06 May 2014 In Phenolic compounds

Agents to counteract acquired resistance to hormonal therapy for breast cancer would substantially enhance the long-term benefits of hormonal therapy. In the present study, we demonstrate how resveratrol (Res) inhibits human breast cancer cell proliferation, including MCF-7 tamoxifen-resistant cells (IC(50) values for viability were in the 30-45 muM range). We show that Res, through p38(MAPK) phosphorylation, causes induction of p53, which recruits at the estrogen receptor alpha (ERalpha) proximal promoter, leading to an inhibition of ERalpha expression in terms of mRNA and protein content. These events appear specifically p53 dependent, since they are drastically abrogated with p53-targeting siRNA. Coimmunoprecipitation assay showed specific interaction between p53, the Sin3A corepressor, and histone deacetylase 1 (HDAC1), which was phosphorylated. The enhancement of the tripartite complex p53/Sin3A/HDAC1, together with NF-Y on Res treatment, was confirmed by chromatin immunoprecipitation analyses, with a concomitant release of Sp1 and RNA polymerase II, thereby inhibiting the cell transcriptional machinery. The persistence of such effects in MCF-7 tamoxifen-resistant cells at a higher extent than parental MCF-7 cells addresses how Res may be considered a useful pharmacological tool to be exploited in the adjuvant settings for treatment of breast cancer developing hormonal resistance.

06 May 2014 In Phenolic compounds

Although excessive consumption of ethanol in alcoholic beverages causes multi-organ damage, moderate consumption, particularly of red wine, is protective against all-cause mortality. These protective effects could be due to one or many components of the complex mixture of bioactive compounds present in red wine including flavonols, monomeric and polymeric flavan-3-ols, highly colored anthocyanins as well as phenolic acids and the stilbene polyphenol, resveratrol. The therapeutic potential of resveratrol, firstly in cancer chemoprevention and then later for cardioprotection, has stimulated many studies on the possible mechanisms of action. Further indications for resveratrol have been developed, including the prevention of age-related disorders such as neurodegenerative diseases, inflammation, diabetes, and cardiovascular disease. These improvements are remarkably similar yet there is an important dichotomy: low doses improve cell survival as in cardio- and neuro-protection yet high doses increase cell death as in cancer treatment. Fewer studies have examined the responses to other components of red wine, but the results have, in general, been similar to resveratrol. If the nonalcoholic constitutents of red wine are to become therapeutic agents, their ability to get to the sites of action needs to be understood. This mini-review summarizes recent studies on the possible mechanisms of action, potential therapeutic uses, and bioavailability of the nonalcoholic constituents of alcoholic beverages, in particular resveratrol and other polyphenols.

06 May 2014 In Phenolic compounds

Epidemiological and experimental studies have revealed that a mild to moderate drinking of wine, particularly red wine, attenuates the cardiovascular, cerebrovascular, and peripheral vascular risk. However, the experimental basis for such health benefits is not fully understood. The cardioprotective effect of wine has been attributed to both components of wine: the alcoholic portion and, more importantly, the alcohol-free portion containing antioxidants. Wines are manufactured from grapes, which also contain a large variety of antioxidants, including resveratrol, catechin, epicatechin, and proanthocyanidins. Resveratrol is mainly found in the grape skin, whereas proanthocyanidins are found only in the seeds. Recent studies have demonstrated that resveratrol and proanthocyanidin are the major compounds present in grapes and wines responsible for cardioprotection. The purpose of this review is to provide evidence that grapes, wines, and resveratrol are equally important in reducing the risk of morbidity and mortality due to cardiovascular complications. Both wines and grapes can attenuate cardiac diseases such as atherosclerosis and ischemic heart disease. Recently, wine was also found to increase life span by inducing longevity genes. It appears that resveratrol and proanthocyanidins, especially resveratrol, present in grapes and wines play a crucial role in cardioprotective abilities of grapes and wines.

06 May 2014 In Diabetes

Resveratrol is a naturally occurring diphenolic compound exerting numerous beneficial effects in the organism. The present study demonstrated its short-term, direct influence on lipogenesis, lipolysis and the antilipolytic action of insulin in freshly isolated rat adipocytes. In fat cells incubated for 90 min with 125 and 250 microM resveratrol (but not with 62.5 microM resveratrol), basal and insulin-induced lipogenesis from glucose was significantly reduced. The antilipogenic effect was accompanied by a significant diminution of CO(2) release and enhanced production of lactate. The inhibition of glucose conversion to lipids found in the presence of resveratrol was not attenuated by activator of protein kinase C. However, acetate conversion to lipids appeared to be insensitive to resveratrol. In adipocytes incubated for 90 min with epinephrine, 10 and 100 microM resveratrol significantly enhanced lipolysis, especially at lower concentrations of the hormone. However, the lipolytic response to dibutyryl-cAMP, a direct activator of protein kinase A, was unchanged. Further studies demonstrated that, in cells stimulated with epinephrine, 1, 10 and 100 microM resveratrol significantly enhanced glycerol release despite the presence of insulin or H-89, an inhibitor of protein kinase A. The influence of resveratrol on epinephrine-induced lipolysis and on the antilipolytic action of insulin was not abated by the blocking of estrogen receptor and was accompanied by a significant (with the exception of 1 microM resveratrol in experiment with insulin) increase in cAMP in adipocytes. It was also revealed that resveratrol did not change the proportion between glycerol and fatty acids released from adipocytes exposed to epinephrine. Results of the present study revealed that resveratrol reduced glucose conversion to lipids in adipocytes, probably due to disturbed mitochondrial metabolism of the sugar. Moreover, resveratrol increased epinephrine-induced lipolysis. This effect was found also in the presence of insulin and resulted from the synergistic action of resveratrol and epinephrine. The obtained results provided evidence that resveratrol affects lipogenesis and lipolysis in adipocytes contributing to reduced lipid accumulation in these cells.

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