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)

Experiments are described in which four transplantable rodent tumors (L1210 lymphoid leukemia, P388 lymphocytic leukemia, B16 melanoma, and Walker 256 carcinosarcoma) were used to investigate the antitumor activity of amygdalin MF. Amygdalin MF was given alone and in combination with beta-glucosidase which was administered 1/2 hour prior to amygdalin MF, starting 24 hours after tumor implantation. No antitumor activity was observed in any of the four tumor systems tested with the drug alone or in combined therapy. The combined therapy showed potentiation of toxicity with doses of amygdalin MF greater than or equal to 100 mg/kg.
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PMID:Antitumor activity of amygdalin MF (NSC-15780) as a single agent and with beta-glucosidase (NSC-128056) on a spectrum of transplantable rodent tumors. 120 98

By using p-nitrophenyl-beta-D-glucopyranoside as substrate, beta-glucosidase activity was observed in fetal bovine serum (FBS). This activity could be inhibited by heat inactivation of the serum. Gel chromatography of FBS indicated the presence of beta-glucosidase activity with an apparent molecular mass of 29 kDa. In McCoy's 5A medium supplemented with non-heat inactivated FBS, the diglucoside hypoxoside ([E]-1,5-bis[4'beta-D-glucopyranosyloxy-3'-hydroxyphenyl]pent-4-en - 1-yne) showed cytotoxicity toward B16-F10-BL-6 mouse melanoma cells. In incubations where the media were supplemented with FBS previously heat inactivated at 56 degrees C for 1 h or more, no cytotoxicity was observed in the presence of hypoxoside. The aglucone of hypoxoside, rooperol ([E]-1,5-bis[3',4'-dihydroxyphenyl]pent-4-en-1-yne), showed cytotoxicity regardless of whether the serum was heat inactivated or not. The kinetics of the heat inactivation of the beta-glucosidase activity in FBS coincided with the loss of apparent cytotoxicity of hypoxoside. High performance liquid chromatography analysis showed that rooperol could be generated by incubation of hypoxoside in non-heat inactivated FBS, but that this ability was lost in serum that was heat inactivated for 1 h or longer. Newborn bovine serum did not contain any beta-glucosidase activity whereas it was found in three different commercial sources of FBS. This observation is of practical importance because conventional heat inactivation of FBS at 56 degrees C for 30 min was not sufficient to inactivate the beta-glucosidase activity completely.
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PMID:beta-Glucosidase activity in fetal bovine serum renders the plant glucoside, hypoxoside, cytotoxic toward B16-F10-BL-6 mouse melanoma cells. 801 53

Hypoxoside is the major diglucoside isolated from the corms of the plant family Hypoxidaceae. It contains an unusual E-pent-1-en-4-yne 5-carbon bridging unit with two distal catechol groups to which the glucose moieties are attached. It is non-toxic for BL6 mouse melanoma cells in tissue culture on condition that the fetal calf serum in the medium is heat-inactivated for 1 hour at 56 degrees C in order to destroy endogenous beta-glucosidase activity. The latter catalyses hypoxoside conversion to its cytotoxic aglucone, rooperol, which, when tested as a pure chemical, caused 50% inhibition of BL6 melanoma cell growth at 10 micrograms/ml. Light and electron microscopy revealed that the cytotoxic effect of rooperol manifested as vacuolisation of the cytoplasm and formation of pores in the plasma membrane. Indications of apoptosis were also found. Pharmacokinetic studies on mice dosed intragastrically with hypoxoside showed that it was deconjugated by bacterial beta-glucosidase to form rooperol in the colon. Surprisingly, no hypoxoside or rooperol was detectable in the serum. Only phase II biotransformation products (sulphates and glucuronides) were present in the portal blood and bile. In contrast, however, in human serum after oral ingestion of hypoxoside, the metabolites can reach relatively high concentrations. Rooperol metabolites isolated from human urine were non-toxic for BL6 melanoma cells in culture up to a concentration of 200 micrograms/ml. In the presence of beta-glucuronidase, which released rooperol from the metabolites, 50% growth inhibition was achieved at a 75 micrograms/ml metabolite concentration. The supernatant of a human melanoma homogenate could also cause deconjugation of the metabolites to form rooperol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Morphological characterisation of the cell-growth inhibitory activity of rooperol and pharmacokinetic aspects of hypoxoside as an oral prodrug for cancer therapy. 854 43

The antimetastatic activity of ten compounds structurally related to nojirimycin A was examined using a pulmonary metastatic model of mouse B16 melanoma. Nojirimycin B, deoxynojirimycin, D-gluco-delta-lactam, CP3068 and CP3069 are structural analogues of nojirimycin A, and showed potent or moderate antimetastatic activities. Nojirimycin A, nojirimycin B, deoxynojirimycin and D-gluco-delta-lactam showed potent or moderate inhibitory activities against alpha-glucosidase, beta-glucosidase and beta-mannosidase, but CP3068 and CP3069 in which the structures were related to D-gluco-delta-lactam showed no inhibitory activities. CP3041, CP3042, CP3043, CP3045 and CP3048 are analogues of sodium D-glucaro-delta-lactam (ND2001), a carboxy derivative of nojirimycin A, and showed potent or moderate antimetastatic activities. But no analogue was superior to ND2001 concerning with antimetastatic and anti-beta-glucuronidase activities. CP3041 and CP3042 showed potent and moderate inhibitory activities against beta-glucuronidase, respectively, but CP3043, CP3045 and CP3048 showed little or no activities.
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PMID:Inhibition of mouse tumor metastasis with nojirimycin-related compounds. 862 56

The dichotomy of cellular transformation versus differentiation does not preclude the hypothesis of a unified underlying mechanism that can switch either way as a result of growth factors, cell-membrane receptors, secondary messengers, integrating switch kinases and/or nuclear receptors. Its study for biopharmaceutical and biotechnological applications requires a methodology capable of dealing with such pleiotropy. In the multiprobe-multiparameter approach, one must remain wary of cumulative toxic effects and misinterpretations. 'Smart' instrumentation does not mean 'smart' probes. It turns out that the cell's own endogenous probes, the fluorescent coenzymes, may be akin to 'smart' probes, open to study in situ of many-fold interrelated pathways in cell energetics and dynamics. Resolution at the micro- and even nano-compartment levels is not altogether impossible. Thus an innovative search in terms of what may be called 'intracellular reconnaissance with fluorescent probes and biopharmaceuticals' necessitates recourse to multiple tentative probings along the pleiotropic mechanisms as far in resolution as one can go. Among the characteristic findings using this approach are: (i) morphometric alterations in the mitochondria and melanosomes of melanoma cells treated with azelaic acid; (ii) deregulation of mitochondrial control and extramitochondrial metabolism in similarly treated cells; (iii) considerable acceleration of NAD(P) transient kinetics in atractylate-treated L sarcoma cells; (iv) alterations of mitochondria and Golgi in fusion-deficient myoblasts; (v) tentative recognition of beta-glucosidase deficiency in Gaucher disease cells by the use of fluorescent and fluorogenic lysosomal probes; and (vi) UVA-induced accumulation of Schiff bases (a kind of accelerated photo-aging) in yeast and kidney epithelial cells. Because these studies utilize probing at whatever points along the concerned pathways become accessible, at first glance they may look disconnected. What and where is the connecting thread, for instance, between studying melanoma metabolism, melanosome morphometry, hepatocyte organelle morphogenesis and transformation, myotube organelle morphogenesis and fusion-non-fusion, and lysosomal activity in gene-deficient cells? In the mapping of the regulatory and deregulatory mechanisms involved in the switching of differentiation or transformation, each of the above topics carries an information content towards resolution of the pleiotropic puzzle. The integration of such information with increasing resolution and access to intracellular microdomains may ultimately allow focus on the precise target, the switch from differentiation to transformation or vice versa.
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PMID:Multiprobe fluorescence imaging and microspectrofluorimetry of cell transformation and differentiation: implications in terms of applied biochemistry and biotechnology. 1033 48

To develop a new skin whitening agent, arbutin-beta-glycosides were synthesized and evaluated for their melanogenesis inhibitory activities. Three active compounds were synthesized via the transglycosylation reaction of Thermotoga neapolitana beta-glucosidase and purified by recycling preparative HPLC. As compared with arbutin (IC(50 )= 6 mM), the IC(50 )values of these compounds were 8, 10, and 5 mM for beta-D -glucopyranosyl-(1-->6)-arbutin, beta-D: -glucopyranosyl-(1-->4)-arbutin, and beta-D -glucopyranosyl-(1-->3)-arbutin, respectively. beta-D: -Glucosyl-(1-->3)-arbutin also exerted the most profound inhibitory effects on melanin synthesis in B16F10 melanoma cells. Melanin synthesis was inhibited to a significant degree at 5 mM, at which concentration the melanin content was reduced to below 70% of that observed in the untreated cells. Consequently, beta-D: -glucopyranosyl-(1-->3)-arbutin is a more effective depigmentation agent and is also less cytotoxic than the known melanogenesis inhibitor, arbutin.
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PMID:Inhibitory effects of arbutin-beta-glycosides synthesized from enzymatic transglycosylation for melanogenesis. 1804 Jun 3