Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.108 (lactase)
 2,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of brush border membrane-associated hydrolases such as alkaline phosphatase (Alkpase), aminopeptidase, dipeptidyl aminopeptidase IV (DAP-IV), sucrase, lactase, and trehalase were studied in 14 different human colorectal cancer cell lines. The effect of sodium butyrate, a known differentiating agent, and cell growth on the activities of these enzymes was also examined. All 14 cell lines exhibited brush border membrane enzyme activities, and in general, the activity of Alkpase, aminopeptidase, and DAP-IV was much higher than the disaccharidases. However, the specific enzyme activities varied among different cell lines. The induction of Alkpase activity by sodium butyrate occurred in most of the 14 cell lines (2- to 123-fold), while induction of the other enzyme activities was observed in several (1.5- to 3.5-fold). In some instances, butyrate caused a decrease in enzyme activity. There was no statistically significant correlation between the induction of Alkpase activity and that of other enzyme activities by sodium butyrate. Levels of aminopeptidase and DAP-IV activity were found to be dependent on cell density and increased 3- to 4-fold by the tenth day in most of the cell lines. Sodium butyrate altered the subcellular distribution pattern of the disaccharidases, causing a significant increase in activity associated with the soluble (cytoplasmic) fraction. Other enzymes such as Alkpase and DAP-IV continued to be predominantly associated with the membrane fraction in butyrate-treated cells. These data suggest that brush border membrane hydrolase activity and the effect of sodium butyrate may provide useful information regarding the differentiation of human colorectal cancer cells.
Cancer Res 1985 Jul
PMID:Effect of growth and sodium butyrate on brush border membrane-associated hydrolases in human colorectal cancer cell lines. 400 36

The expression of small intestinal hydrolases associated with the enterocyte brush border membrane was studied in human colon cancers and foetal colons, by means of monoclonal antibodies against human small intestinal sucrase-isomaltase (SI), maltase-glucoamylase (MGA), lactase (L), aminopeptidase N (APN), and dipeptidylpeptidase IV (DPP-IV). The enzymes were visualized by indirect immunofluorescence on cryostat sections of tumors developed in nude mice with 6 human colon carcinoma cell lines (HT-29, Caco-2, SW-480, HRT-18, HCT-8R, and Co-115), of 27 primary colorectal carcinomas from patients, and of human foetal (16 to 20 weeks of gestation) and normal adult small intestines and colons. All 5 monoclonals bound to the brush border of the adult small intestine, but not to that of the adult colon mucosa. Antibodies against SI, APN and DPP-IV also bound to the brush border of the foetal colons, to apical borders in HT-29 and Caco-2 tumors in nude mice, and to brush border-like structures in 7/27 tumors from patients. No binding was observed for MGA and L in either tumors or foetal colons. Binding of anti-SI antibodies to the brush border of the juxta-tumoral mucosal epithelium was observed in 9/11 samples tested. These data indicate that some colon tumors exhibit a typical pattern of enterocytic differentiation which is of foetal type and which involves at least 3 brush border membrane hydrolases. Monoclonal antibodies to small intestinal hydrolases may, therefore, be important tools for identification and characterization of some differentiated colonic tumors.
Int J Cancer 1984 Nov 15
PMID:Immunohistological evidence, obtained with monoclonal antibodies, of small intestinal brush border hydrolases in human colon cancers and foetal colons. 638 73

Differentiated villus intestinal epithelial cells express globotriaosylceramide, the Shiga-like toxin 1 (SLT-1) receptor, and are sensitive to toxin-mediated cytotoxicity, whereas undifferentiated crypt cells neither express Gb3 nor respond to toxin. To investigate if SLT-1 receptors are maturationally regulated in human intestinal cells, we examined the effect of butyrate, a known transcriptional regulator of differentiation genes in many cell types, using cultured colonic cancer-derived epithelial cell lines. Exposure to butyrate increased villus cell marker enzymes such as alkaline phosphatase, sucrase, and lactase, expression of toxin receptors, and sensitivity to SLT-1 in villus-like CaCo-2A and HT-29 cells. These effects were reversibly inhibited by preincubation of CaCo-2A cells with actinomycin D or cycloheximide. Butyrate-treated CaCo-2A cells unable to bind fluoresceinated SLT-1 B subunit were undifferentiated as assessed by alkaline phosphatase activity. HT-29 cells induced to differentiate by another signal, glucose deprivation, upregulated receptor content and response to toxin. Crypt-like T-84 cells responded to butyrate with a modest increase in alkaline phosphatase and toxin binding, but no induction of sucrase or lactase, and no change in sensitivity to toxin. The results demonstrate that expression of SLT-1 toxin receptors and toxin sensitivity are coregulated with cellular differentiation in cultured intestinal cells.
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PMID:Maturational regulation of globotriaosylceramide, the Shiga-like toxin 1 receptor, in cultured human gut epithelial cells. 765 8

Glutamine supplementation has been advocated for patients requiring parenteral nutritional support. However, the direct effect of glutamine on neoplastic cells is poorly understood. We therefore investigated the effects of glutamine on the proliferation, differentiation, and cell-matrix interactions of two human colon carcinoma cell lines (Caco-2 and SW620) adapted to glutamine-free media. Doubling times were calculated by logarithmic transformation of serial cell counts. Alkaline phosphatase, cathepsin C (dipeptidyl peptidase), lactase, and isomaltase expression (markers of differentiation) were assayed by digestion of synthetic substrates. Adhesion to matrix proteins was assessed by colorimetric quantitation of toluidine blue staining of adherent cells. Surface expression of Caco-2 receptors for matrix proteins (integrins) was studied by biotinylation and immunoprecipitation with specific antibodies. Glutamine (1-10 mM) dose-dependently stimulated Caco-2 proliferation on all matrices studied with maximal effect at 7 mM. For instance, Caco-2 doubling time on collagen IV decreased by 57 +/- 0.2% (SE) (P < 0.001). Glutamine inhibited the expression of all four digestive enzymes with maximal inhibition ranging from 10 to 40% (P < 0.05 for all). Adhesion to matrix proteins was markedly diminished (51 +/- 1%, P < 0.01) by glutamine (5 mM) treatment, correlating with decreased alpha 2 and beta 1 integrin subunit surface expression. Glutamine had similar effects on SW620 cells, stimulating proliferation, inhibiting digestive enzyme expression, and diminishing both adhesion and integrin surface expression. Glutamine supplementation modulates the phenotype of at least two human colon carcinoma cell lines, increasing proliferation, decreasing differentiation, and decreasing adhesion to matrix proteins in association with decreased integrin expression. Although the mechanisms of these effects await elucidation, such characteristics would appear to predict more aggressive tumor behavior and raise the possibility that nutritional supplementation with glutamine may be deleterious in patients with cancer.
Cancer Res 1994 Nov 15
PMID:Glutamine modulates phenotype and stimulates proliferation in human colon cancer cell lines. 795 30

Human colon adenocarcinoma cells, treated with deoxycholate for 24 h prior to exposure to 1 mM butyrate, exhibited dose-dependent increases in the activities of three markers of colonic differentiation (alkaline phosphatase, lactase and CEA). Treatment with deoxycholate alone, for 24 h or longer, did not increase the secretion of CEA or the activities of either of the brush border-associated enzyme activities. Increases in differentiation markers were found to be bile acid-specific. Pretreatment with either dehydrocholic acid or cholic acid, even at cytotoxic concentrations, led to no significant butyrate-induced increases in brush-border associated hydrolase activities. The addition of a bacterial superoxide dismutase decreased the short-term cytotoxicity of deoxycholate and increased the maturation-potentiating effects of the bile acid in HCT-116 DO cells. The results of these studies demonstrate that bile acids, which are commonly thought to have tumor promoting activities in vivo, may also have physiological effects which serve to limit carcinogenic processes in the human colon by potentiating tumor cell differentiation.
Cancer Lett 1993 May 14
PMID:Potentiation of butyrate-induced differentiation in human colon tumor cells by deoxycholate. 851 44

Differentiation of human colonic cancer cells at confluency has been correlated to their increased resistance to chemotherapeutic agents. The aim of this study was to determine whether blocking Caco-2 cell differentiation could sensitize the cells to 5-fluorouracil (5-FU) treatment. We show that in cells at confluency, geraniol (400 microM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase). The antiproliferative effect of geraniol (400 microM) together with 5-FU (5 microM) was twice that of 5-FU alone. The cytotoxicity induced by 5-FU was enhanced in the presence of geraniol, as shown by a 50% increase of lactate dehydrogenase release in the culture medium. These effects are related to enhanced intracellular accumulation of 5-FU in the presence of geraniol as shown by a 2-fold increase in intracellular 5-[6-(3)H]FU (1.5 microCi/ml). It is concluded that geraniol sensitizes colonic cancer cells to 5-FU treatment, by increasing the cytotoxicity of the drug, and that this results from the facilitated transport of 5-FU and the blockade of the morphological and functional differentiation of the cancer cells.
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PMID:Geraniol, a component of plant essential oils, sensitizes human colonic cancer cells to 5-Fluorouracil treatment. 1196 Oct 66

Probiotics have been defined by The Food Agricultural Organization/World Health Organization (FAO/WHO) as "live microorganisms which when administered in adequate amounts confer a health benefit to the host." They have been used for centuries in the form of dairy-based fermented products, but the potential use of probiotics as a form of medical nutrition therapy has not received formal recognition. A detailed literature review (from 1950 through February 2004) of English-language articles was undertaken to find articles showing a relationship between probiotic use and medical conditions. Medical conditions that have been reportedly treated or have the potential to be treated with probiotics include diarrhea, gastroenteritis, irritable bowel syndrome, and inflammatory bowel disease (Crohn's disease and ulcerative colitis), cancer, depressed immune function, inadequate lactase digestion, infant allergies, failure-to-thrive, hyperlipidemia, hepatic diseases, Helicobacter pylori infections, genitourinary tract infections, and others. The use of probiotics should be further investigated for possible benefits and side-effects in patients affected by these medical conditions.
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PMID:Probiotics and medical nutrition therapy. 1548 39

Ovarian carcinoma is the fourth most common cause of cancer death in women. The cause and pathogenesis of this disease has remained obscure. Galactose, the hydrolyzing product of the milk sugar lactose, has been hypothesized to be toxic to ovarian epithelial cells and consumption of dairy products and lactase persistence has been suggested to be a risk factor for ovarian carcinoma. In adults, downregulation of lactase depends on a variant C/T-13910 at the 5' end of the lactase gene. To explore whether lactase persistence is related to the risk of ovarian carcinoma we determined the C/T-13910 genotype in a cohort of 782 women with ovarian carcinoma. The C/T-13910 genotype was defined by solid phase minisequencing from 327 Finnish, 303 Polish, 152 Swedish patients and 938 Finnish, 296 Polish and 97 Swedish healthy individuals served as controls. Lactase persistence did not associate significantly with increased risk for ovarian carcinoma in the Finnish (odds ratio [OR]=0.77, 95% confidence interval [CI]=0.57-1.05, p=0.097), in the Polish (OR=0.95, 95% CI=0.68-1.33, p=0.75), or in the Swedish populations (OR=1.63, 95% CI=0.65-4.08, p=0.29). Our results do not support the hypothesis that lactase persistence increases the ovarian carcinoma risk. On the contrary, lactase persistence may decrease the ovarian carcinoma risk at least in the Finnish population.
Int J Cancer 2005 Oct 20
PMID:Lactase persistence and ovarian carcinoma risk in Finland, Poland and Sweden. 1588 May 73

Dairy food consumption has been inconsistently shown to protect against colorectal cancer (CRC) in case-based studies, and no clear benefits against recurrent colonic polyps (CRP) have been reported. Based on population-based studies we have hypothesized that dairy food intake may have anti-CRC effects at both low intake lactase non-persistent (LNP) populations and at high intake lactase persistent (LP) subjects. We separately analyse existing case-based studies and divide origins into high LNP (>or= 80% LNP prevalence), low LNP (prevalence <or= 20%) and mid LNP countries (21-79% prevalence), which coincide with low, high, and mid quantity dairy food intake regions, respectively. Odds ratios and relative risks (RR) of highest versus lowest dairy intake within each group are analyzed together for assessment of protection against CRC and CRP. Eighty studies met stipulated criteria. Thirteen analyzed the effect on recurrent polyps. Forest plots from 2 regions, high LNP (low dairy food intake) RR = 0.84 [95% confidence interval (CI) = 0.73-0.97) and low LNP (high dairy food intake) RR = 0.80 (95% CI = 0.73-0.88) demonstrated significant protection against CRC. In mixed LNP/LP populations (mid dairy food intake) nonsignificant protection was found RR = 0.92 (95% CI = 0.79-1.06). Similar regional analysis for CRP failed to show significant protective effect in any region. This meta-analysis supports that the highest level of dairy food consumption protects subjects in both high and low LNP regions but not in areas with significant mixed LNP/LP populations. In both groups, dairy foods had no effect on polyp formation, suggesting it may only protect against CRC at late stages of promotion. These results raise the possibility that LNP/LP status may be partly responsible for the discrepant results with respect to the relationship between dairy food consumption and CRC.
Nutr Cancer 2006
PMID:The effect of lactose maldigestion on the relationship between dairy food intake and colorectal cancer: a systematic review. 1704 68

Colorectal cancer (CRC) is one of the leading causes of mortality in Western countries. Its putative pathogenesis revolves around genetic and environmental factors, particularly diet. One of the most studied dietary factors, dairy product intake, is still debated as a protective agent. The role of lactose as a candidate prebiotic (stimulating lactic acid bacteria) and its relation to genetic lactase non-persistence (LNP) status has not been evaluated. We undertook a review and analysis of national per capita dairy product consumption, national LNP prevalence, and national CRC mortality rates (CRCM) to determine whether relationships existed among these variables. Data on these three items were obtained from the available literature. A negative binomial regression model was used to compare national LNP status with national CRCM rates for three time periods. Pearson correlation was used to compare national per capita dairy food intake with national CRCM rates for the approximate midpoint time period of reviewed articles. We found that there was a significant positive correlation between per capita dairy food intake and CRCM rates. However, there was also a significant negative correlation between national LNP prevalence and CRCM rates. Population-based studies supported the suggestion that in both homogeneous high and homogeneous low prevalence LNP countries characterized by low and high dairy food intake respectively, dairy food consumption exerted a protective effect against CRC and CRCM rate. Because some population studies contradict the hypotheses that dairy food intake promotes CRC or that LNP status protects against CRC, we hypothesize that dairy food consumption may operate by two distinct mechanisms--one that operates at low doses in LNP subjects and another in high doses in non-LNP subjects.
Nutr Cancer 2006
PMID:Evaluation of relationships among national colorectal cancer mortality rates, genetic lactase non-persistence status, and per capita yearly milk and milk product consumption. 1704 69


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