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PubMed1997

Prednicarbate biotransformation in human foreskin keratinocytes and fibroblasts.

PURPOSE: Evaluation of skin layer-specific prednicarbate (PC) biotransformation, possibly explaining the improved benefit/risk ratio of this topical corticosteroid in atopic dermatitis (1,2). METHODS: Metabolism of PC in keratinocyte and fibroblast monolayers derived from human juvenile foreskin was evaluated. Drug concentration was determined by HPLC/UV-absorption. Accompanying cell viability tests (MTT-tests) were performed to exclude toxic drug effects. RESULTS: Keratinocytes hydrolyzed the double ester PC (2.5 x 10(-5) M) at position 21 to the monoester prednisolone 17-ethylcarbonate (P17EC) which nonenzymatically transformed to prednisolone 21-ethylcarbonate (P21EC). This metabolite was enzymatically cleaved to prednisolone (PD), the main biotransformation product at 24 hours. Fibroblasts, however, showed a distinctively lower enzyme activity. Both, PC and P17EC (or rather P21EC) were hydrolyzed to a minor extent only. The biotransformation pathway, however, was the same. When P17EC was added separately, it transformed to P21EC and again was cleaved by keratinocytes to a much higher extent. Despite of the rather high glucocorticoid concentration MTT-tests proved a non-disturbed cell viability and proliferation rate. CONCLUSIONS: Extrapolating our results to the in-vivo situation, topically applied PC may be metabolized by epidermal cells during skin penetration. A complex mixture of compounds reaches the dermis, whose fibroblasts are barely able to metabolize the steroids. Since skin atrophy is less pronounced with PC as compared to conventional halogenated glucocorticoids, less potent PC metabolites appear to be the dominant species in the dermis.

Administration, Topical↗

PubMed1999

High throughput ribonuclease protection assay for the determination of CYP3A mRNA induction in cultured rat hepatocytes.

1. A rapid 96-well plate based method for the determination of CYP3A mRNA induction in primary rat hepatocytes has been developed which has substantial advantages over current technologies including the ability to test the effect of relatively large numbers of new chemical entities on the expression of CYP3A mRNA in hepatocytes. 2. The ribonuclease protection assay detects changes in mRNA levels in small numbers of hepatocytes by the utilization of a radiolabelled antisense riboprobe that will hybridize CYP3A1 and CYP3A23. Using in situ hybridization techniques in conjunction with Amersham 96-well Cytostar-T scintillating microplates, there is no need for isolation of mRNA. A simple ribonuclease digestion step allows quantitative data to be generated easily within 1 week of hepatocyte isolation. 3. Rat hepatocytes were cultured for 48 h post-isolation on the Cytostar plates coated with a basal matrix of Matrigel. Prototypical CYP3A inducers (dexamethasone and pregnenolone 16alpha-carbonitrile) have been studied using various treatment periods from 0.5 to 24 h. Methylclofenapate and beta-naphthoflavone, prototypical inducers of CYP4A and CYP1A respectively, have been used as controls to show specificity of the [33P]-labelled riboprobe for the CYP3A family. 4. Time-dependent increases in CYP3A mRNA were demonstrated following exposure of hepatocytes to prototypical CYP3A inducers, but not for methylclofenapate or beta-naphthoflavone, so demonstrating specificity for CYP3A mRNA over CYP1A and CYP4A. Analysis of the 24-h induction data demonstrates that significant differences from controls can be determined and that induction potential can be assessed. The system has the potential to screen for overall CYP3A mRNA induction in response to compounds at an early stage in drug research.

Animals↗

PubMed2001

Cytotoxicity effects of di- and tri-hydroxybenzaldehydes as a chemopreventive potential agent on tumor cells.

As part of our earlier search for new compounds with improved biological activities including antioxidant, anti-inflammatory, and tumor growth inhibition activities, we synthesized 2,4,5-trihydroxybenzaldehyde (2,4,5-THBA) from commercially available Sesamol. First we examined the free radical-quenching capacity of 2,4,5-THBA, 3,4-dihydroxybenzaldehyde (3,4-DHBA), and 2,5-dihydroxybenzaldehyde (2,5-DHBA) in vitro by 1,1-diphenyl-1,2-picryhydrazylradical (DPPH) test. The antioxidant bioactivity was also evaluated using the model of t-butyl hydroperoxide (t-BHP)-induced cytotoxicity in rat primary hepatocytes. Finally, three chemicals were tested by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay on human nasopharynx carcinoma cells (KB cells), human hepatoblastoma (HepG2), and human leukemia HL-60 cells. The 2,4,5-THBA shows significant cytotoxicity on HL-60 cells. The results suggest that 2,4,5-THBA may be a potential chemopreventor or chemotherapy agent against HL-60 cells.

Animals↗

PubMed2000

Cysteine chloromethyl and diazomethyl ketone derivatives with potent anti-leukemic activity.

A series of cysteine diazomethyl- and chloromethyl ketone derivatives has been synthesized and evaluated against human B-lineage (Nalm-6) and T-lineage (Molt-3) acute lymphoblastic leukemia cell lines. The chloromethyl ketone compounds showed potent cytotoxicity against these cell lines, with IC50 values in the low micromolar range. The best compounds were N-acetyl-S-dodecyl-Cys chloromethyl ketone (IC50 = 2.0 microM against Nalm-6, 2.3 microM against Molt-3) and N-acetyl-S-trans,trans-farnesyl-Cys chloromethyl ketone (IC50 = 3.0 microM against Nalm-6 and 1.4 microM against Molt-3).

Amino Acid Chloromethyl Ketones↗

PubMed2006

Survival strategy of Erwinia amylovora against copper: induction of the viable-but-nonculturable state.

Copper compounds, widely used to control plant-pathogenic bacteria, have traditionally been employed against fire blight, caused by Erwinia amylovora. However, recent studies have shown that some phytopathogenic bacteria enter into the viable-but-nonculturable (VBNC) state in the presence of copper. To determine whether copper kills E. amylovora or induces the VBNC state, a mineral medium without copper or supplemented with 0.005, 0.01, or 0.05 mM Cu(2+) was inoculated with 10(7) CFU/ml of this bacterium and monitored over 9 months. Total and viable cell counts were determined by epifluorescence microscopy using the LIVE/DEAD kit and by flow cytometry with 5-cyano-2,3-ditolyl tetrazolium chloride and SYTO 13. Culturable cells were counted on King's B nonselective solid medium. Changes in the bacterial morphology in the presence of copper were observed by scanning electron microscopy. E. amylovora entered into the VBNC state at all three copper concentrations assayed, much faster when the copper concentration increased. The addition of different agents which complex copper allowed the resuscitation (restoration of culturability) of copper-induced VBNC cells. Finally, copper-induced VBNC cells were virulent only for the first 5 days, while resuscitated cells always regained their pathogenicity on immature fruits over 9 months. These results have shown, for the first time, the induction of the VBNC state in E. amylovora as a survival strategy against copper.

Colony Count, Microbial↗

PubMed2002

New propargyl thioquinolines--synthesis, antiproliferative activity in vitro and structure-activity relationships.

The series of the propargyl thioquinolines has been prepared on the basis of the reaction of thioquinanthrene (1) (1,4-dithiino[2,3-c:5,6-c']-diquinoline) with sodium alkoxides. Some of these compounds have revealed good antiproliferative activity in vitro against the cells of human and murine cancer lines. 13C NMR spectra were measured for the studied compounds to examine the electronic properties-activity relationships. A regression study on 10 compounds showed a linear correlation of antiproliferative activity with electronic properties, expressed as the 13C NMR chemical shift for C-4 carbon atom (R2 = 0.97). It was found that compounds with chemical shift for C-4 value falling in the range of 135-140 ppm exhibited significant antiproliferative activity, while compounds which possess moderate or low activity are located in the range 140-165 ppm. This finding leads to the expectation that the antiproliferative activity of propargyl thioquinolines can be predicted using the 13C NMR chemical shift value of their C-4 carbon atom.

Animals↗

PubMedDate not supplied

[Superoxide dismutase activity of human plasma; the effect of Cu2+-complex compounds].

The superoxide-dismutase (EC 1.15.1.1) activity was revealed in blood plasma after its successive treatment with alcohol, chloroform and one- or two-substituted phosphate. Its value is the highest when treating plasma with KH2PO4. The boiling of the supernatant liquid obtained after addition of K2HPO4 leads to a complete loss of the activity. The treatment of plasma with KH2PO4 provides higher stability of the enzyme to thermal actions. The analysis of EPR-spectra has shown the presence of different complex compounds of copper ions in the supernatant liquid. Certain experiments with the use of aqueous solutions of CuCl2 and histidine have shown that Cu2+ inhibits the superoxide-dismutase activity in samples treated with KH2PO4 and increases it in samples treated with K2HPO4.

Copper↗

PubMed1992

Assessment of cytotoxicity assays as predictors of ocular irritation of pharmaceuticals.

We have evaluated the use of cytotoxicity assays in vitro as an alternative to predicting ocular irritation potential in animals. Three different measures of cytotoxicity--leucine incorporation into protein, MTT dye reduction, and neutral red uptake--were measured in a presumed target cell, corneal epithelial cells from rabbit, as well as in a nontarget cell, V79 (Chinese hamster lung fibroblasts). An IC50 value was determined for each endpoint in one or both target cells for a series of 27 commercially available compounds and 56 in-house materials from a variety of chemical classes (carbonitriles, imidazoles, substituted benzenes, aromatic acids, peptides, phenols, esters, etc.). Analysis of the data by Spearman rho rank correlation and Pearson's correlation indicated that none of the endpoint-target cell combinations used here accurately predicts in vivo irritation potential for this group of compounds. The MTT dye reduction endpoint gave the best overall correlation, regardless of target cell, but still had a correlation coefficient below -0.5. We conclude that the measurement of cytotoxicity is of limited value as an alternative assay for the classes of materials studied here.

Animals↗

PubMed2006

Linker-modified triamine-linked acridine dimers: synthesis and cytotoxicity properties in vitro and in vivo.

The preparation and cytotoxicity properties of a series of N(epsilon)-substituted triamine-linked acridine dimers are described. Most acridine dimer derivatives reveal highly potent in vitro cytotoxicity properties and DNA binding activity. Several acridine dimers were selected to study their action in vivo. These acridine dimers have demonstrated a narrow safe margin, as has adriamycin, but higher maximum tolerate dose (MTD) in comparison with that of adriamycin in ICR mice. The acridine dimers also demonstrated various anit-COLO 205 solid tumor activities in vivo. Compound 1 has shown the most potent solid tumor inhibition.

Acridines↗

PubMed1999

Use of calcium peroxide to provide oxygen for contaminant biodegradation in a saturated soil.

Laboratory studies were conducted in solid-phase reactors on a silty loam contaminated with bis-(2-ethylhexyl) phthalate (BEHP) to determine the conditions under which calcium peroxide (CaO(2)) would promote the aerobic bioremediation of water-saturated soil. Closed 500 ml solid-phase reactors were operated to determine whether CaO(2) stimulated the biodegradation of BEHP in saturated soil. Ex situ bioremediation conditions were then simulated by mixing water-saturated soil for 6 h before placing the soil in three vented, 2 l solid-phase reactors for 50 days. Biodegradation of BEHP was quantified using four different measurements of microbial activity: (1) oxygen concentrations in the reactor gas; (2) bacterial colony-forming units (CFU); (3) fungal CFU; and (4) 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyl tetrazolium chloride dehydrogenase activity (INT-DHA). CaO(2) released molecular O(2), which retarded dewatering but substantially enhanced BEHP biodegradation. After 20 days, BEHP in the amended reactor was reduced from 20.3 to roughly 5 g kg(-1) vs. 15 g kg(-1) in the reactor without CaO(2). Bacterial growth was favored over fungal growth at elevated moisture and BEHP levels.

Bacteria↗

PubMed1997

Histopathological changes induced by zinc hydroxide in rat lungs.

Rat lungs were histologically examined at 1, 7, 14 and 28 days following a single intratracheal instillation of zinc hydroxide (1 mM). After one day of treatment, no confirmatory findings were noted. The zinc hydroxide injections were followed by an increase in proliferating cell nuclear antigen labeling indices in both alveolar macrophages and terminal bronchioles. After 7 days, the zinc hydroxide-treated lungs showed thickening of the interstitium with infiltration by alveolar macrophages, and an increase in the grade of Masson's trichrome staining (collagen fiber) in the alveolar interstitium. Thereafter, these morphological changes disappeared. The vehicle- and zinc sulfate (1 mM)-exposed lungs had no abnormalities at any time point. Formazan deposits in alveolar macrophages, formed as a result of nitro blue tetrazolium reduction, were increased in zinc hydroxide-treated lung slices, suggesting that zinc hydroxide stimulated super oxide anion generation from alveolar macrophages. These results show that zinc hydroxide can induce morphological alterations of rat lungs.

Animals↗

PubMed1998

Alzheimer's amyloid precursor protein alpha-secretase is inhibited by hydroxamic acid-based zinc metalloprotease inhibitors: similarities to the angiotensin converting enzyme secretase.

The 4 kDa beta-amyloid peptide that forms the amyloid fibrils in the brain parenchyma of Alzheimer's disease patients is derived from the larger integral membrane protein, the amyloid precursor protein. In the nonamyloidogenic pathway, alpha-secretase cleaves the amyloid precursor protein within the beta-amyloid domain, releasing an extracellular portion and thereby preventing deposition of the intact amyloidogenic peptide. The release of the amyloid precursor protein from both SH-SY5Y and IMR-32 neuronal cells by alpha-secretase was blocked by batimastat and other related synthetic hydroxamic acid-based zinc metalloprotease inhibitors, but not by the structurally unrelated zinc metalloprotease inhibitors enalaprilat and phosphoramidon. Batimastat inhibited the release of the amyloid precursor protein from both cell lines with an I50 value of 3 microM. Removal of the thienothiomethyl substituent adjacent to the hydroxamic acid moiety or the substitution of the P2' substituent decreased the inhibitory potency of batimastat toward alpha-secretase. In the SH-SY5Y cells, both the basal and the carbachol-stimulated release of the amyloid precursor protein were blocked by batimastat. In contrast, neither the level of full-length amyloid precursor protein nor its cleavage by beta-secretase were inhibited by any of the zinc metalloprotease inhibitors examined. In transfected IMR-32 cells, the release of both the amyloid precursor protein and angiotensin converting enzyme was inhibited by batimastat, marimastat, and BB2116 with I50 values in the low micromolar range, while batimastat and BB2116 inhibited the release of both proteins from HUVECs. The profile of inhibition of alpha-secretase by batimastat and structurally related compounds is identical with that observed with the angiotensin converting enzyme secretase suggesting that the two are closely related zinc metalloproteases.

Alzheimer Disease↗

PubMed2006

New stilbenoids from Pholidota yunnanensis and their inhibitory effects on nitric oxide production.

Six new stilbenoids, a (bibenzyldihydrophenanthrene) ether designated phoyunnanin D (1), a bis(dihydrophenanthrene) ether designated phoyunnanin E (2), and four stilbenes designated phoyunbene A-D (3-6), were isolated from the air-dried whole plant of Pholidota yunnanensis ROLFE. The new compounds were identified as 7-[2-(3-hydroxyphenethyl)-4-hydroxy-6-methoxyphenoxy]-4-hydroxy-2-methoxy-9,10-dihydrophenanthrene (1), 1-[(9,10-dihydro-4-hydroxy-2-methoxy-7-phenanthrenyl)oxy]-4,7-dihydroxy-2-methoxy-9,10-dihydrophenanthrene (2), trans-3,3'-dihydroxy-2',4',5-trimethoxystilbene (3), trans-3,4'-dihydroxy-2',3',5-trimethoxystilbene (4), trans-3,3'-dihydroxy-2',5-dimethoxystilbene (5), and trans-3-hydroxy-2',3',5-trimethoxystilbene (6) based on spectroscopic evidence. Furthermore, the inhibitory effects of compounds 1-6 on nitric oxide production in a murine macrophage-like cell line (RAW 264.7) activated by lipopolysaccharide and interferon-gamma were examined.

Animals↗

PubMed2005

Differential effects of diallyl disulfide on neuronal cells depend on its concentration.

Diallyl disulfide (DADS) is one of the organosulfur compounds of garlic. The effects of DADS on neuronal cells have not clearly been established. We investigated its effects on the viability of neuronal cells (N18D3 cells), the levels of free radical and membrane lipid peroxidation, and the cell signals, such as phosphatidylinositol 3-kinase (PI3K)/Akt and glycogen synthase kinase-3 (GSK-3). When N18D3 cells were treated with several concentrations of DADS, the viability was not affected up to 25 microM, however, decreased at higher than 25 microM. The levels of free radicals and membrane lipid peroxidation were increased in a dose-dependent manner, especially at higher than 25 microM. The treatment of N18D3 cells with 25 microM DADS slightly increased the expressions of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3, but the treatment with 100 microM significantly reduced them. To evaluate whether low concentration of DADS, up to 25 microM, had protective effect on oxidative stress-injured N18D3 cells, the viability of N18D3 cells (pretreated with DADS for 2h versus not pretreated) was evaluated 24h after their exposure to 100 microM H(2)O(2) for 30 min. Compared to the cells treated with only 100 microM H(2)O(2), the pretreatment with 25 microM DADS increased the viability, and the expressions of p85a PI3K, phosphorylated Akt and phosphorylated GSK-3. These results indicate that low concentration of DADS has protective effects on N18D3 cells, whereas high concentration is rather cytotoxic. Therefore, some specific optimum concentration of DADS may be a new potential therapeutic strategy for oxidative stress-injury in vitro model of neurodegenerative diseases.

Allyl Compounds↗

PubMed2001

The selenoorganic compound ebselen suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats.

Ebselen (2-phenyl-1,2-benzoisoselenazol-3[2H]-one) is a selenoorganic compound containing selenium that has various pharmacological effects, including anti-inflammatory and antioxidant activity. Kupffer cells, residual hepatic macrophages, play an important role in the development of liver injury by producing free radicals and cytokines. The aim of this study is to evaluate whether ebselen suppresses macrophage-associated liver injury in rats. In vivo, we examined the effects of ebselen on liver injury, induced by Propionibacterium acnes and lipopolysaccharide (P. acnes-LPS), in rats where hepatic macrophages are considered to be primarily involved in injury development. Ebselen administration reduced the incidence of death following hepatic failure by P. acnes-LPS (82% vs. 20%, p<0.05). Serum levels of alanine aminotransferase, at 5 h after LPS administration, were significantly lower in the ebselen-treated group than in the control group (202.4+/-100.3 IU/l vs. 558.4+/-146.4 IU/l, p<0.05). Histological evidence of injury, such as necrosis, hemorrhage, and degeneration, was also suppressed by ebselen. Further, to assess the mechanisms involved, we investigated the production of cytokines and superoxide anions produced by activated hepatic macrophages in vivo. Serum levels of TNF alpha, interleukin-18 (IL-18)/IFN gamma-inducing factor (IGIF), and interferon gamma (IFN gamma) at 1 h after LPS administration were significantly lower in the ebselen-treated group. Formazan depositions, which were generated by the perfusion of the liver with nitroblue tetrazolium, were also observed less frequently in the ebselen treated group, suggesting a suppression in the release of superoxide anion from activated hepatic macrophages. In addition, we examined the effects of ebselen on cytokine production and mRNA expression, in vitro, using rat primary Kupffer cell culture. Ebselen also inhibited TNF alpha production and mRNA expression in vitro. These data imply that ebselen suppresses liver injury by inhibiting the production and/or release of proinflammatory cytokines and superoxide from activated hepatic macrophages. These data also suggest that ebselen is potent in the prevention of hepatic injury, such as endotoxemia, where hepatic macrophage activation has been implicated.

Alanine Transaminase↗

PubMed1994

In vitro and in vivo cytotoxicity of gossypol against central nervous system tumor cell lines.

Gossypol is a lipid soluble polyphenolic compound isolated from cotton seed oil which has been previously shown to have antiproliferative activity in vitro against a variety of human solid tumor cell lines. It has been extensively tested in clinical trials as a male contraceptive agent and found to be well tolerated. Its mechanism of action is thought to be inhibition of cellular energy metabolism. It inhibits glycolysis through inhibition of LDH isoenzyme type 5, and it inhibits mitochondrial oxidative phosphorylation and electron transport. We tested the in vitro antiproliferative effect of gossypol against four well characterized human glioma cell lines, HS 683, U373, U87 and U138, and one rat glioma cell line, C6, using the colorimetric Microculture Tetrazolium Assay (MTT). Cytotoxicity was found to be concentration and time dependent and increased with incubation times up to 8 days. The relative sensitivity of the glioma cell lines to gossypol at 48 hour incubation correlated with their respective LDH isoenzyme profiles, with the more sensitive cell lines expressing increased cathodal LDH isoenzymes (LDH5). The in vitro cytotoxicity of gossypol to these CNS tumor lines was compared to the other non central nervous system solid tumor cell lines which had been previously reported as being sensitive to gossypol, including SW-13 (adrenal), MCF-7 (breast), T47-D (breast), and HeLa (cervical). Additional lines tested included SK-MEL-3 (melanoma), Colo 201 (colon) and BRW, a line established in our laboratory from a patient with a Primitive Neuroectodermal tumor. C6, HS 683, and BRW had similar IC50s as the sensitive solid tumor cell lines. U373, U87 and U138 had significantly less sensitivity at 48 hours. There was greater cytotoxicity and no significant differences in the IC50s between any of cell lines at 8 day incubations. Additionally, we tested the cytotoxicity of gossypol against BRW in vivo, using the nude mouse xenograft model. Gossypol, given at a dose of 30 mg/kg per day five days a week for four weeks orally via gavage, was found to decrease the mean tumor weight of treated xenografts by more than 50% as compared to untreated xenografts. These findings suggest that gossypol has potential for further study as an agent for the treatment of primary CNS malignancies.

Animals↗

PubMed1978

The role of iron in prostaglandin synthesis: ferrous iron mediated oxidation of arachidonic acid.

Arachidonic acid (AA) is the essential substrate for production of platelet endoperoxides and thromboxanes. Iron or heme is an essential cofactor for the peroxidase, lipoxygenase and cyclo-oxygenase enzymes involved in formation of these products. The present study has examined the direct interactions between iron and arachidonic acid. Iron caused the oxidation of AA into more polar products which could be detected by UV absorbtion at 232 nM or the thiobarbituric acid (TBA) reaction. High pressure liquid chromatography, chem-ionization and electron-impact mass spectrometry and nuclear magnetic resonance spectroscopy suggest that the major product was a hydroperoxide of AA. Ferrous iron (Fe++) and oxygen were absolute requirements. Fe++ was converted to the ferric iron (Fe+++) state during oxidation of AA, but Fe+++ could not substitute for Fe++. No other enzymes, cofactors or ions were involved. Conversion of AA to a hydroperoxide by Fe++ was inhibited by the antioxidant, 2, (3)-Tert-butyl-4-hydroxyanisole, the radical scavenger, nitroblue tetrazolium, and iron chelating agents, including EDTA, imidazole and dihydroxybenzoic acid. The reaction was not affected by superoxide dismutase, catalase or aspirin. These findings and preliminary studies of the Fe++ induced oxidation product of AA as a substrate for prostaglandin synthesis and inhibitor of prostacyclin production indicate the critical role of Fe++ in AA activation.

Antimetabolites↗

PubMed2004

Synthesis of a glucuronic acid and glucose conjugate library and evaluation of effects on endothelial cell growth.

Compounds that alter endothelial cell growth are of interest in the development of angiogenesis modulators. A structurally diverse series of saccharide derivatives (glycosylamide conjugates) have been synthesized and evaluated for their effects on bovine aortic endothelial cell (BAEC) growth. Heparin-albumin (HA) reduced BAEC growth by 32% at 10 microg/mL and a number of the novel saccharide conjugates from the library were found to mimic the effect of HA as they also inhibit endothelial cell survival under identical conditions. Two thiophene conjugates, thioglucamide (24% inhibition at 35 microM) and a related glucuronide (26% inhibition at 33 microM) were the most potent inhibitors of BAEC growth, as determined using a methylthiazol tetrazolium (MTT) assay. The effects of thioglucamide and HA on absolute cell number were also studied using cell counting experiments; thioglucamide (47% after 24 h) was more potent than indicated by the MTT assay and initially reduced the BAEC number to a greater extent than HA (30% after 24 h); however, its actions were over more rapidly than were HA's as cell growth had returned to levels of the control after 72 h where HA still caused 25% inhibition. The binding of the monosaccharide conjugates to fibroblast growth factor (FGF-2) in competition with heparin-albumin by ELISA was investigated to establish the possible mechanism by which glycoconjugates could alter growth but there was no general correlation between reduction in viable cell population and binding to FGF-2. No glycoconjugate reduced the proliferation of mouse mammary epithelial cells, nor did any alter gross cell morphology, supporting a proposal that the reduction in BAEC survival by monosaccharide conjugates such as thioglucamide is a result of the inhibition of cell proliferation rather than being an induction of cytotoxicity. These studies indicate that cell biological studies to determine the mechanism of action of the simple monosaccharide conjugates may be worthwhile.

Animals↗