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Life Extension Magazine December 2011

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Mechanisms of action and antiproliferative properties of Brassica oleracea juice in human breast cancer cell lines.

Cruciferous vegetables are an important source of compounds that may be useful for chemoprevention. In this study, we evaluated the antiproliferative activity of juice obtained from leaves of several varieties of Brassica oleracea on both estrogen receptor (ER)-positive (ER+; MCF-7 and BT474) and ER-negative (ER-;MDA-MB-231 and BT20) human breast cancer cell lines. The effect of juice on cell proliferation was evaluated on DNA synthesis and on cell cycle-related proteins. Juice markedly reduced DNA synthesis, evaluated by [3H]thymidine incorporation,starting from low concentrations (final concentration 5-15 mL/L), and this activity was independent of ER. All cauliflower varieties tested suppressed cell proliferation in a dose-dependent manner. Cell growth inhibition was accompanied by significant cell death at the higher juice concentrations, although no evidence of apoptosis was found. Interestingly, the juice displayed a preferential activity against breast cancer cells compared with other mammalian cell lines investigated (ECV304, VERO, Hep2, 3T3, and MCF-10A) (P < 0.01). At the molecular level, the inhibition of proliferation was associated with significantly reduced CDK6 expression and an increased level of p27 in ER+ cells but not in ER- cells, whereas a common feature in all cell lines was significantly decreased retinoblastoma protein phosphorylation. These results suggest that the edible part of Brassica oleracea contains substances that can markedly inhibit the growth of both ER+ and ER- human breast cancer cells, although through different mechanisms. These results suggest that the widely available cruciferous vegetables are potential chemopreventive agents.

J Nutr. 2005 Jun;135(6):1503-9.

Brassica vegetables and cancer prevention. Epidemiology and mechanisms.

This paper first gives an overview of the epidemiological data concerning the cancer-preventive effect of brassica vegetables, including cabbages, kale, broccoli, Brussels sprouts, and cauliflower. A protective effect of brassicas against cancer may be plausible due to their relatively high content of glucosinolates. Certain hydrolysis products of glucosinolates have shown anticarcinogenic properties. The results of six cohort studies and 74 case-control studies on the association between brassica consumption and cancer risk are summarized. The cohort studies showed inverse associations between the consumption of brassica's and risk of lung cancer, stomach cancer, all cancers taken together. Of the case-control studies 64% showed an inverse association between consumption of one or more brassica vegetables and risk of cancer at various sites. Although the measured effects might have been distorted by various types of bias, it is concluded that a high consumption of brassica vegetables is associated with a decreased risk of cancer. This association appears to be most consistent for lung, stomach, colon and rectal cancer, and least consistent for prostatic, endometrial and ovarian cancer. It is not yet possible to resolve whether associations are to be attributed to brassica vegetables per se or tovegetables in general. Further epidemiological research should separate the anticarcinogenic effect of brassica vegetables from the effect of vegetables in general. The mechanisms by which brassica vegetables might decrease the risk of cancer are reviewed in the second part of this paper. Brassicas, including all types of cabbages, broccoli, cauliflower, and Brussels sprouts, may be protective against cancer due to their glucosinolate content. Glucosinolates are usually broken down through hydrolysis catalysed by myrosinase, an enzyme that is released from damaged plant cells. Some of the hydrolysis products, viz. indoles, and isothiocyanates, are able to influence phase 1 and phase 2 biotransformation enzyme activities, thereby possibly influencing several processes related to chemical carcinogenesis, e.g. the metabolism, DNA-binding, and mutagenic activity of promutagens. Most evidence concerning anticarcinogenic effects of glucosinolate hydrolysis products and brassica vegetables has come from studies in animals. In addition, studies carried out in humans using high but still realistic human consumption levels of indoles and brassica vegetables have shown putative positive effects on health. The combination of epidemiological and experimental data provide suggestive evidence for a cancer preventive effect of a high intake of brassica vegetables.

Adv Exp Med Biol. 1999;472:159-68.

Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype.

The role of vegetable consumption in relation to breast cancer risk is controversial. Anticarcinogenic compounds may be present only in specific vegetables, thereby attenuating findings for total vegetable intake. Cruciferous vegetables contain precursors of isothiocyanates (ITCs), which may be chemopreventive through potent inhibition of phase I, and induction of phase II enzymes, such as glutathione S-transferases (GSTs). We investigated associations between consumption of cruciferous vegetables, sources of ITCs, and breast cancer risk, and potential modification of relations by GSTM1 and GSTT1 genotypes. Cases (n = 740) were Caucasian women with incident breast cancer identified from all major hospitals in Erie and Niagara counties. Community controls (n = 810) were frequency matched to cases by age and county. An in-depth interview including a validated FFQ was administered in person. Odds ratios (ORs) and 95% CIs were used to estimate relative risks. Consumption of cruciferous vegetables, particularly broccoli, was marginally inversely associated with breast cancer risk in premenopausal women [4th quartile OR = 0.6, 95% CI (0.40-1.01), P = 0.058]. Associations were weaker or null among postmenopausal women. No significant effects of GST genotype on risk were observed in either menopausal group. These data indicate that cruciferous vegetables may play an important role in decreasing the risk of premenopausal breast cancer.

J Nutr. 2004 May;134(5):1134-8.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Nutr Metab Cardiovasc Dis. 2010 May;20(4):284-94.

The role of virgin olive oil components in the modulation of endothelial function.

The endothelium is involved in many of the processes related to the development of atherosclerosis, which is considered an inflammatory disease. Actually, traditional risk factors for atherosclerosis predispose to endothelial dysfunction, which is manifested as an increase in the expression of specific cytokines and adhesion molecules. There are firm evidence supporting the beneficial effects of olive oil, the most genuine component of the Mediterranean diet. Although the effects of olive oil and other oleic acid-rich dietary oils on atherosclerosis and plasma lipids are well known, the roles of minor components have been less investigated. Minor components constitute only 1-2% of virgin olive oil (VOO) and are composed of hydrocarbons, polyphenols, tocopherols, sterols, triterpenoids and other components usually found in traces. Despite their low concentration, non-fatty acid constituents may be of importance because studies comparing monounsaturated dietary oils have reported different effects on cardiovascular disease. Most of these compounds have demonstrated antioxidant, anti-inflammatory and hypolipidemic properties. In this review, we summarize current knowledge on the effects of these compounds contained in VOO on vascular dysfunction and the mechanisms by which they modulate endothelial activity. Such mechanisms involve the release of nitric oxide, eicosanoids (prostaglandins and leukotrienes) and adhesion molecules, in most cases by activation of nuclear factor kappaB by reactive oxygen species.

J Nutr Biochem. 2006 Jul;17(7):429-45.

Intake of carrots, spinach, and supplements containing vitamin A in relation to risk of breast cancer.

Intake of fruits, vegetables, vitamin A, and related compounds are associated with a decreased risk of breast cancer in some studies, but additional data are needed. To estimate intake of beta-carotene and vitamin A, the authors included nine questions on food and supplement use in a population-based case-control study of breast cancer risk conducted in Maine, Massachusetts, New Hampshire, and Wisconsin in 1988-1991. Multivariate-adjusted models were fit to data for 3,543 cases and 9,406 controls. Eating carrots or spinach more than twice weekly, compared with no intake, was associated with an odds ratio of 0.56 (95% confidence interval 0.34-0.91). Estimated intake of preformed vitamin A from all evaluated foods and supplements showed no trend or monotonic decrease in risk across categories of intake. These data do not allow us to distinguish among several potential explanations for the protective association observed between intake of carrots and spinach and risk of breast cancer. The findings are, however, consistent with a diet rich in these foods having a modest protective effect.

Cancer Epidemiol Biomarkers Prev. 1997 Nov;6(11):887-92.

The protective effects of garlic extract against acetaminophen-induced oxidative stress and glutathione depletion.

Acetaminophen, the most commonly sold over-the-counter antipyretic analgesic, is capable of causing severe and sometimes fatal hepatic damage in humans and experimental animals. The incidence of liver injury due to acetaminophen overdose, either with suicidal intent or by accident, is increasing. Garlic is among those medicinal plants famous for its different health protective effects. In this study, the protective effects of garlic extract on acute acetaminophen-induced liver injury were investigated using freshly isolated rat hepatocytes. The hepatocytes were isolated from Sprague-Dawley male rats by a two step collagenase model. Formation of Reactive Oxygen Species (ROS) and Glutathione (GSH) depletion were studied after addition of acetaminophen to cell suspensions. The effects of garlic extract on prevention of ROS formation as well as GSH depletion was investigated and compared with the effects of N-Acetyl Cysteine (NAC) as the standard treatment. Reactive oxygen species formation was assessed by a spectrofluorometry method and garlic extract was shown to be as effective as NAC in decreasing ROS formation induced by acetaminophen. Glutathione (GSH) levels of hepatocytes were determined using HPLC. Garlic extract was effective in preventing GSH depletion significantly (p < 0.05). It is concluded that garlic extract has an antioxidant effect and can protect hepatocytes from GSH depletion following NAPQI production.

Pak J Biol Sci. 2009 May 15;12(10):765-71.

The aqueous extract of Asparagus officinalis L. by-product exerts hypoglycaemic activity in streptozotocin-induced diabetic rats.

BACKGROUND: The inedible bottom part of asparagus (Asparagus officinalis L.) spears, around one-third to one-half of the total length, is always discarded as by-product. Since it still contains various bioactive substances, this by-product might have potential usage in food supplements for its therapeutic effects. In this study the hypoglycaemic effect of the aqueous extract of asparagus by-product (AEA) was evaluated in a streptozotocin (STZ)-induced diabetic rat model. RESULTS: Continuous administration of AEA for 21 days significantly decreased fasting serum glucose and triglyceride levels but markedly increased body weight and hepatic glycogen level in diabetic rats. In an oral glucose tolerance test, both the blood glucose level measured at 30, 60 and 120 min after glucose loading and the area under the glucose curve showed a significant decrease after AEA treatment. CONCLUSION: The results of this study demonstrate that AEA has hypoglycaemic and hypotriglyceridaemic functions, suggesting that it might be useful in preventing diabetic complications associated with hyperglycaemia and hyperlipidaemia.

J Sci Food Agric. 2011 Aug 30;91(11):2095-9.

The effects of essential oils and aqueous tea infusions of oregano (Origanum vulgare L. spp. hirtum), thyme (Thymus vulgaris L.) and wild thyme (Thymus serpyllum L.) on the copper-induced oxidation of human low-density lipoproteins.

In this study, the antioxidative capacity effect of essential oils and aqueous tea infusions obtained from oregano, thyme and wild thyme on the oxidation susceptibility of low-density lipoproteins (LDL) has been studied. The results indicate a dose-dependent protective effect of the tested essential oils and aqueous tea infusions on the copper-induced LDL oxidation. The protective effect of essential oils is assigned to the presence of phenolic monoterpenes, thymol and carvacrol, which are identified as the dominant compounds in these essential oils. The strong protective effect of aqueous tea infusions is proposed to be the consequence of large amounts of polyphenols, namely rosmarinic acid and flavonoids (quercetin, eriocitrin, luteolin-7-O-glucoside, apigenin-7-O-glucoside, luteolin, apigenin), with the most pronounced effect in the case of oregano. These findings may have implications for the effect of these compounds on LDL in vivo.

Int J Food Sci Nutr. 2007 Mar;58(2):87-93.

Indole-3-carbinol and 3,3'-diindolylmethane induce apoptosis in human prostate cancer cells.

Cruciferous vegetables contain glucobrassicin which, during metabolism, yields indole-3-carbinol (I3C). In a low pH environment I3C is converted into polymeric products, among which 3,3'-diindolylmethane (DIM) is the main one. The apoptotic effects of I3C and DIM were exhibited in human breast cancer cells. The objectives of this study were: (a) examination of the potential effects of I3C and DIM on the proliferation and induction of apoptosis in human prostate cancer cell lines with different p53 status; (b) to try to characterise the mechanism(s) involved in these effects. Our results indicate that both indole derivatives suppress the growth of these cells in a dose- and time-dependent manner, by inducing apoptosis. It appears that these indolic compounds may offer effective means against prostate cancer. Induction of apoptosis was p53-independent. Moreover, the indole derivatives employed did not affect the levels of bcl-2, bax and fasL.

Food Chem Toxicol. 2003 Jun;41(6):745-52.