Download Flavanols and Breast Cancer

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Breast cancer and flavonoids - a role in prevention.
Takemura H1, Sakakibara H, Yamazaki S, Shimoi K.
Author information
Institute for Environmental Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
[email protected].
Abstract
Endogenous estrogens, such as 17β-estradiol (E2), are implicated in the development of breast cancer.
The putative mechanisms by which estrogens exert the carcinogenic effects have been recognized to
involve the redox cycling of estrogen metabolites and subsequent estrogen-DNA adduct formation as
well as the estrogen receptor-dependent pathway of estrogen-induced cell growth. The former pathway
is regulated by phase I enzymes, mainly cytochrome P450 (CYP) 1A1, 1A2, and 1B1. Among them,
CYP1B1 predominantly catalyzes the C4-position of E2 and forms carcinogenic 4-hydroxy-E2 (4-OHE2),
whereas CYP1A1 and CYP1A2 convert E2 to non-carcinogenic-hydroxy-E2. Formed 4-OHE2 is further
oxidized to semiquinones and quinones, which form DNA adducts, leading to mutagenic lesions.
Consequently, CYP1B1 is highly expressed, and 4-OHE2 is predominantly detected in estrogen target
neoplastic tissues. Moreover, invasion and metastasis are also involved in the development of breast
cancer. Epidemiological studies suggest an inverse association between a higher intake of flavonoids
and breast cancer risk. Flavonoids, which are widely distributed in the plant kingdom, have been
recently reported as candidate compounds that can exert chemo preventive effects in estrogendependent or independent breast cancer.
In this review, we provide a comprehensive overview of breast cancer and chemoprevention by
flavonoids, mainly focusing on ER-mediated hormonal regulation, redox cycling of estrogen metabolites,
and selective inhibition of CYP1B1.
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Green Tea (Flavanols content)
One study looked at 472 women in various stages of breast cancer (labeled 1, II, or III, depending on
how far the cancer had progressed). Increased green-tea consumption was associated with a decreased
risk of lymph node metastasis in premenopausal women with stages I and II cancer. The researchers also
found that if women with these stages of breast cancer consumed 5 cups a day of green tea on a longterm basis, they were more likely to be in remission 6 months later when the follow-up study was done.
- The Natural Physician's Healing Therapies by Mark Stengler, N.D. ( Available on Amazon.com)
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In test tube studies, green tea shut
down the tumor promoters involved in breast cancer. Green
tea inhibits the formation of cancer-causing agents in the stomach, including nitrosamines. The anticancer properties of green tea include: Immune stimulant. Inhibits platelet adhesion, and possibly
metastasis. Antioxidant which protects immune cells for a higher tumor kill rate while protecting the
valuable prostaglandin PGE-1. Inhibits metastasis. Inhibits the breakdown of connective tissue via
collagenase, which is the primary mechanism for the spreading of cancer cells.
- Beating Cancer with Nutrition by Patrick Quillin, PhD,RD,CNS
- Available on Amazon.com
http://www.naturalnews.com/025687_green_tea_breast_cancer.html#ixzz4DwnMBBHV
Antitumor activity of the novel flavonoid Oncamex in preclinical breast cancer models
British Journal of Cancer (2016) 114, 905–916. doi:10.1038/bjc.2016.6 www.bjcancer.com
Published online 31 March 2016
Authors: Carlos Martínez-Pérez, Carol Ward, Arran K Turnbull, Peter Mullen, Graeme Cook,
James Meehan, Edward J Jarman, Patrick IT Thomson, Colin J Campbell, Donald McPhail, David J
Harrison & Simon P Langdon
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Myricetin as the active principle of Abelmoschus moschatus to lower plasma glucose in
streptozotocin-induced diabetic rats.
Planta Med. 2005. Department of Pharmacy, Tajen Institute of Technology, Yen-Pou, Ping Tung
Shien, Taiwan,.
The antihyperglycemic action of myricetin, purified from the aerial part of Abelmoschus
moschatus (Malvaceae), was investigated in streptozotocin-induced diabetic rats. These results
suggest that myricetin has an ability to enhance glucose utilization to lower plasma glucose in
diabetic rats lacking insulin.
Anti-inflammatory health use
Anti-inflammatory Activity of Myricetin Isolated from Myrica rubra Sieb. et Zucc. Leaves.
Planta Med. 2010. Department of Pharmaceutics, Shenyang Pharmaceutical University,
Shenyang, PR China.
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MYRICA RUBRA leaves are
commonly used in folk medicine to treat inflammatory
disorders in China. Present studies on the anti-inflammatory effect of myricetin from MYRICA
RUBRA Sieb leaves was evaluated with various IN VIVO models of both acute and chronic
inflammations such as xylene-induced ear edema, acetic acid-induced vascular permeability,
carrageenan-induced paw edema, leukocyte migration assay, and cotton pellet granuloma
models.
Myricetin showed a significant inhibition on ear edema and hind paw edema caused by xylene
and carrageenan, respectively. Our results also support the claims of traditional Chinese
medicine practitioners about the use of MYRICA RUBRA leaves in the treatment of
inflammatory diseases.
Inhibition of interleukin-12 production in mouse macrophages via decreased nuclear factorkappaB DNA binding activity by myricetin, a naturally occurring flavonoid. Arch Pharm Res.
2005.
Pharmacological inhibition of interleukin-12 (IL-12) production may be a therapeutic strategy
for preventing the development and progression of disease in experimental models of
autoimmunity. In this study, the effects of myricetin, a naturally occurring flavonoid present in
fruits, vegetables and medicinal herbs, on the production of IL-12 were investigated in mouse
macrophages stimulated with lipopolysaccharide (LPS). Myricetin significantly inhibited the LPSinduced IL-12 production from both primary macrophages and the RAW264.7 monocytic cellline in a dose-dependent manner. The effect of myricetin on IL-12 gene promoter activation
was analyzed by transfecting RAW264.7 cells with IL-12 gene promoter/luciferase constructs.
Furthermore, activation of macrophages by LPS resulted in markedly enhanced binding activity
to the NF-kappaB site, which significantly decreased upon addition of myricetin, indicating that
myricetin inhibited IL-12 production in LPS-activated macrophages via the down-regulation of
NF-kappaB binding activity.
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Cancer protection
Life Sci. 2015. Molecular mechanisms underlying anticancer effects of myricetin. Dietary
guidelines published in the past two decades have acknowledged the beneficial effects of
myricetin, an important and common type of herbal flavonoid, against several human diseases
such as inflammation, cardiovascular pathologies, and cancer. An increasing number of studies
have shown the beneficial effects of myricetin against different types of cancer by modifying
several cancer hallmarks including aberrant cell proliferation, signaling pathways, apoptosis,
angiogenesis, and tumor metastasis. Most importantly, myricetin interacts with oncoproteins
such as protein kinase B (PKB) (Akt), Fyn, MEK1, and JAK1-STAT3 (Janus kinase-signal transducer
and activator of transcription 3), and it attenuates the neoplastic transformation of cancer cells.
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Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells.
Biochem Pharmacol. 2005. The Prevention Program, Barbara Ann Karmanos Cancer Institute,
School of Medicine, Wayne State University, Detroit, MI
It has been shown that proteasome activity is required for cancer cell survival and consumption
of fruits and vegetables is associated with decreased cancer risk. In this study, we examined the
flavonoids quercetin, apigenin, myricetin, and kaempferol for their proteasome-inhibitory and
apoptosis-inducing abilities in human tumor cells. We report that apigenin and quercetin are
much more potent than kaempferol and myricetin at: (i) inhibiting chymotrypsin-like activity of
purified 20S proteasome and of 26S proteasome in intact leukemia Jurkat T cells; (ii)
accumulating putative ubiquitinated forms of two proteasome target proteins, Bax and
Inhibitor of nuclear factor kappabeta-alpha in Jurkat T cells and (iii) inducing activation of
caspase-3 and cleavage of poly(ADP-ribose) polymerase in Jurkat T cells. The proteasomeinhibitory abilities of these compounds correlated with their apoptosis-inducing potencies.
Results from computational modeling of the potential interactions of these flavonoids to the
chymotrypsin site (beta5 subunit) of the proteasome were consistent with the obtained
proteasome-inhibitory activities. We found that the C (4) carbon may be a site of nucleophilic
attack by the OH group of N-terminal threonine of proteasome beta5 subunit and that the C(3)
hydroxyl may alter the ability of these flavonoids to inhibit the proteasome. Finally, apigenin
neither effectively inhibited the proteasome activity nor induced apoptosis in non-transformed
human natural killer cells. Our results suggested that the proteasome may be a target of these
dietary flavonoids in human tumor cells and that inhibition of the proteasome by flavonoids
may be one of the mechanisms responsible for their cancer-preventive effects.
Myricetin Induces Cell Death of Human Colon Cancer Cells via BAX/BCL2-Dependent Pathway.
Anticancer Res. 2014 Feb.
Diabetes
J Med Food. 2013. Effect of Emulin on blood glucose in type 2 diabetics. Emulin is a patented
blend of chlorogenic acid, myricetin, and quercetin ( myricetin and quercetin are naturally
ingredients content in each Flavanoplus blends) that has shown efficacy in reducing midday and
post-oral glucose tolerance test (OGTT) area under the curve (AUC) glucose in streptozotocintreated rats. This human trial results suggest that Emulin, if consumed regularly, could not only
have the acute effect of lowering the glycemic impact of foods, but chronically lower
background blood glucose levels of type 2 diabetics.
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Estrogenic effect
Toxicol Lett. January 29 2014. The estrogenic effects of apigenin, phloretin and myricetin based
on uterotrophic assay in immature Wistar albino rats. Chemicals that occur in vegetal food and
known as phytoestrogens, because of their structures similarity to estrogen, have benefits on
chronic diseases. Despite this, when they are taken at high amounts, they can cause harmful
effects on endocrine system of human and animals. In this study, it has been intended to
determine the estrogenic potencies of phytoestrogens apigenin, phloretin and myricetin whose
affinities for estrogen receptors in vitro. The female rats divided into 17 groups, each containing
6 rats. There was a negative control group and there were positive control dose groups which
contains ethinyl estradiol, ethinyl estradiol+tamoxifen and genistein. The other dose groups
which were tested for estrogenic activity contains apigenin, myricetin and phloretin All
chemicals have been given to Wistar immature female rats with oral gavage for 3 consecutive
days. By using uterotrophic analysis, uterus wet and blotted weights, vaginal opening, uterus
length of female rats has been recorded at the end of the experiment. For detect of cell
response, luminal epithelium height, gland number and lactoferrin intensity in luminal
epithelium of uterus were evaluated. Biochemical analysises in blood were performed. Relative
uterus weights of rats in 100mg/kg/day dose group of myricetin were statistically increased
according to vehicle control and positive control groups. In dose groups of apigenin and
phloretin it was found that there were cell responses in uterus. All treatment groups had a
significant difference in the high intensity of lactoferrin and uterine gland count compared to oil
control group. There was no difference between phloretin and apigenin treatment groups in
uterine weight statictically. Uterine heights were increased in positive control groups and
100mg/kg/day dose group of myricetin. Epithelial cell heights were increased in treatment
groups except apigenin and phloretin dose groups. There was no difference between all
treatment groups in vaginal opening values according to positive control.
Sleep influence
Biochem Biophys Res Commun. 2013 Oct 18. The flavonoid myricetin reduces nocturnal
melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase.
Preformed beta-amyloid fibrils are destabilized by coenzyme Q10 in vitro. Biochem Biophys Res
Commun. 2005.
Inhibition of the formation of beta-amyloid fibrils (fAbeta), as well as the destabilization of
preformed fAbeta in the CNS, would be attractive therapeutic targets for the treatment of
Alzheimer's disease. We reported previously that nordihydroguaiaretic acid (NDGA) and winerelated polyphenol, myricetin, inhibit fAbeta formation from Abeta and destabilize preformed
fAbeta in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron
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microscopic studies, we examined the effects of coenzyme Q10 (CoQ(10)) on the formation,
extension, and destabilization of fAbeta at pH 7.5 at 37 degrees C in vitro. We next compared
the anti-amyloidogenic activities of CoQ10 with NDGA and myricetin. Coenzyme Q10 dosedependently inhibited fAbeta formation from amyloid beta-peptide (Abeta), as well as their
extension. Moreover, it destabilized preformed fAbetas. The anti-amyloidogenic effects of
Coenzyme Q10 were slightly weaker than those of NDGA and myricetin. Coenzyme Q10 could
be a key molecule for the development of therapeutics for Alzheimer's disease.
Anthocyanins, Flavanols, and free radical scavenging activity of Chinese bayberry (Myrica rubra)
extracts and their color properties and stability. J Agric Food Chem. 2005.
Characterization of anthocyanins and flavonols and radical scavenging activity assays of extracts
from four Chinese bayberry (Myrica rubra) varieties with different fruit colors were carried out.
One dominant anthocyanin and three major flavonols were isolated by HPLC, and cyanidin-3-Oglucoside and two of three flavonols, myricetin and quercetin-3-O-rutinoside, were identified
by clochromatography with authentic standards. Both DPPH* and ABTS*(+) cation assays
indicated that the black varieties (Biji and Hunan) demonstrated much higher radical scavenging
activities than the pink (Fenhong) and yellow (Shuijing) varieties, which may be attributed to
much higher levels of anthocyanins, flavonoids, and total phenolics in the black varieties.
Myricetin inhibits matrix metalloproteinase protein expression and enzyme activity in
colorectal carcinoma cells. Mol Cancer Ther. 2005.
Because the activation of matrix metalloproteinases (MMP) is a key factor in the metastatic
process of colon cancer, agents with the ability to inhibit MMP activity have potential in the
treatment of colorectal carcinoma. In the present study, among 36 flavonoids examined,
myricetin was found to be the most potent inhibitor of MMP-2 enzyme activity in COLO 205
cells. Results of the present study indicate that myricetin significantly blocked both endogenous
and TPA-induced MMP-2 enzyme activity by inhibiting its protein expression and enzyme
activity. The blockade involved suppression of PKC translocation, ERK phosphorylation, and cJun protein expression.
Cactus Botanic introduces Myricetin extracted from Bayberry Bark
Myricetin is a flavonoid that is commonly found in natural food sources such as berries,
vegetables, teas, wine and herbs. Myricetin is considered to be an antioxidant, which means
that it is capable of eliminating free radicals within the body. It is usually taken from the bark,
leaves, and roots of the plant known as myrica cerifera, and is completely water soluble, which
means it makes an excellent source for teas. Cactus Botanics introduces Myricetin 80%, tested
by HPLC.
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