Search PubMed⌕ Search

Biomedical subjects

K K Carroll

Publications and source records attributed to K K Carroll.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inhibition of human breast cancer cell proliferation and delay of mammary tumorigenesis by flavonoids and citrus juices.

Two citrus flavonoids, hesperetin and naringenin, found in oranges and grapefruit, respectively, and four noncitrus flavonoids, baicalein, galangin, genistein, and quercetin, were tested singly and in one-to-one combinations for their effects on proliferation and growth of a human breast carcinoma cell line, MDA-MB-435. The concentration at which cell proliferation was inhibited by 50% (IC50), based on incorporation of [3H]thymidine, varied from 5.9 to 140 micrograms/ml for the single flavonoids, with the most potent being baicalein. IC50 values for the one-to-one combinations ranged from 4.7 micrograms/ml (quercetin + hesperetin, quercetin + naringenin) to 22.5 micrograms/ml (naringenin + hesperetin). All the flavonoids showed low cytotoxicity (> 500 micrograms/ml for 50% cell death). Naringenin is present in grapefruit mainly as its glycosylated form, naringin. These compounds, as well as grapefruit and orange juice concentrates, were tested for their ability to inhibit development of mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats. Two experiments were conducted in which groups of 21 rats were fed a semipurified diet containing 5% corn oil and were given a 5-mg dose of DMBA intragastrically at approximately 50 days of age while in diestrus. One week later, individual groups were given double-strength grapefruit juice or orange juice or fed naringin or naringenin at levels comparable to that provided by the grapefruit juice; in the second experiment, the rats were fed a semipurified diet containing 20% corn oil at that time. As expected, rats fed the high-fat diet developed more tumors than rats fed the low-fat diet, but in both experiments tumor development was delayed in the groups given orange juice or fed the naringin-supplemented diet compared with the other three groups. Although tumor incidence and tumor burden (grams of tumor/rat) were somewhat variable in the different groups, rats given orange juice had a smaller tumor burden than controls, although they grew better than any of the other groups. These experiments provide evidence of anticancer properties of orange juice and indicate that citrus flavonoids are effective inhibitors of human breast cancer cell proliferation in vitro, especially when paired with quercetin, which is widely distributed in other foods.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Effect of tocotrienols on the growth of a human breast cancer cell line in culture.

The tocotrienol-rich fraction (TRF) of palm oil consists of tocotrienols and some alpha-tocopherol (alpha-T). Tocotrienols are a form of vitamin E having an unsaturated side-chain, rather than the saturated side-chain of the more common tocopherols. Because palm oil has been shown not to promote chemically-induced mammary carcinogenesis, we tested effects of TRF and alpha-T on the proliferation, growth, and plating efficiency (PE) of the MDA-MB-435 estrogen-receptor-negative human breast cancer cells. TRF inhibited the proliferation of these cells with a concentration required to inhibit cell proliferation by 50% of 180 microgram/mL whereas alpha-T had no effect at concentrations up to 1000 microgram/mL as measured by incorporation of [3H]thymidine. The effects of TRF and alpha-T also were tested in longer-term growth experiments, using concentrations of 180 and 500 microgram/mL. We found that TRF inhibited the growth of these cells by 50%, whereas alpha-T did not. Their effect on the ability of these cells to form colonies also was studied, and it was found that TRF inhibited PE, whereas alpha T had no effect. These results suggest that the inhibition is due to the presence of tocotrienols in TRF rather than alpha T.

Antioxidants↗
PubMed1995

Soy consumption and cholesterol reduction: review of animal and human studies.

Animal proteins such as casein are more hypercholesterolemic than soy protein or other plant proteins when fed to rabbits in low-fat, cholesterol-free, semipurified diets. A casein-amino acid mixture produces a hypercholesterolemia similar to that of casein. This appears to be mainly due to lysine and methionine, although other essential amino acids probably contribute to the effect. Arginine appeared to counteract the hypercholesterolemic effects of other essential amino acids. Soy protein gave a lower level of serum cholesterol in rabbits than did a soy protein-amino acid mixture, suggesting the presence of factors in soy protein that counteract the effects of hypercholesterolemic amino acids. Soy protein is also less hypercholesterolemic than casein in other animal species, particularly when the diet contains cholesterol, and substitution of soy protein for animal protein in the diet reduces the concentration of serum cholesterol in humans. This effect is somewhat variable but is generally greater in hypercholesterolemic than in normocholesterolemic subjects. The differing effects of dietary proteins on serum cholesterol concentrations in humans and in rabbits are primarily due to changes in LDL cholesterol, and the hypercholesterolemia produced by dietary casein is associated with down-regulation of hepatic LDL receptors.

Amino Acids↗
PubMed1994

Effects of long-chain fatty amines on the growth of ras-transformed NIH 3T3 cells.

A number of aliphatic primary amines were tested for their effects on the growth of ras-transformed NIH 3T3 cells (PAP2 cells), as measured by incorporation of tritiated thymidine into DNA. Long-chain, saturated amines (C12 to C18) were growth inhibitory, whereas short-chain amines (C6, C8) were not. Farnesylamine, a branched-chain, unsaturated amine (C15), had an IC50 of 6.9 microM compared to IC50 values of 13.1 to 45.8 microM for straight-chain, saturated amines. Oleylamine, with an IC50 of 0.1 microM, was the most potent inhibitor. The long-chain amines, but not the short-chain amines, were also effective inhibitors of protein kinase C, assayed in vitro in a cell-free system. In addition, studies with indo-1-loaded PAP2 cells showed that long-chain amines induced a reversible rise in intracellular free Ca2+ concentration. Growth inhibition by the amines was positively correlated with this effect, suggesting that factors other than protein kinase C may be involved in the inhibition of growth of PAP2 cells by long-chain amines.

3T3 Cells↗
PubMed1994

Early lesion development in the aortas of rabbits fed low-fat, cholesterol-free, semipurified casein diet.

The initial endothelial morphological alterations and the development of raised, lipid-containing lesions in rabbit aortas were examined after 1 and 3 months on a casein-enriched, semipurified, cholesterol-free diet. The alterations were compared with those in rabbits fed soy-protein in the place of casein and with age-matched, chow-fed, control animals. Using immunohistochemistry macrophages, T-lymphocytes, and smooth muscle cells were identified in the lesions, and an expression of leukocyte adhesion molecules, VCAM-1, ICAM-1 and, occasionally, E-selectin was seen in sections of the aortas of casein-fed rabbits. The initial alterations in the endothelium appear to include evidence of endothelial injury and white blood cell adhesion. No evidence of extracellular liposome formation was observed. This model of atherogenesis is consistent with endothelial injury being an important component of diet-induced atherogenesis and has similarities to human atherosclerosis.

Animals↗
PubMed1994

Hypercholesterolemic responses in rabbits to selected groups of dietary essential amino acids.

In rabbits, elevation of LDL cholesterol is produced by feeding a cholesterol-free, semipurified diet containing 30% casein amino acid mixture, but not by feeding the same diet containing 14.7% of the casein amino acid mixture, corresponding to a normal level of dietary protein. The hypercholesterolemic response was greater when all essential amino acids except arginine or all ketogenic essential amino acids (lysine, leucine, isoleucine, threonine, phenylalanine, tryptophan and glycine) were selectively fed at three times the normal level. In the present experiments, the same high levels of lysine, leucine and methionine produced a substantial hypercholesterolemia, addition of either isoleucine + threonine or isoleucine + valine did not enhance the effect, and a mixture of threonine, histidine, phenylalanine, tryptophan and glycine gave only a moderate response. A combination of lysine and methionine produced a greater effect than either lysine and leucine or leucine and methionine. Hypercholesterolemic diets containing high levels of lysine and leucine did not cause significantly greater plasma ketone bodies or free fatty acids. Differences in growth rates and ketogenic responses were not generally correlated with hypercholesterolemia.

Amino Acids, Essential↗
PubMed1993

Farnesylamine: an inhibitor of farnesylation and growth of ras-transformed cells.

Farnesylamine, an analogue of farnesol, was shown to inhibit growth of PAP2 cells (ras-transformed NIH 3T3 cells) in a dose-dependent manner. This inhibition was overcome by adding farnesol to the culture medium, but not by adding geranylgeraniol, squalene, cholesterol, dolichol, myristic acid or palmitic acid. Farnesylamine inhibited both farnesyl/protein transferase and geranylgeranyl/protein transferase in whole cell extracts and also inhibited the prenylation of proteins, particularly ras p21, in PAP2 cells. Inhibition of prenylation was associated with increased biosynthesis of other products of the mevalonate biosynthetic pathway. These observations suggest that inhibition of the growth of PAP2 cells by farnesylamine may be due to blocking of ras-mediated signal transduction. This offers a means of investigating mechanisms involved in ras action and raises the possibility of developing novel strategies for anticancer therapy.

3T3 Cells↗
PubMed1992

Effect of high levels of selected dietary essential amino acids on hypercholesterolemia and down-regulation of hepatic LDL receptors in rabbits.

Earlier studies showed that the elevation of serum total and low density lipoprotein (LDL) cholesterol levels produced in rabbits by feeding high levels of a casein amino acid mixture in a cholesterol-free, semipurified diet was due primarily to the essential amino acids (EAA) in the mixture. Replacing all of the non-essential amino acids in the mixture by glutamic acid (45% EAA+Glu) had little effect on the hypercholesterolemia produced by the EAA. Experiments designed to identify the hypercholesterolemic EAA showed that (i) feeding high levels of ketogenic EAA only (45% EketoAA) gave a substantial but variable elevation of serum total and LDL cholesterol and (ii) feeding high levels of all EAA except arginine (45% EAA-Arg) gave a particularly strong hypercholesterolemic response. In rabbits fed the 45% EAA-Arg diet and to a lesser extent, in those fed the 45% EAA+Glu diet, EDTA-sensitive binding of 125I-LDL to hepatic membranes in vitro was reduced compared to a control, low-cholesterolemic group fed all essential and non-essential amino acids at a level corresponding to 14.7% casein, indicating that the hypercholesterolemia was associated with down-regulation of hepatic LDL receptors.

Amino Acids, Essential↗
PubMed1992

Dietary fat and breast cancer.

High-fat diets are thought to increase the risk of breast cancer because animals develop mammary cancer more readily when they are fed high-fat compared to low-fat diets, and breast cancer incidence and mortality are higher in countries with high-fat as compared to those with low-fat diets. Prospective cohort studies and case-control studies have failed to provide much support for this theory, but such studies are less capable of showing the relationship because of smaller differences in dietary fat intakes of the study populations; difficulties in assessing the diets of individuals over a period of time; and possible differences in genetic susceptibility of cases and controls to breast cancer. Studies on migrants have shown that breast cancer incidence and mortality increase in populations who move from countries with low-fat to those with high-fat diets, indicating that observed geographical differences in breast cancer are due to environmental rather than genetic factors. This is supported by time-trend studies showing that breast cancer increases in countries as the level of fat in the diet rises. Controlled, long-term dietary trials are needed to determine whether the converse is true: namely, that reduction of dietary fat can reduce the risk of breast cancer. Large groups are required to achieve statistical significance, but smaller numbers may be adequate for studies on high-risk individuals. Preliminary experiments already have demonstrated the feasibility of carrying out such dietary trials.

Animals↗
PubMed1992

Effects of a long-chain fatty amine on mammary carcinogenesis induced in female Sprague-Dawley rats by DMBA.

Reports that protein kinase C is inhibited by sphingosine and other long-chain amines and the suggestion that promotion of mammary carcinogenesis by dietary fat is mediated by protein kinase C prompted us to investigate the effects of a long-chain amine, 1-octadecylamine, on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene in rats fed a high-fat diet. Rats fed the amine sulfate at a level of 0.01% in a semipurified diet containing 20% corn oil developed more tumors than those fed the high-fat diet alone, although body weight gain was inhibited slightly. Rats fed the amine sulfate at 0.1% of the diet developed very few tumors compared with those fed either the high-fat diet or a low-fat diet containing 5% corn oil. At the higher level, the C18 amine also caused a marked inhibition of body weight gain.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Dolichol: function, metabolism, and accumulation in human tissues.

Dolichol, a homologous series of alpha-saturated polyisoprenoid alcohols containing 14-24 isoprene units, was first isolated and characterized about 30 years ago. The phosphorylated form, dolichyl phosphate, is required for the biosynthesis of biologically important N-linked glycoproteins. Dolichol itself is synthesized by a common isoprenoid pathway from acetate and synthesis can be inhibited by some of the factors that inhibit cholesterol biosynthesis. It is metabolized very slowly and accumulates in tissues during aging and in certain lipid storage diseases. Dolichyl phosphate and cholesterol also accumulate in tissues during aging, but to a lesser extent than dolichol. Although dolichol and cholesterol have important metabolic functions, their accumulation in tissues can have deleterious effects.

Adult↗
PubMed1992

Dolichol and polyprenol kinase activities in microsomes from etiolated rye seedlings.

Dolichol kinase activity in microsomes from etiolated rye seedlings had a pH optimum at 8 with a shoulder at pH 6.5. Triton X-100 (0.4%) was required for optimum activity. Exogenous divalent cations did not enhance activity, although Mg+2 was added routinely. Rye microsomes were found to contain dolichol and polyprenol in a ratio of 3 to 2. Rye, soybean embryo, and rat liver microsomes catalyzed the synthesis of 78, 52, and 516 nmol [14C]dolichyl phosphate/(mg microsomal protein.h) compared with 21, 22, and 49 nmol [3H]polyprenyl phosphate/(mg microsomal protein.h), respectively. It is clear that microsomes from plant systems can catalyze the phosphorylation of polyprenol better than rat liver when compared with their abilities to catalyze the phosphorylation of dolichol. It is not known whether one or more kinases is responsible for catalyzing the phosphorylation of these two closely related groups of compounds.

Animals↗
PubMed1991

A proposed mechanism for effects of diet on mammary cancer.

Growth and development of mammary glandular parenchyma appear to be strongly influenced by the associated adipose tissue. Because fat is the major form of energy storage in the body, any changes in energy balance will be reflected in the weight of adipose tissue to a greater extent than in body weight as a whole. High-fat diets tend to encourage energy storage and may promote mammary cancer by increasing the amount of adipose tissue in the gland. The intimate association of adipose and glandular tissue would facilitate the transfer of any growth-promoting substances, such as polyunsaturated fatty acids, eicosanoids, estrogens, or other growth factors, from the adipose to the glandular tissue. Conversely, low-fat diets or restriction of food intake may decrease the risk of mammary cancer by reducing the amount of adipose tissue and thus reducing exposure of the glandular tissue to such growth-promoting substances.

Adipose Tissue↗
PubMed1991

Dietary fats and cancer.

Evidence relating dietary fat to cancer at sites such as the breast and colon is provided by experiments showing that animals fed high-fat diets develop cancer at these sites more readily than do animals fed low-fat diets and by epidemiological data from different countries showing strong positive correlations between cancer incidence and mortality, and level of dietary fat. Experiments on animals have indicated that polyunsaturated vegetable oils promote cancer more effectively than do saturated fats or polyunsaturated fish oils, whereas in the epidemiological data, total dietary fat correlates with cancer incidence and mortality at least as well as does any particular type of fat. Case-control and cohort studies have not shown strong indications of a relationship between dietary fat and cancer, perhaps because of methodological difficulties inherent in such studies. The weight of evidence continues to indicate that long-term adherence to a low-fat diet can reduce the risk of some common types of cancer.

Animals↗
PubMed1991

Calcium and carcinogenesis of the mammary gland.

Effects of dietary calcium on mammary carcinogenesis in rats were investigated because of evidence that calcium counteracts the promotion of colon cancer by dietary fat and because experimental diets for rats normally contain higher amounts of calcium and vitamin D than do human diets. Our earlier experiments indicated that yields of tumors induced in young, Sprague-Dawley rats by 7,12-dimethylbenz(a)-anthracene (DMBA) were higher when dietary calcium, phosphate, and vitamin D were decreased. Results of an experiment in which dietary amounts of calcium, phosphate, and vitamin D were varied independently suggested that phosphate and vitamin D have interactive effects with calcium. Another experiment in which dietary vitamin D alone was varied provided evidence that higher amounts inhibited tumorigenesis in the presence of low amounts of calcium and phosphate but the results with a high-calcium and -phosphate diet were inconclusive. The findings suggest that low amounts of dietary calcium and vitamin D and high amounts of phosphate increase susceptibility to DMBA-induced mammary neoplasia.

Animals↗
PubMed1991

Review of clinical studies on cholesterol-lowering response to soy protein.

Experiments on animals have shown that soybean protein has hypocholesterolemic and antiatherogenic properties. In human beings, substitution of soy protein for dietary animal protein or addition of soy protein to the diet lowers total and low-density-lipoprotein cholesterol levels in individuals with hypercholesterolemia. Reductions of 20% or more have been obtained with diets high in protein (about 20% of total energy) and relatively low in fat. Triglycerides are also decreased, particularly in subjects with hypertriglyceridemia, but soy-protein diets appear to have little effect on high-density-lipoprotein cholesterol levels. Responses are similar in men and women, but may be greater in younger than in older subjects. The hypocholesterolemic effect is thought to be mainly attributable to the protein itself rather than to nonprotein components of soy-protein preparations. The mechanism of action is not known, and it may not be possible to explain the observed effects in human beings and in experimental animal models by the same mechanism. Although the hypocholesterolemic response to dietary soy protein has been observed by a number of European research groups, substitution of soy protein for animal protein in North American diets has generally had little effect, for reasons that are still not clear.

Animals↗