Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.21 (beta-glucosidase)
 3,280 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A search for an abundant and economical source of isoflavones, particularly genistein, led to the discovery that the erythromycin-producing organism Saccharopolyspora erythraea also produces this promising new cancer-prevention agent. Erythromycin fermentation is a large-scale, soybean-based process used world-wide for the commercial production of this medically important antibiotic. Results from this study indicate that genistin (the glucoside form of genistein), which is added to the fermentation in the soybean media, was converted to genistein through the action of a beta-glucosidase produced by the organism. Genistein was co-extracted with erythromycin from the fermentation broth, then separated from erythromycin during the second step of the purification process for the production of erythromycin.
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PMID:Isolation of isoflavones from soy-based fermentations of the erythromycin-producing bacterium Saccharopolyspora erythraea. 916 54

This investigation studied the effects of a shift from a well-balanced mixed diet to a lacto-vegetarian diet on the mutagenic activity in urine and feces and on some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta-glucosidase, and sulphatase). Three months after the shift to the lacto-vegetarian diet, there was a significant decrease in mutagenic activity in urine and feces, beta-glucuronidase, beta-glucosidase, and sulphatase per gram feces wet weight. In contrast, the fecal mutagenic activity and the enzyme activities remained unchanged if expressed per daily output. However, the urinary mutagenic activity expressed as total daily output decreased. Part of the explanation for the decreased fecal mutagenic activity and the decreased enzyme activities is obviously a dilution effect, because much of the increased fecal weight after the shift in diet was associated with a higher water content.
Cancer Detect Prev 1997
PMID:Dietary influence on some proposed risk factors for colon cancer: fecal and urinary mutagenic activity and the activity of some intestinal bacterial enzymes. 916 43

Recent evidence suggests that resistant starch (RS) is the single most important substrate for bacterial carbohydrate fermentation in the human colon. During two 4-wk periods. 12 healthy volunteers consumed a controlled basal diet enriched with either amylomaize starch (55.2 +/- 3.5 g RS/d; high-RS diet) or available cornstarch (7.7 +/- 0.3 g RS/d; low-RS diet). Approximately 90% of the RS consumed disappeared during intestinal passage; increased fermentation was verified by elevated breath-hydrogen excretion. During the high-RS diet, fecal wet and dry weight increased 49% and 56%, respectively (P < or = 0.005), whereas stool water content did not change significantly. Fecal concentrations and daily excretion of short-chain fatty acids were not different in the two study periods. During the high-RS diet, bacterial beta-glucosidase activity decreased by 26% (P < or = 0.05). Fecal concentrations of total and secondary bile acids were significantly lower during the high-RS than during the low-RS period [a decrease of 30% (P < or = 0.05) and 32% (P < or = 0.01), respectively, in total and secondary bile acids] whereas concentrations of primary bile acids were unaffected by RS consumption. During the high-RS diet, fecal concentrations of total neutral sterols decreased by 30% (P < or = 0.005) and fecal concentrations of 4-cholesten-3-one decreased by 36% (P < or = 0.05). These data suggest that RS has potentially important effects on bacterial metabolism in the human colon that may be relevant for cancer prevention.
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PMID:Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention. 944 Mar 88

We describe a novel version of antibody-directed enzyme prodrug therapy (ADEPT), with the use of amygdalin as prodrug. Amygdalin is a naturally occurring cyanogenic glycoside, which can be cleaved by sweet almond beta-glucosidase to yield free cyanide. If amygdalin could be activated specifically at the tumour site, then malignant cells would be killed without the systemic toxicity usually associated with chemotherapy. To this end, we have conjugated beta-glucosidase to a tumour-associated monoclonal antibody (MAb) (HMFG1) and the conjugate has been tested in vitro for specificity and cytotoxicity subsequent to activation of amygdalin. Amygdalin was cytotoxic to HT1376 bladder cancer cells only at high concentrations, whereas the combination of amygdalin with HMFG1-beta-glucosidase enhanced the cytotoxic effect of amygdalin by 36-fold. When 2 concentrations of HMFG1-beta-glucosidase were compared, the toxic effect was dose dependent. The cytotoxicity of amygdalin was also enhanced by the MAb-enzyme conjugate even when the unbound conjugate was removed from the medium prior to exposure to amygdalin and the cells were washed. In addition to the cytotoxic effect, we also demonstrated specificity, using a MAb-enzyme conjugate that does not recognise the HT1376 bladder cancer cells. Finally, we studied the cytotoxic effect of the conjugate in co-culture of HMFG1-positive and-negative cell lines (HT 1376 and U87MG cells). We demonstrated that the rate of surviving cells corresponds well to the percentage of U87MG (HMFG1-negative) cells in the flask. Our findings indicate that ADEPT is more effective than non-directed enzyme activation of a prodrug and can result in a non-toxic cancer therapy.
Int J Cancer 1998 Dec 09
PMID:In vitro cytotoxicity following specific activation of amygdalin by beta-glucosidase conjugated to a bladder cancer-associated monoclonal antibody. 983 64

Diagnostic difficulties of Gaucher disease, a disorder resulted from a deficient activity of glucocerebrosidase is reported. Gaucher disease was described in the 16 year old male, 5 years after manifestation of the very first symptoms (fracture and osteomyelitis). At the age of 14, the cirrhosis due to viral hepatitis accompanied with splenomegaly was diagnosed. This findings was not associated with the earlier osseous disorders. Histopathologic examination of the removed spleen facilitate the diagnosis. The second case refers to 20 year old female. Clinical symptoms and additional test pointed to malignant neoplasm of thyroid, the reproductive organs or cancer of indistinguishable primary focus with metastases in the liver. Trepanobiopsy of bone marrow had made an accurate diagnosis possible, while determination of beta-glucosidase activity in peripheral white blood cells, chitotriosidase activity, and molecular investigations of gene specific to beta-glucocerebrosidase proved it.
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PMID:[Diagnostic difficulties in Gaucher disease: report of two cases]. 1033 43

Prebiotics, in particular the chicory derived beta(2-1) fructans, have been shown to exert cancer protective effects in animal models. The present study was carried out to determine the effects of two chicory fructans--oligofructose (RaftiloseP95; average degree of polymerization DP = 4) and long chain inulin (RaftilineHP; average DP = 25), on apoptosis and bacterial metabolism associated with carcinogenesis. Eighteen rats were fed a stock diet for one week. Three groups of six animals were then fed one of three diets: basal, basal with oligofructose (5%w/w) or basal with long chain inulin (5%w/w), for a three week period. All animals were then dosed with 1,2-dimethylhydrazine and killed 24 h later. The mean number of apoptotic cells per crypt was significantly higher in the colon of rats fed oligofructose (P = 0.049) and long chain inulin (P = 0.017) as compared to those fed the basal diet alone. This suggests that oligofructose as well as the long chain inulin exert protective effects at an early stage in the onset of cancer, as the supplements were effective soon after the carcinogen insult. Comparison of the apoptotic indices between the two oligosaccharide diets showed no significant difference even though the mean apoptotic index was higher in animals fed long chain inulin. For all animals, apoptosis was significantly higher in the distal colon as compared to the proximal colon (P = 0.0002) however no significant site specific effect of diet occurred. There were no significant dietary effects on bacterial enzyme activities or ammonia concentration despite a trend towards increased colonic beta-glucosidase and reduced ammonia concentration during the oligosaccharide diets. This is the first time that a significant effect of chicory fructans on apoptosis has been shown and the results contribute to the growing evidence that chicory fructans may have cancer preventing properties.
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PMID:Stimulation of apoptosis by two prebiotic chicory fructans in the rat colon. 1115 39

The number of colorectal tumors per mouse induced by 1,2-dimethylhydrazine in transgenic (Tg) mice carrying human c-Ha-ras genes was significantly reduced by ingestion of apple pectin (AP) or a culture condensate of Bifidobacterium longum(MB) compared with a control diet and non-Tg mice. However, there were no differences in the composition of fecal flora, water content, beta-glucuronidase and beta-glucosidase activities, and concentrations of organic acids and putrefactive products in the feces between the AP or MB diet and the control diet, or between the Tg mice and non-Tg mice. The concentration of secondary bile acids in the MB diet group was higher than that in the control group. These results suggested that there was no relationship between prevention of colorectal tumors in Tg mice and the AP or MB diet, or improvement of the intestinal environment due to these functional foods.
J Exp Clin Cancer Res 2001 Mar
PMID:Effect of bacterial metabolism in the intestine on colorectal tumors induced by 1,2-dimethylhydrazine in transgenic mice harboring human prototype c-Ha-ras genes. 1137 Aug 30

Multidrug-resistant (MDR) cancer cells have been shown to have an accumulation of glucosylceramide (GlcCer). In this study, we aim at localizing, at subcellular level, where these lipids accumulate. Neutral lipids and phospholipid containing organelles have been identified using confocal fluorescence microscopy and microspectrofluorometry by monitoring the emission of the fluorescent probe Nile-red. Data from confocal fluorescence microscopy analysis shows accumulation of neutral lipids in cytoplasmic droplets of MDR human carcinoma MCF7R cells. Microspectrofluorometric measurements show an increase of the gold-yellow emission intensity in MCF7R cells, corresponding to neutral lipids. Similar observations were made in human MDR vincristine-HL60 and doxorubicin-KB selected cells. Total cellular glucosylceramide (GlcCer) measurements using [(3)H]-palmitic acid and thin layer chromatography show a significant increase of GlcCer in MCF7R cells. Moreover, MCF7R cells treated with fluorescent GlcCer-bodipy exhibit an accumulation of this lipid in cytoplasmic droplets. Treatment of MCF7R cells with 1-phenyl-2-palmitoylamino-3-morpholino-1-propanolol (PPMP), a potent inhibitor of GlcCer synthase, attenuates the Nile-red fluorescence emission emanating from these structures and reverses MDR. Moreover, Golgi compartments stained with fluorescent PPMP-bodipy, show an increase in the Golgi compartments density. Treatment of MCF7R cells with cyclosporine A (CSA), tamoxifen (TMX) and 3'-azido-3'deoxythymidine (AZT) leads to the same effect observed in the presence of PPMP. Treatment of MCF7 and MCF7R with the beta-glucosidase inhibitor conduritol beta-epoxide (CBE) significantly increases resistance to daunorubicin only in MCF7R cells. These data demonstrate also that: (i) CSA, an inhibitor of MDR, has an additional target in addition to P-glycoprotein; and (ii) TMX (used in breast cancer treatment and prevention) and AZT (used in the treatment of HIV) could have side effects by disturbing lipid metabolism and inhibiting many cellular functions required in normal cells.
Int J Cancer 2001 Oct 15
PMID:Elevation of glucosylceramide in multidrug-resistant cancer cells and accumulation in cytoplasmic droplets. 1166 92

A number of enzyme/prodrug activation approaches for the treatment of cancer have been reported to date with varying success. We describe progress in the development of a system based on a beta-glucosidase enzyme in combination with a naturally occurring "prodrug," the sugar linamarin, which releases the cytotoxin cyanide. A recombinant fusion protein, composed of an scFv (MFE-23) reactive against carcinoembryonic antigen (CEA) and a plant-derived beta-glucosidase (linamarase), was produced and its cytotoxic potential was investigated. The fusion protein was expressed in a supersecretory mutant strain of Saccharomyces cerevisiae and purified by affinity chromatography. Extensive functional in vitro characterisation of the fusion protein showed that it retained antigen binding activity but that its catalytic activity was impaired, a problem not related to its fusion with the scFv. Nevertheless, we demonstrated complete tumour cell killing at doses of prodrug that are completely nontoxic to nontargeted cells. Preliminary in vivo characterisation showed that extensive glycosylation of the fusion protein caused its rapid clearance through the hepatic route. Aggregational properties also led to poor pharmacokinetics. Furthermore, we present some data analysing the mode of cell death resulting from exposure to this system. Enzymic catalysis of the substrate generates cyanide, a metabolic poison that asphyxiates cells and leads them to a necrotic-like cell death. This system has been called antibody-guided enzyme nitrile therapy (AGENT).
Int J Cancer 2002 May 01
PMID:Antibody-guided enzyme therapy of cancer producing cyanide results in necrosis of targeted cells. 1194 5

In epidemiologic studies on human colorectal tumors, results on the relative protective effect of soluble and insoluble fibers are not consistent. We studied in this work the effect in rats of feeding guar gum or guar gum together with cellulose on the incidence of colorectal tumors induced by 1,2-dimethylhydrazine. The results were as follows: (i) The enhancement of tumor formation by feeding solely guar gum (guar gum group) was suppressed completely when two-thirds of the guar gum was replaced with cellulose (cellulose-guar gum group). The odds ratio for tumor formation was 0.075 (95% CI 0.006-0.936, p = 0.044) for guar gum group vs. no fiber control and 0.833 (0.134-5.167, p = 0.83) for cellulose-guar gum group vs. the control. (ii) In both groups, serum cholesterol and triglyceride levels decreased significantly compared to the no fiber control group, and fecal excretion of total bile acids almost doubled. (iii) In guar gum group rats, the deconjugation activity (beta-glucuronidase, beta-glucosidase) was higher than the control or cellulose-guar gum group rats. (iv) The amount of cecal short-chain fatty acids was almost double in guar gum group rats compared to the cellulose-guar gum group or the control rats, and pH of the cecal content of the guar gum group rats had a tendency to be lower. (v) The concentration of fecal secondary bile acids was extremely low in the younger rats of the guar gum group. From these results, it seemed significant to study the cancer preventive effect of the mixed feeding to experimental animals of water-soluble and insoluble fibers instead of the singular feeding.
Int J Cancer 2002 Aug 01
PMID:Increased incidence rate of colorectal tumors due to the intake of a soluble dietary fiber in rat chemical carcinogenesis can be suppressed by substituting partially an insoluble dietary fiber for the soluble one. 1211 18


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