatomy, Faculty of Medicine, University
of Milan, Italy. MariaElena.Ferrero@unimi.it
Trans-resveratrol, a natural stilbene present in wine
and grapes, has been studied mainly for its antiinflammatory
and anticancer activities. In this study the activity
of resveratrol on proliferative immunological parameters
(differentiation, apoptosis, phagocytosis and intracellular
killing) was studied using a U937 human promonocytic
cell line in comparison with another polyphenol, quercetin.
After incubation of the pathogen, Candida albicans,
intracellular killing by macrophage-like cells was decreased
by quercetin and resveratrol 10 microM but was enhanced
by resveratrol 1 microM after 20 h of treatment. Phagocytosis
rate, expressed as phagocytosis frequency, (i.e., percentage
number of phagocytosing cells/total cells) at 20 h was
highest with resveratrol 10 microM and was higher with
quercetin 10 microM than with resveratrol 1 microM.
The phagocytosis index exhibited the same trend. While
both polyphenols demonstrated cytostatic activity on
U937 growth, a prointraphagocytic effect for resveratrol
10 microM-treated cells at 10 min, resveratrol 1 microM-treated
cells at 20 h and resveratrol 10 microM-treated cells
at 48 h was observed. Morphological examination with
optic microscopy demonstrated both apoptotic and differentiating
cells, even after 10 min treatment. Resveratrol-induced
apoptosis (following 4 h treatment) was confirmed by
flow cytometry at concentrations as low as 1 microM
and 100 nM in the assay for detection of membrane phosphatidylserine.
Resveratrol- or quercetin-treated, but unstimulated
cells, did not produce tumor necrosis factor-alpha protein.
As phosphatidylserine externalization triggers specific
recognition by monocytes and macrophages, removal of
intact apoptotic cells is important a) in cell population
selection and differentiation for antiblastic therapy,
and b) in preventing the release of toxic inflammatory
substances such as reactive oxygen substances and proteolytic
enzymes by dying cells. This observation suggests that
wine polyphenols, at the same concentrations as those
found in plasma after moderate wine consumption, are
important cofactors in antiinfective, antiinflammatory
and anticancer nonspecific immune reactions.
PMID: 10761539, UI: 20224605
1:
Biochem Biophys Res Commun 2000 Sep
7;275(3):804-809 |
|
Resveratrol Reverses
Tumor-Promoter-Induced Inhibition of Gap-Junctional
Intercellular Communication.
Nielsen M, Ruch RJ, Vang O
Department of Chemistry and Life Sciences, Roskilde
University, Roskilde, DK-4000, Denmark
[Record supplied by publisher]
The naturally occurring stilbene/alexin trans-resveratrol
(trans-3,5,4'-trihydroxystilbene) is a promising agent
for the prevention of cancer. We investigated the effect
of resveratrol on gap-junctional intercellular communication
(GJIC) in WB-F344 rat liver epithelial cells because
inhibition of GJIC is an important mechanism of tumor
promotion. Seventeen to 50 muM resveratrol increased
GJIC significantly by a factor of 1.3 compared with
solvent vehicle controls, when the WB-F344 cells were
exposed to resveratrol for 6 h. Most tumor promoters,
including the phorbol ester TPA and the insecticide
DDT, block GJIC. Resveratrol at 17-50 muM also significantly
prevented down-regulation of GJIC by TPA and DDT, by
a factor of 2.7 and 1.8, respectively. This recovery
of GJIC from TPA inhibition was partly correlated with
hindered hyperphosphorylation of Cx43. In conclusion,
resveratrol was found to enhance GJIC and counteract
the effects of tumor promoters on GJIC, and this is
likely a mechanism that contributes to the antipromotional
and anticarcinogenic properties of resveratrol. Copyright
2000 Academic Press.
PMID: 10973802
1:
Cardiovasc Res 2000 Aug 18;47(3):549-55 |
|
Cardioprotective effect
of resveratrol, a natural antioxidant derived from grapes.
Hung L, Chen J, Huang S, Lee R, Su M
Institute of Pharmacology, College of Medicine, National
Taiwan University, No. 1, Sec. 1, Jen-Ai Road, Taipei,
Taiwan.
[Medline record in process]
Background: The major objective of the present study
was to examine the cardioprotective effect of resveratrol,
an antioxidant presents in red wines, in the rat after
ischemia and ischemia-reperfusion (I-R). Methods: The
left main coronary artery was occluded for 30 or 5 min
followed by a 30-min reperfusion in anesthetized rats.
Animals were preinfused with and without resveratrol
before occlusion and the severity of ischemia- and I-R-induced
arrhythmias and mortality were compared. Results: Resveratrol
pretreatment had no effect on ischemia-induced arrhythmias
nor on mortality. In contrast, a dramatic protective
effects were observed against I-R-induced arrhythmias
and mortality. Resveratrol pretreatment both reduced
the incidence and duration of ventricular tachycardia
(VT) and ventricular fibrillation (VF). During the same
period, resveratrol pretreatment also increased nitric
oxide (NO) and decreased lactate dehydrogenase levels
in the carotid blood. Conclusions: Resveratrol is a
potent antiarrhythmic agent with cardioprotective properties
in I-R rats. The cardioprotective effects of resveratrol
in the I-R rats may be correlated with its antioxidant
activity and upregulation of NO production.
PMID: 10963727, UI: 20419793
1:
Cancer Lett 2000 Sep 29;158(1):85-91 |
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Anti-proliferative effect
of resveratrol, a natural component of grapes and wine,
on human colonic cancer cells.
Schneider Y, Vincent F, Duranton B, Badolo L, Gosse
F, Bergmann C, Seiler N, Raul F
ULP/CJF INSERM 95-09, Laboratory of Metabolic and Nutritional
Control in Digestive Oncology, IRCAD, 1 Place de l'Hopital,
67091, Strasbourg, France
[Record supplied by publisher]
Resveratrol, a natural polyphenolic phytoalexine present
in grapes and wines, has been reported to exert a variety
of important pharmacological effects. We investigated
the effects of resveratrol on the growth and polyamine
metabolism of CaCo-2 human colon cancer cells. Treatment
of the CaCo-2 cells with 25 muM resveratrol caused a
70% growth inhibition. The cells accumulated at the
S/G2 phase transition of the cell cycle. No signs of
cytotoxicity or apoptosis were detected. Resveratrol
caused a significant decrease of ornithine decarboxylase
(ODC) activity, a key enzyme of polyamine biosynthesis,
which is enhanced in cancer growth. ODC inhibition resulted
in the reduction of the intracellular putrescine content,
indicating that polyamines might represent one of several
targets involved in the anti-proliferative effects of
resveratrol.
PMID: 10940513
1:
Exp Mol Med 2000 Jun 30;32(2):88-92 |
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Dose-dependent effect
of resveratrol on proliferation and apoptosis in endothelial
and tumor cell cultures.
Szende B, Tyihak E, Kiraly-Veghely Z
1st Institute of Pathology and Experimental Cancer Research,
Semmelweis University, Budapest, Hungary. bszende@korb1.sote.hu
[Medline record in process]
Experimental data suggest that Resveratrol, a compound
found in grapes and other fruits may influence cell
proliferation and apoptosis. The aim of our experiments
was to study the effect of Resveratrol on tumor cell
cultures and an endothelial cell culture in order to
examine the effect of various doses of this compound
on active cell death and cell proliferation. Human tumor
(HT-29, SW-620, HT-1080) and endothelial (HUV-EC-C)
cells were treated with various doses of (0.1 to 100.0
microg/ml) Resveratrol in vitro. Cell number, apoptotic
and mitotic index was measured 24, 48 and 72 h after
treatment. Low doses (0.1-1.0 microg/ml) of Resveratrol
enhance cell proliferation, higher doses (10.0-100.0
microg/ml) induce apoptosis and decrease mitotic activity,
which is reflected in changes of cell number. Resveratrol
influences dose dependently the proliferative and apoptotic
activity of human tumor and endothelial cells. The possible
role of formaldehyde in the mechanism of action of Resveratrol
is discussed.
PMID: 10926121, UI: 20380109
1:
Biochem Biophys Res Commun 2000 Jul
21;274(1):61-7 |
|
Resveratrol inhibits
AGEs-induced proliferation and collagen synthesis activity
in vascular smooth muscle cells from stroke-prone spontaneously
hypertensive rats.
Mizutani K, Ikeda K, Yamori Y
Life Science, Environmental Conservation and Development,
Graduate School of Human and Environmental Studies,
Kyoto University, Yosida, Nihonmatu-cho, Sakyo-ku, Kyoto,
6068501, Japan.
Advanced glycation end-products (AGEs) of plasma proteins
and/or matrix proteins are candidate mediators for various
vascular complications such as atherosclerosis. We previously
reported a significantly larger accumulation of AGEs
of the aorta in stroke-prone spontaneously hypertensive
rats (SHRSP) than in age-matched Wistar-Kyoto rats (WKY).
In this study, we examined the effects of AGEs on vascular
smooth muscle cells (VSMC) from SHRSP and WKY rats.
We also studied the in vitro effects of resveratrol
(3, 4',5-trihydroxystilbene), a natural phytestrogen,
on VSMC proliferation, DNA synthesis, and collagen synthesis
activity in SHRSP-VSMC. AGEs accelerated the proliferation
of SHRSP- or WKY-VSMC in a time- and dose-dependent
manner. VSMC from SHRSP were more sensitive to AGEs
than VSMC from normotensive WKY. AGEs also significantly
increased DNA synthesis and prolyl hydroxylase activity,
a marker for collagen synthesis, in SHRSP-VSMC. AGEs-induced
increases in TGF-beta1 mRNA in SHRSP-VSMC were significantly
greater than in WKY-VSMC. Resveratrol inhibited AGEs-stimulated
proliferation, DNA synthesis, and prolyl hydroxylase
activity in SHRSP-VSMC in a dose-dependent manner. ICI
182780, a specific estrogen receptor antagonist, partly
blocked the inhibitory effects of resveratrol on AGEs-stimulated
proliferation, DNA synthesis, and prolyl hydroxylase
activity. Resveratrol significantly inhibited AGEs-induced
TGF-beta1 mRNA increases in a dose-dependent manner.
Thus, resveratrol may confer protective effects on the
cardiovascular system by attenuating vascular remodeling
and may be clinically useful as a safer substitute for
feminizing estrogens in preventing cardiovascular disease.
Copyright 2000 Academic Press.
PMID: 10903896, UI: 20365828
1:
Carcinogenesis 2000 Aug;21(8):1619-22 |
|
Resveratrol depresses
the growth of colorectal aberrant crypt foci by affecting
bax and p21(CIP) expression.
Tessitore L, Davit A, Sarotto I, Caderni G
Dipartimento di Scienze Chimiche Alimentari Farmaceutiche
e Farmacologiche, Universita del Piemonte Orientale
'Amedeo Avogadro', Vercelli, Italy. tessitor@pasteur.sluigi.unito.it
We investigated whether resveratrol (RV) affects azoxymethane
(AOM)-induced colon carcinogenesis, by administering
RV (200 microg/kg/day in drinking water) to male F344
rats for 100 days, beginning 10 days before carcinogen
treatment (two weekly doses of 15 mg/kg AOM). Aberrant
crypt foci (ACF) were isolated and proliferation, apoptosis
and expression of the cell cycle genes bax and p21 were
determined. RV significantly reduced the number of ACF/colon
[25.7 +/- 3.6 (mean +/- SEM) versus 39.4 +/- 3.3 in
controls; P < 0.01] and their multiplicity (2.7 +/-
0.3 versus 4.9 +/- 0.6 in controls; P < 0.01), and
also abolished large ACF. In RV-treated rats, bax expression
was enhanced in ACF but not in the surrounding mucosa.
In both controls and RV-treated rats, proliferation
was higher in ACF than in normal mucosa. p21 was expressed
in ACF of controls and of RV-treated rats and in normal
mucosa of controls, but was lost in normal mucosa of
RV-treated animals. In conclusion, the results suggest
a protective role of RV in colon carcinogenesis with
a mechanism involving changes in bax and p21 expression.
PMID: 10910967, UI: 20372603
1:
J Nutr Sci Vitaminol (Tokyo) 2000 Apr;46(2):78-83 |
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Resveratrol attenuates
ovariectomy-induced hypertension and bone loss in stroke-prone
spontaneously hypertensive rats.
Mizutani K, Ikeda K, Kawai Y, Yamori Y
Life Science, Environmental Conservation and Development,
Graduate School of Human and Environmental Studies,
Kyoto University, Japan.
[Medline record in process]
We examined the effect of resveratrol (3,4',5-trihydroxy
stilbene), a phenolic compound found in the skins of
most grapes, on blood pressure and bone loss in ovariectomized
(OVX), stroke-prone spontaneously hypertensive rats
(SHRSP). Nineteen-week-old female SHRSP were divided
into a sham-ovariectomized (sham) group fed a control
diet and two OVX groups fed either a control diet (OVX-Cont)
or a diet supplemented with resveratrol (5 mg/kg per
d; OVX-Resv). Ovariectomy induced significant increases
in systolic blood pressure (SBP). Resveratrol lowered
the SBP by 15%) by the third week of administration,
and this effect was maintained throughout the study.
Resveratrol treatment also significantly enhanced endothelium-dependent
vascular relaxation in response to acetylcholine (ACh)
in OVX rats. Finally, femur breaking energies measured
for the resveratrol-treated (OVX-Resv) group were significantly
higher than those of the resveratrol-untreated (OVX-Cont)
group. While no significant differences in calcium,
magnesium and phosphorus content were found between
the femurs of OVX-Cont and OVX-Resv rats, the femur
hydroxyproline content in the OVX-Resv group was significantly
higher than of the OVX-Cont group. We conclude that,
in OVX-SHRSP, resveratrol acts by a similar mechanism
to mammalian estrogens, lowering blood pressure by increasing
dilatory responses to ACh. The present study also demonstrated
that resveratrol was able to prevent ovariectomy-induced
decreases in femoral bone strength.
PMID: 10885794, UI: 20340320
1:
Br J Haematol 2000 May;109(2):405-12 |
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Resveratrol induces
Fas signalling-independent apoptosis in THP-1 human
monocytic leukaemia cells.
Tsan MF, White JE, Maheshwari JG, Bremner TA, Sacco
J
Research and Medical Services, Stratton VA Medical Center,
Albany, NY 12208, USA.
Resveratrol, a natural product present in wine, has
recently been shown to inhibit the growth of a number
of cancer cell lines in vitro. In the current study,
we have demonstrated that resveratrol inhibits the growth
of THP-1 human monocytic leukaemia cells in a dose-dependent
manner with a median effective dose of 12 microM. It
did not induce differentiation of THP-1 cells and had
no toxic effect on THP-1 cells that had been induced
to differentiate into monocytes/macrophages by phorbol
myristate acetate. A significant fraction of resveratrol-treated
cells underwent apoptosis as judged by flow cytometric
analysis of DNA content, DNA fragmentation and caspase-specific
cleavage of poly(ADP-ribosyl) polymerase. Resveratrol
treatment had no effect on the expression of Fas receptor
or Fas ligand (FasL) in THP-1 cells, nor did it induce
clustering of Fas receptors. In addition, THP-1 cells
were resistant to activating anti-Fas antibody, and
neutralizing anti-Fas and/or anti-FasL antibodies had
no protective effect against resveratrol-induced inhibition
of THP-1 cell growth. The effect of resveratrol on THP-1
cells was reversible after its removal from the culture
medium. These results suggest that (1) resveratrol inhibits
the growth of THP-1 cells, at least in part, by inducing
apoptosis, (2) resveratrol-induced apoptosis of THP-1
cells is independent of the Fas/FasL signalling pathway
and (3) resveratrol does not induce differentation of
THP-1 cells and has no toxic effect on differentiated
THP-1 cells. Thus, resveratrol may be a potential chemotherapeutic
agent for the control of acute monocytic leukaemia.
PMID: 10848832, UI: 20308123
1:
Cancer Detect Prev 1997;21(1):71-7 |
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Effect of Krestin as
adjuvant treatment following radical radiotherapy in
non-small cell lung cancer patients.
Hayakawa K, Mitsuhashi N, Saito Y, Nakayama Y, Furuta
M, Nakamoto S, Kawashima M, Niibe H
Department of Radiology and Radiation Oncology, Gunma
University School of Medicine, Japan.
To evaluate the efficacy of Krestin (PSK) as adjuvant
treatment after radical radiation therapy (RT) for non-small
cell lung cancer (NSCLC), treatment results of 225 patients
with NSCLC treated with RT followed by adjuvant administration
of PSK between 1976 and 1989 were analyzed. Of these
patients, 170 (76%) had squamous cell carcinoma. In
the patients with squamous cell carcinoma of the lung,
PSK was given only when the tumor showed satisfactory
shrinkage (complete or partial response) after completion
of RT. The treatment outcomes were compared with those
of the responders to RT not receiving PSK. The 5-year
survival rates of patients with stages I-II and stage
III disease were 39 and 26%, respectively, while the
non-administered responder group's were 17 and 8%. These
differences are statistically significant. An improvement
in the treatment results with combined use of appropriate
immuno-modulating drugs is anticipated in the future.
When clinical trials of the efficacy of these drugs
are conducted, the agents should be given to the patients
with satisfactory tumor regression after RT, although
they still take much time and cost.
Publication Types:
Clinical trial
PMID: 9043766, UI: 97196677
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