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Biomedical subjects

J A Milner

Publications and source records attributed to J A Milner.

At least 19 recordsLinked to original sources
PubMed2001

Mechanisms by which garlic and allyl sulfur compounds suppress carcinogen bioactivation. Garlic and carcinogenesis.

Overall, a host of studies provides compelling evidence that garlic and its organic allyl sulfur components are effective inhibitors of the cancer process. These studies reveal that the benefits of garlic are not limited to a specific species, to a particular tissue, or to a specific carcinogen. Several mechanisms are likely to account for this protection. Notable among these is a depression in nitrosamine formation and a reduction in carcinogen bioactivation. The benefits provided by garlic must be viewed as part of the entire diet, since several dietary constituents can influence the degree of protection. More than one compound is responsible for the anticancer properties associated with garlic. Future research should focus on how genetic variability and daily environmental factors influence the anticancer benefits attributed to garlic and its allyl sulfur components.

Allyl Compounds↗
PubMed2001

Diet and cancer prevention.

Research from several sources provides strong evidence that vegetables, fruits, and whole grains, dietary fibre, certain micronutrients, some fatty acids and physical activity protect against some cancers. In contrast, other factors, such as obesity, alcohol, some fatty acids and food preparation methods may increase risks. Unravelling the multitude of plausible mechanisms for the effects of dietary factors on cancer risk will likely necessitate that nutrition research moves beyond traditional epidemiological and metabolic studies. Nutritional sciences must build on recent advances in molecular biology and genetics to move the discipline from being largely 'observational' to focusing on 'cause and effect'. Such basic research is fundamental to cancer prevention strategies that incorporate effective dietary interventions for target populations.

Alcohol Drinking↗
PubMed2001

A historical perspective on garlic and cancer.

Epidemiological and laboratory studies provide insight into the anticarcinogenic potential of garlic and its constituent compounds. Both water- and lipid-soluble allyl sulfur compounds are effective in blocking a myriad of chemically induced tumors. Part of the protection from these compounds probably relates to a block in nitrosamine formation and metabolism. However, blockage in the initiation and promotion phases of the carcinogenicity of various compounds, including polycyclic hydrocarbons, provide evidence that garlic and its constituents can alter several phase I and II enzymes. Their ability to block experimentally induced tumors in a variety of sites including skin, mammary and colon, suggests a general mechanism of action. Changes in DNA repair and in immunocompetence may also account for some of this protection. Some, but not all, allyl sulfur compounds can also effectively retard tumor proliferation and induce apoptosis. Changes in cellular thiol and phosphorylation stains may account for some of these antitumorigenic properties. The anticarcinogenic potential of garlic can be influenced by several dietary components including specific fatty acids, selenium, and vitamin A. Since garlic and its constituents can suppress carcinogen formation, carcinogen bioactivation, and tumor proliferation it is imperative that biomarkers be established to identify which individuals might benefit most and what intakes can occur with ill consequences.

Allyl Compounds↗
PubMed2001

The influence of heating on the anticancer properties of garlic.

Allyl sulfur compounds are the major active constituents found in crushed garlic. Research has revealed that garlic and its lipid- or water-soluble components have many pharmacologic properties; however, studies also demonstrate that heating has a negative influence on these beneficial effects. We recently conducted several studies to investigate the influence of microwave or oven heating on the anticarcinogenesis property of garlic. Our studies showed that as little as 60 s of microwave heating or 45 min of oven heating can block garlic's ability to inhibit in vivo binding of mammary carcinogen [7,12-dimethylbenzene(a)anthracene (DMBA)] metabolites to rat mammary epithelial cell DNA. Allowing crushed garlic to "stand" for 10 min before microwave heating for 60 s prevented the total loss of anticarcinogenic activity. Our studies demonstrated that this blocking of the ability of garlic was consistent with inactivation of alliinase. These studies suggest that heating destroyed garlic's active allyl sulfur compound formation, which may relate to its anticancer properties.

Animals↗
PubMed2001

Possible mechanism by which allyl sulfides suppress neoplastic cell proliferation.

Both oil- and water-soluble allyl sulfur compounds from garlic have been found to possess antitumorigenic properties. These antitumorigenic properties increase as exposure increases both in vitro and in vivo. Generally, oil-soluble allyl sulfur compounds are more effective antiproliferative agents than their water-soluble counterparts. The ability of these compounds to suppress proliferation is associated with a depression in cell cycle progression and the induction of apoptosis. This depression in cell division coincides with an increase in the percentage of cells blocked in the G(2)/M phase of the cell cycle. A depression in p34(cdc2) kinase may account for this blockage in cell division.

Allyl Compounds↗
PubMed2000

Functional foods: the US perspective.

Widespread interest in the possibility that selected foods might promote health has resulted in the coining of the term functional food, although agreement about what is and what is not a functional food is lacking. Public interest in functional foods is increasing because of higher health care costs; the passage of federal legislation affecting many food categories, including the expanded category of dietary supplements; and recent scientific discoveries linking dietary habits with the development of many diseases, including coronary heart disease and some cancers. A variety of foods have been proposed as providing health benefits by altering one or more physiologic processes. Biomarkers are needed to assess the ability of functional foods or their bioactive components to modify disease and to evaluate the ability of these foods to promote health, growth, and well-being. Evidence suggests that several biomarkers may be useful for distinguishing between diseased and nondiseased states and even for predicting future susceptibility to disease. A variety of biomarkers will probably be needed to develop a profile for an individual that reflects the impact of diet on performance and health. Another area of interest is the interaction of nutrients and their association with genetics. These interactions may account for the inconsistent interrelations observed between specific dietary constituents and the incidence of disease. Greater understanding of how diet influences a person's genetic potential, overall performance, and susceptibility to disease can have enormous implications for society. As new discoveries are made in this area, consumers will need access to this information so that they can make informed decisions.

Biological Availability↗
PubMed2000

Summary

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Journal Article↗
PubMed2000

Creating a new paradigm in nutrition research within the National Cancer Institute.

Almost two decades after Doll and Peto (1981) provided evidence that one third of cancer deaths are related to diet, it remains unclear which dietary components may be key in cancer prevention. Although the complexity of the diet can become overwhelming, the National Cancer Institute (NCI) of the National Institutes of Health (NIH) has remained steadfast in its commitment to defining the roles that diet and nutrition have in the development of cancer and has provided increased research and training support to assist in unraveling this interrelationship. Evidence for this sustained commitment is highlighted by a fourfold increase in NCI expenditures for nutrition research and training from 1983 to 1998; this substantial increase reflects a trend that is occurring in some universities and the private sector. More than one third of the nutrition-related NCI research is funded by the Division of Cancer Prevention. Supported investigations cover the gamut from basic mechanisms of action of dietary constituents, methodology development, human metabolic studies, clinical trials of dietary modification and the chemopreventive potential of individual nutrients to population-based studies.

Antioxidants↗
PubMed2000

Flavonoids suppress androgen-independent human prostate tumor proliferation.

The present studies compared the effects of selected bioflavonoids on the proliferation of androgen-independent human prostatic tumor cells (PC-3). Complete growth retardation was observed in PC-3 cells treated with 100 microM quercetin, kaempferol, and luteolin, while isomolar genistein, apigenin, and myricetin suppressed PC-3 proliferation by 73%, 70%, and 59%, respectively (p < 0.05). Naringenin and rutin were not as effective and inhibited growth by < 25%. Exposure to increasing concentrations of quercetin and kaempferol led to a dose-dependent decrease in proliferation. Refeeding kaempferol-treated cells (50 microM) complete medium without the flavonoid resulted in a return toward control growth rates. Similar growth recovery was not observed in quercetin-treated cells. The antiproliferative response of PC-3 cells to quercetin and kaempferol was additive when supplemented to the medium at 25 microM. A block in G2-to-M phase progression was observed after the addition of 25 microM kaempferol. When quercetin reached 100 microM, an increase in the proportion of cells in the S phase became apparent within 24 hours. Apoptosis was not evident, even when concentrations of quercetin or kaempferol were raised to 100 microM. The present studies suggest that alterations in cell cycle progression contribute significantly to the antiproliferative effects of quercetin and kaempferol in PC-3 cells.

Androgens↗
PubMed2000

Allyl sulfides modify cell growth.

Extensive evidence points to the ability of allyl sulfides from garlic to suppress tumor proliferation both in vitro and in vivo. This antineoplastic effect is generally greater for lipid-soluble than water-soluble allyl sulfides. Both concentration and duration of exposure can increase the antiproliferative effects of lipid- and water-soluble allyl sulfides. Part of their antiproliferative effects may relate to an increase in membrane fluidity and a suppression of integrin glycoprotein IIb-IIIa mediated adhesion. Alterations in cholesterol, arachidonic acid, phospholipids and/or thiols may account for these changes in membrane function. Allyl sulfides are also recognized for their ability to suppress cellular proliferation by blocking cells in the G2/M phase and by the induction of apoptosis. This increase in the G2/M and apoptotic cell populations correlates with depressed p34cdc2 kinase activity, increased histone acetylation, increased intracellular calcium and elevated cellular peroxide production. While impressive pre-clinical data exist about the antineoplastic effects of allyl sulfur compounds, considerably more attention needs to be given to their effects in humans. The composition of the entire diet and a host of genetic/epigenetic factors will likely determine the true benefits that might arise from allyl sulfur compounds from garlic and other Allium foods.

Allyl Compounds↗
PubMed2000

Diallyl disulfide inhibits p34(cdc2) kinase activity through changes in complex formation and phosphorylation.

Previous studies from our laboratory demonstrated that diallyl disulfide (DADS), an oil-soluble allyl sulfur compound found in processed garlic, markedly suppressed p34(cdc2) kinase activity and induced a G(2)/M phase arrest in cultured human colon tumor (HCT-15) cells. The present studies reveal that suppression of p34(cdc2) kinase activity by DADS does not result from direct interactions with the protein, but through changes in factors influencing the formation and conversion of the enzyme to its active form. Flow cytometric analyses showed that the increased proportion of cells in the G(2)/M phase following DADS treatment was accompanied by an increase in cyclin B(1) protein expression. A temporal and dose-dependent response in cyclin B(1) expression was observed in cells treated with DADS. Western blot analysis revealed that 50 microM DADS did not influence the quantity of p34(cdc2) protein expressed, but did decrease the amount associated with cyclin B(1) by 26% (P < 0.05). Exposure of unsynchronized cells to 25 or 50 microM DADS caused a trend towards increased p34(cdc2) hyperphosphorylation (17 and 22%, respectively). Exposure of synchronized cells to 100 microM DADS increased p34(cdc2) hyperphosphorylation by 15% (P < 0.05). Consistent with its ability to slightly increase the quantity of hyperphosphorylated p34(cdc2), DADS, 25 or 50 microM, decreased cdc25C protein expression by 23 and 46%, respectively (P < 0.05). The present studies suggest that the ability of DADS to inhibit p34(cdc2) kinase activation occurs because of decreased p34(cdc2)/cyclin B(1) complex formation and modest p34(cdc2) hyperphosphorylation.

Allyl Compounds↗
PubMed1999

Selenium-enriched Agaricus bisporus mushrooms suppress 7,12-dimethlybenz[a]anthracene bioactivation in mammary tissue.

The present studies compared dietary Se (1.0 microg/g) when provided as either fortified Agaricus bisporus mushrooms, or sodium selenite on the in vivo metabolism of 7,12-dimethylbenz(a)anthracene (DMBA). Dietary addition of Se unenriched A. bisporus mushrooms at 2% did not alter the occurrence of DMBA induced DNA adducts or the activity of glutathione S-transferase (GST). However, the addition of Se as enriched mushrooms, or as selenite, significantly increased both liver and mammary GST activity. Providing sodium selenite, or enriched mushrooms also significantly reduced total and anti-3,4-dihydrodiol-1,2-epoxide-deoxyguanosine adducts compared to feeding the basal diet (P < 0.05). These investigations provide evidence that Se enriched mushrooms can be used as an effective method to retard chemically induced tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Heating garlic inhibits its ability to suppress 7, 12-dimethylbenz(a)anthracene-induced DNA adduct formation in rat mammary tissue.

The present studies compared the impact of heating, either by microwave or convection oven, on the ability of garlic to reduce the in vivo bioactivation of 7,12-dimethylbenz(a)anthracene (DMBA) in 55-d-old female Sprague-Dawley rats. In study 1, rats were fed a semipurified casein-based diet and treated by gastric gavage thrice weekly for 2-wk with crushed garlic (0.7 g in 2 mL corn oil) or the carrier prior to DMBA treatment (50 mg/kg body weight). Providing crushed garlic reduced by 64% (P < 0.05) the quantity DMBA-induced DNA adducts present in mammary epithelial cells compared to controls. In study 2, microwave treatment for 60 s, but not 30 s, decreased (P < 0.05) the protection provided by garlic against DMBA-induced adduct formation. In study 3, allowing crushed garlic to stand for 10 min prior to microwave heating for 60 s significantly (P < 0.05) restored its anticarcinogenic activity. Microwave heating of garlic for 30 s resulted in a 90% loss of alliinase activity. Heating in a convection oven (study 4) also completely blocked the ability of uncrushed garlic to retard DMBA bioactivation. Study 5 revealed that providing either 0.105 micromol diallyl disulfide or S-allyl cysteine by gastric gavage thrice weekly for 2 wk was effective in retarding DMBA bioactivation but isomolar alliin was not. These studies provide evidence that alliinase may be important for the formation of allyl sulfur compounds that contribute to a depression in DMBA metabolism and bioactivation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Functional foods and health promotion.

Statements about the ability of selected foods to reduce the risk of diseases and to enhance the quality of life continue to captivate, and at times polarize, opinions. Interests in these "functional" foods and their active components are being propelled by increasing health care cost, recent legislative events and mounting scientific evidence. Increasingly, scientists are being asked to clarify the precise role that foods have in maintaining and promoting health. Accepting this movement as an opportunity to "optimize nutrition" rather than as a way in which to endorse good or bad foods or as a marketing gimmick will surely make it more acceptable to many scientists. However, the response to functional foods depends on several factors, including genetics, physiologic state and the composition of the entire diet. Although evaluation of the benefits or risks of foods normally does not entail the same extensive examination as that required of drugs, this does not negate the need for sound scientific information for making recommendations to the consumer. Identification of sensitive and reliable biomarkers will be key to adequate assessment of the true effect of foods and their components. Inulin and oligofructose are components of the diet that deserve added attention for their potential health benefits. Evidence that oligofructose and inulin alter several biomarkers, including gastrointestinal transit time, experimentally induced neoplasia and colonic microflora, suggests that these nondigestible carbohydrates are naturally occurring dietary constituents that may improve the quality of life and increase disease resistance in both humans and animals.

Animals↗
PubMed1998

Depressed p34cdc2 kinase activity and G2/M phase arrest induced by diallyl disulfide in HCT-15 cells.

The present studies reveal the antiproliferative property of diallyl disulfide (DADS) in cultured human colon tumor cells (HCT-15) relative to its ability to decrease the proportion of cells in the G1 phase and increase the proportion of cells in the G2/M phase. The shift in the proportion of cells blocked in the G2/M phase increased as the concentration and duration of DADS exposure increased. Refeeding DADS-treated cells (50 microM) with complete medium without DADS resulted in a return to normal proliferation rates. Consistent with the G2/M phase arrest, DADS exposure inhibited p34cdc2 kinase activity within four hours of treatment. The maximum depression in p34cdc2 kinase activity (53%) occurred when 25 microM DADS was added to the medium. The present studies suggest that depressed p34cdc2 kinase activity is likely one of the early cellular events that may account for the antiproliferative property of DADS.

Allyl Compounds↗
PubMed1998

No effects of low copper intake on rat mammary tissue superoxide dismutase 1 activity and mammary chemical carcinogenesis.

Variations in copper-containing superoxide dismutase (SOD) 1 are hypothesized to produce variations in resistance to carcinogenesis, particularly in mammary tissue. Therefore, it is reasonable to speculate that low copper intake, which causes low SOD 1 activities in various tissues, would cause poor resistance to mammary carcinogenesis. This idea was tested using female rats fed diets either low or adequate in copper (< 0.5 or 8 mg copper/kg diet) plus or minus oral gavage with the mammary carcinogen 7,12-dimethylbenz[a]anthracene (5 mg/kg, given 5 wk after dietary modification, 28 wk before sacrifice). Low copper intake produced low activities of two serum copper enzymes: ceruloplasmin and extracellular SOD. In contrast, low copper intake did not affect mammary tissue SOD 1 activities, nor did it statistically influence any of several parameters of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗