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[Fred_CALICO]

<p>  LatruffeEJMC.pdf   825.19KB   1 downloadsI start a new thread to avoid cluttering the initial wire<br />
( <a class="bbc_url" href="http://www.longecity...e/#entry552491" title="">here</a> )<br />
I would develop later because now I have to test in vivo the Corbiere wine.<br />
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Online article (version 1) in english : <a class="bbc_url" href="http://hal.archives-...truffeEJMC.pdf" rel="nofollow external" title="External link">http://hal.archives-...EJMC.pdf</a><br />
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Doctoral thesis in french<br />
<a class="bbc_url" href="http://ressources-nu...ERIC_00_00.pdf" rel="nofollow external" title="External link">http://ressources-nu...0_00.pdf</a><br />
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<img src="https://docs.google....zJaelEyZDVqN0k" />&nbsp;&nbsp; <a class="bbc_url" href="https://docs.google....zJaelEyZDVqN0k" rel="nofollow external" title="External link">https://docs.google....yZDVqN0k</a><br />
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<img src="https://docs.google....lFabGdnMWc5ZjQ" />&nbsp;&nbsp;&nbsp;&nbsp;<a class="bbc_url" href="https://docs.google....lFabGdnMWc5ZjQ" rel="nofollow external" title="External link">https://docs.google....nMWc5ZjQ</a><br />
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Early summary :<br />
Complex natural mixtures of red wine polyphenols show their ability to stop the proliferation of cancer cells in vitro. But this slowdown seems less specifically related to a blockage in one particular phase of the cell cycle, as can be seen with resveratrol or quercetin for example, but rather an overall slowdown in all phases of the cell cycle. The diversity of phenolic compounds present in wine and diversity of activities are also an argument in favor of this hypothesis. Each of these molecules using multiple channels and each channel is used by several molecules, red wine polyphenols may together form a mesh and biological pathways of great complexity. Synergistic effects may exist between certain molecules in some ways, but also contradictory effects, as we have seen with combinations of resveratrol, quercetin and catechin on HCT116 cells. We have not clearly demonstrated strong synergy of actions of wine polyphenols on a specific mechanism, but this study has revealed a set of effects (such as<br />
antiproliferative synergy between resveratrol and quercetin) that individually could be considered minimal, but which together combine to inhibit the proliferative activity of tumor cells.<br />
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Concentrates and extracts all exhibit antiproliferative capacity of cells SW480 human colon cancer from. The inhibition of proliferation is correlated with the total polyphenol concentration for the same wine. The extract appears wine Corbières able to act effectively in relatively low doses. Although variations in sensitivity between different cells tests make it impossible for a direct comparison with experimental wines of Burgundy, it seems that this extract Corbières wine is much more efficient in terms of inhibition of cell proliferation. Should be Repeat testing in similar conditions to clarify this point.<br />
In addition, extracts of Burgundy wines of 2008 and 2009 do not have the same capabilities at antiproliferative concentrations of polyphenols equal. Wines that have undergone the maceration longest show an inhibitory power more important. If the IC50 is not correlated perfectly with the maceration time, these variations indicate all of well as the quality of polyphenols is an essential element in their effectiveness. Wines and the most effective are those whose contents gallic acid, catechin and epicatechin are the most important.<br />
Cancer cells are sensitive to resveratrol and quercetin, which may act synergistically in limiting their proliferation. This inhibition is at least partly due to blocking S phase of the cell cycle, but studies of the cell cycle does not explain the synergistic 133effets. Low concentrations used in these tests do not induce cell death real either by necrosis or apoptosis, this mechanism does not seem to be taken into account to explain the decrease in the number of cells.<br />
Paradoxically, wines with the lowest levels of quercetin and resveratrol are those for which we observed the best efficiencies against the antiproliferative<br />
SW480 cells.</p>

[Fred_CALICO]

Discussion of the article and the new work published
since the publication of the article 2010

3,4 ',5-trimethoxy-cis-stilbene in particular, has very powerful effects in vitro in our study and in others, proves however fairly active in vivo
contrast to 3,4 ',5-trimethoxy-trans-stilbene (Paul et al., 2010) which in our model revealed an antiproliferative efficiency lower than that of resveratrol. The same 3,4 ', 5 -
trimethoxy-trans-stilbene seems nevertheless involve different mechanisms of resveratrol (Hsieh et al., 2011) can promote apoptosis in particular cells
cancer.

The presence of para-groups are often portrayed as dominant in the effects due to different analogues of trans-resveratrol, the
molecules bearing hydroxyl or methoxyl in positions 4 and 4 'are the subject of special attention. This is the case of 3,4,5,4 '-tetramethoxy-trans-stilbene (DMU-
212) and its derivatives produced in vivo by hydroxylation and demethylations (Androutsopoulos et al., 2011). The presence of methoxyl groups in 4 or 4 'actually proves decisive for the anti-tumor activity of stilbene. other
studies have also focused on another compound particularly active in vivo: the 3,4,5,3 ', 4', 5'-hexahydroxy-trans-stilbene (M8) (Szekeres et al., 2010).
Comparative studies between resveratrol and its natural or synthetic derivatives are still relevant and provide many avenues in control strategies
against cancer (Yen and Weng, 2011).

[Fred_CALICO]

A. Wine, food to share or a share of food?

It is commonly accepted that to be healthy, you must eat healthily.
The public interest in a healthy diet is evident from numerous publications dealing with all types of nutrition or diet (Willett et al., 2001). Foods that are put forward, there is wine, whether to promote it or criticize it. The wine has been considered since the beginning of civilization as a food beneficial to health, or even a drug (Lucia, 1972).

1. The value of a contribution in wine
The wine is an important contribution of antioxidants and free-radical scavengers, and even during the winter when they normally default. The wine is mainly consumed by
pleasure and as part of usability. It can also be an energy intake. But the indirect benefit of such consumption was in ancient times bearing deficiency
fruits and vegetables out of season cultivation. This can be seen in wine consumption as a nutritional course. Today in rich countries
you can find sources of antioxidants even when not cultivated through the provision of technology, greenhouse crops, and international trade.
Nevertheless, it is in our country we find the highest rates of colon cancer, the cause is mainly due to a poor diet and the presence of mutagens in foods (Goldman and Shields, 2003; Sutandyo , 2010). An additional polyphenols through the wine can not be useless.

2. Nutritional context
The benefits of moderate consumption of red wine on health should be considered in a complete diet. And wine is part of the full regime
Mediterranean (Hu, 2003), which is also rich in vegetables, fruits, seeds and olive oil.
These foods are particularly important sources of various phenolic compounds.
White wine could also be taken into consideration, power cardio at least, due to tyrosol, was considered comparable to that of resveratrol (Dudley et al., 2008). In France, the main sources of polyphenols in the diet are apples and potatoes (Brat et al., 2006). We saw the wine polyphenols are able to interact with each other, but if you replace the wine consumption in the context of a normal diet, it is therefore necessary to consider
also all other compounds provided by other foods. All these plants are indeed rich in bioactive compounds such as polyphenols, but also others such
that the fibers or polyunsaturated fatty acids. These molecules are classified as bioactive because of their actions on the body and have for many a role in
prevention of many diseases (Kris-Etherton et al., 2002). Several phenolic compounds have shown proven chemopreventive effects against primary tumors or
metastases (Yen and Weng, 2011). In addition to acting side-by-side, some polyphenols combinations may show synergistic effects. For example, the acid
ellagic polyphenol present in many foods (chestnuts, raspberries, strawberries, cranberries, walnuts, pecans, pomegranates, ...), is able to act synergistically with
quercetin to reduce proliferation and induce apoptosis of human leukemia cells MOLT-4 (Mertens-Talcott et al., 2003). This mechanism involving activation
the channel p21 WAF1/Cip1 / p53 / MAPK (Mertens-Talcott and Percival, 2005).

3. Wine, liquor
If red wine polyphenols have shown protective effects against cancer, it seems clear that ethanol is a factor aggravating mainly from a dose
equivalent to two to three glasses of wine per day (Guo and Ren, 2010) and perhaps lower doses from a single glass of wine per day for breast cancer as suggested
one recent prospective observational study (Chen et al., 2011). This latter study, however, was immediately questioned (Narod, 2011), mainly due
that the protective effects of moderate consumption (2 glasses per day) of red wine against atherosclerosis and cancer brings a significant improvement of hope
life (Renaud et al., 1998). If the deleterious effects of high consumption seem obvious, it is questionable that moderate wine consumption protects
against cancer in general. In vivo tests in mice have shown, however, that the adverse effects of ethanol on some neurological parameters were not observed with wine consumption equivalent amount of ethanol (Fiore et al., 2009) and even that a moderate wine consumption had a protective effect against the
dementia in the elderly (Orgogozo et al., 1997). The disadvantages of ethanol are minimized when the wine, its adverse effects are neutralized by
antioxidant effects of polyphenols (Opie and Lecour, 2007). Conversely, it seems possible that the health benefits of wine consumption may not be optimal because
ethanol.
Note: The alcohol content of wine seems to be required to increase as projected by global warming. This increase in alcoholic strength is therefore
not desirable from a medical, but also on the commercial, light wines being increasingly popular. Indeed, consumers are increasingly attracted by
wines with low alcohol content, for many reasons. First taste, Constant Bourquin, founder member of the International Wine Academy said the same:
"I see an advantage and even an advantage to not like wine that gluttony, and therefore, not being at all attracted (and this is my case) by alcohol.
If it were possible that a good wine was the equivalent of what it is without contain alcohol, without hesitation, I would lover that wine. But wine is wine, because of its natural alcohol content. Then I'm bow and a reason. Feeling that I could express how Anatole France: Alas, willingly. " Then for economic reasons with a share of taxes more pressing, and other repressions of increasingly restrictive for drivers, the wine industry could be brought in the near future to rethink vinification processes to reduce the alcohol content
wines. Several approaches are possible (limiting fermentation, using yeast fermentation capacity low, decrease the temperature, eliminate sugars before fermentation or eliminate the ethanol-reverse osmosis), but none of these techniques has the time yielded red wines of sufficient quality to be able to consider
an alternative to wines to alcoholic content higher than 10%. Or low alcohol wines and alcoholized products are indeed often unpleasant and bitter in the mouth.

4.Apport our results in this issue

Our in vivo tests in mice using a concentrated wine incorporated into the diet.
Ethanol-free, concentrated wine that showed no significant changes in weight gain of the animals. It might be interesting to observe the effects of such
treatment of animals suffering from fat storage or fed diets high in fats and sugars. Indeed, resveratrol has recently been described
as capable of restoring normal lipid metabolism deregulated (Baur et al., 2006; Feige et al., 2008; Dal-Pan et al., 2010). Obesity is linked to the process
inflammatory, it is logical to think that red wine polyphenols could also act against metabolic diseases (Chuang and McIntosh, 2011).
A clinical study conducted by our laboratory (Rifler et al., 2011) shows a secondary preventive effect real moderate consumption of red wine of Burgundy
several blood parameters associated with cardiovascular disease. The patients included in this study had all suffered myocardial infarction. They also received a Mediterranean-style diet. Compared to the control group drinking only water, the group receiving 250 mL of red wine per day has, after only two weeks of monitoring, cholesterol decreased, particularly in regard to LDL, an increase in blood antioxidant status and improved membrane fluidity of erythrocytes.

[Fred_CALICO]

B. Cancer chemoprevention by compounds
wine phenolics

Among the phenolic compounds in red wine, several molecules showed chemopreventive abilities or at least positive actions at different levels of
carcinogenesis (initiation, promotion, progression) or even the ability to limit upstream action of carcinogens on cells. And resveratrol in particular was the
subject of many studies concluding that it is a potent chemopreventive agent (Liu et al., 2007) able to specifically induce apoptosis of cancer cells while protecting healthy cells (Baarine et al., 2011). But it is also the case of other molecules such as gallic acid (Giftson Senapathy et al., 2011) or quercetin (Lee et al., 2008). These preventive effects are still very variable in vitro and in vivo fortiori (Soleas et al., 2001).

1. Combinations of bioactive molecules

While many beneficial effects of these isolated compounds are shown, they are still relatively modest after ingestion. For example, many polyphenols have been shown
as able to inhibit CYP1A1, an enzyme of phase I metabolism of xenobiotics, but at doses several microM (Schwarz and Roots, 2003). One way to increase this efficiency would be to administer combinations of polyphenols (Russo, 2007). Studies have shown positive interactions between synergistic see some molecules, as we have also seen with the combination of resveratrol and quercetin in particular.
If combinations of two or three compounds can be effective in chemoprevention, combinations of a large number of compounds may represent an even more optimal. However, as we have seen, it is difficult to establish a comprehensive mapping of interaction mechanisms of action of these polyphenols, and create mixtures of any part is extremely complex. The most logical approach is then from complex mixtures existing and possibly optimize the anti-carcinogenic effects by modulating the concentrations of certain specific polyphenols key only. A natural mixtures that present efficiencies chemopreventive most important is the red wine (He et al., 2008), but can also include extracts from grape skin (Hudson et al., 2007), extracts seeds
Grape (Velmurugan et al., 2010), extracts of milk thistle (Silybum marianum) and Ginkgo biloba (El Mesallamy et al., 2011). Extracts of grape seed artificially
enriched with resveratrol have a pro-apoptotic activity particularly important on colorectal cancer cells (Radhakrishnan et al., 2011).
Concentrate our Burgundy wine was also able to protect against the occurrence of pre-neoplastic lesions in mouse colon. In particular, it reduces the number of aberrant crypt foci and especially those of large sizes that are considered good indicators of carcinogenesis.
At present the best approach to chemoprevention that could be proposed is the most simple: eat a healthy, varied and rich in polyphenols (Scalbert et al., 2005).
2. Chemical changes of phenolic compounds
Changes in the chemical structure of polyphenols may be a promising way to overcome the shortcomings. Resveratrol and normally has a
low bioavailability, lower than that of pterostilbene, a natural derivative of the nearest is also a chemopreventive agent (Rimando et al., 2002). The addition of
methoxyl groups can therefore gain bioavailability but potentially altering antitumor activity. Based on this observation, many analogues
resveratrol or other aromatic compounds were synthesized, adding methoxyl groups, acétoxyles, hydroxyl or other on the phenolic rings. These various groups including lower hydrophobicity of the molecules.
This approach has helped to develop a number of drugs such as inhibitors of Cdc25 based on coumarins (Valente et al., 2010),
antiproliferative agents derived from epicatechin-3-gallate (Sanchez-del-Campo et al., 2008) or analogues of resveratrol (Saiko et al., 2008) such as those on which we worked (Mazué et al. 2010).
Structural changes of different polyphenols may also be produced by cells via the metabolism of xenobiotics and present potentially significant anticancer effects. It is even possible that some of these metabolites are biologically more active than molecules from which they derive (Forester and Waterhouse, 2009).
It is in the context of understanding the anticancer activity of resveratrol metabolites that some tests are being conducted in our laboratory.

C. General conclusion and perspectives

Through this work we evaluated the overall capacity of red wine polyphenols inhibit cell proliferation of colon cancer or liver and their
impact on the metabolism of a polyphenol in particular resveratrol. Concentrates and extracts of red wines of Burgundy with maceration time and different vintages all showed dose-dependent activity ntiprolifératives-dependent and qualitative in vitro cell lines of colorectal cancer. In some
conditions, we also showed that a combination of wine polyphenols and resveratrol was antiproliferative treatments that one or the other separately.
This additivity is found not follow a simple but be the sum of interactions between different polyphenols, whether synergy (resveratrol and
quercetin) or partial additivity, or even antagonism (catechin and quercetin with resveratrol). One of the possible mechanisms involved in these interactions for the modulation of membrane transport of polyphenols and their metabolism by cells. We could also highlight the possible preventive effects of
wine polyphenols on precancerous intestinal outbreaks in animals. The complexity of these interactions and intracellular mechanisms involved for many
all red wine polyphenols suggest a pattern of action unpredictable. In addition to the direct action of polyphenols present in wine, it is also
consider the effects of metabolites produced by the cells through detoxification enzymes of xenobiotics.
Studies undertaken in this thesis have highlighted some points that we must now try to clarify. In particular it will be necessary to continue the study on
modulatory effects of red wine polyphenols on metabolism detoxification of resveratrol in phases II and III.
And further assays quantities of resveratrol metabolized by HepG2 and SW480 cells seems in our opinion the first priority. Preliminary tests have allowed us
validate our detection protocol, and a trend towards a decrease in the metabolism of resveratrol in the presence of wine, further tests prove feasible and desirable. To quantify these metabolites accurately, it should initially perform standard ranges with the standards of
various derivatives of resveratrol.
The study of phase III enzymes at the cellular level will also be pursued in the coming months. QPCR will assess the changes in expression levels of the enzymes of phases II and III. Blottings westerns (transfer protein and immunodécoration) will assess the relative amounts of these enzymes.
On the in vivo study using concentrated wines of Burgundy, the presence of polyphenols in the blood and tissues of animals will be sought by assaying Folin-
Ciocalteu and optionally by HPLC. Of qPCR will be performed to study the expression of certain genes involved in carcinogenesis and metabolism of xenobiotic detoxification in liver and colon tissues. In the longer term, another study could be considered with a higher number of animals used and longer periods that would allow the development of pre-neoplastic lesions or even more advanced adenocarcinomas.

[maxwatt]

This becomes a problem in combinatorial mathematics; besides the unknowns concerning action of a single compound, the operative effect of combinations of these substances and their interaction with each other are also unknown. It will be difficult to sort out, no less so because of genetic variability in human and mouse subjects adding another order of complexity. Then differences in wine, varieties, grapes, growing seasons, terroir and more. Perhaps we can eventually sort things out but this is a start,

[Fred_CALICO]

Perhaps we are looking under the lamppost ... choose your wine with his nose ... the brain is a great calculator combinations.
Do not exceed the prescribed dose ltrop often.
Scientifically some guidelines emerge from such studies.

[Fred_CALICO]

http://www.ncbi.nlm....dna resveratrol


Many sources Pubmed benefits of Propolis.

Why not potentiate the benefits of wine polyphenols to those of propolis?

Pour a few drops of propolis extracts in the wine glass.
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Resveratrol and propolis as necrosis or apoptosis inducers in human prostate carcinoma cells.

Scifo C, Cardile V, Russo A, Consoli R, Vancheri C, Capasso F, Vanella A, Renis M.

Source

Department of Biological Chemistry, Medicinal Chemistry and Molecular Biology, University of Catania, Viale Andrea Doria, 6, 95125 Catania, Italy.

Abstract

Vegetables and fruit help the prevention and the therapy of several kinds of cancer because they contain micronutrients, a class of substances that have been shown to exhibit chemopreventive and chemotherapeutic activities. In the present study the effects of resveratrol (100 and 200 microM), a phytoalexin found in grapes, and of the ethanolic extract of propolis (50 and 100 microg/ml), a natural honeybee hive product, were tested in androgen-resistant prostate cancer cells (DU145), a cell line resembling the last stage of prostate carcinoma. A comparison between the activity of these micronutrients and vinorelbine bitartrate (Navelbine), a semi-synthetic drug normally used in the therapy of prostate cancer, was conducted. Several biochemical parameters were tested, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), cell redox status (nitric oxide formation, reactive oxygen species production, reduced glutathione levels), genomicDNA fragmentation (COMET assay) with special attention on the presence of apoptotic DNA damage (TUNEL test), and possible mitochondrial transmembrane potential alteration (deltapsi). Our results point out the anticancer activity of resveratroland propolis extract in human prostate cancer, exerting their cytotoxicity through two different types of cell death: necrosis and apoptosis, respectively. The data obtained suggest the possible use of these micronutrients both in alternative to classic chemotherapy, and in combination with very low dosage of vinorelbine (5 microM).

PMID: 15490973 [PubMed - indexed for MEDLINE]