Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed an improved and reliable method for stereoselective functionalization at C4 of naturally occurring (+)-catechin. Our method utilizes DDQ oxidation followed by trapping of the quinonemethide intermediate with allyl alcohol. The quinonemethide intermediate can be regenerated from the allyl ether by exposure to boron trifluoride diethyl etherate. This reactive intermediate can be trapped with a wide range of external nucleophiles. NBS bromination, lithium halogen exchange, and alkylation gave access to C8-allyl derivatives of (+)-catechin, and this allyl group was used in a series of cross-metathesis experiments to prepare novel dimeric catechin-derived products. Gallate ester derivatives of the novel C4- and C8-substituted catechins were prepared, and these materials were screened for potential anticancer activity in a range of human cancer cell lines. From these preliminary cytotoxicity assays (MTT) we found that C8-propyl-catechin gallate was more active (IC50 = 31 microM) than catechin gallate (CG, IC50 = 53 microM) or epicatechin gallate (ECG, IC50 = 76 microM) against the colorectal adenocarcinoma cell line HCT116. Differential sensitivity in pancreas (Pan1), bladder (RT112), stomach (MGLVA1), liver (HepG2), and fibroblasts (46Br.1G1) cell lines was also observed.
 ...
PMID:Synthesis and preliminary anticancer activity studies of C4 and C8-modified derivatives of catechin gallate (CG) and epicatechin gallate (ECG). 1716 88

Previous studies showed that cocaine exposure decreased brain-derived neurotrophic factor (BDNF) function and resulted in neuronal cell death. To investigate a role of BDNF in cocaine's cytotoxicity, an RNA interference (RNAi) approach was used. Transfection of neuroblastoma SK-N-AS cells or primary rat hippocampal neurons with the small double-stranded interfering RNA (siRNA) targeting BDNF mRNA, but not the scrambled siRNA, resulted in reductions in levels of BDNF mRNA and proteins by more than 70% in the transfected cells as compared with the control group, suggesting an RNAi-mediated, sequence-specific gene silencing. The results also showed that cocaine-induced cytotoxicity, assessed by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazodium bromide) assay, was more pronounced in the cells transfected with the siRNA than in the cells transfected with the scrambled siRNA or in the cells treated with Lipofectamine 2000 alone (the control group), suggesting that inhibition of BDNF expression enhances cocaine's cytotoxicity. Together with previous studies showing that cocaine suppresses BDNF expression, the present data suggest that the drug-induced reduction of BDNF productions may make neurons more vulnerable to cocaine's toxic effects and precipitate cocaine-induced central nervous system damages.
 ...
PMID:RNA interference-mediated inhibition of brain-derived neurotrophic factor expression increases cocaine's cytotoxicity in cultured cells. 1719 38

The potential cytotoxicity of two hexanedione food additives (2,3 and 3,4 isomers) was evaluated in comparison with the neurotoxic hexane metabolite 2,5-hexanedione in the human SK-N-SH neuroblastoma line using the MTT assay to indicate mitochondrial dehydrogenase activity and flow cytometry to monitor the cell cycle over 48 h. The IC(50)s of the 2,3-hexanedione (3.3+/-0.1 mM) and 3,4-hexanedione (3.5+/-0.1 mM), indicated that the sensitivity of the cells was approximately seven-fold greater to these toxins compared with the 2,5 derivative (IC(50) of 22.4+/-0.2 mM). Comparison between the respective IC(50)s of the 2,3-hexanedione and 3,4-hexanedione revealed no difference between the two isomers in terms of their effects on MTT turnover. With flow cytometry analysis, all three hexanediones showed increases in apoptosis within their respective concentration ranges of toxicity shown previously by MTT. In the presence of 2,5-hexanedione, between 8.5 and 17 mM concentrations, there was a significant increase in apoptotic nucleoids which was accompanied by a significant fall in the percentage of nucleoids in the G0/G1 phase (72.4+/-0.3-45.3+/-0.6%,), and a rise in the numbers of cells in the G2/M phase. This is likely to indicate growth arrest at cell cycle G2/M checkpoint in response to toxin damage. G2/M accumulation was also shown with 3,4 and 2,3 HD, which was maximal at much lower concentrations (approximately 4 and 3mM, respectively). Arrest at G1 and G2/M phase is indicative of inhibition of the cell cycle at the stages of DNA replication and chromosome segregation, respectively. It was also apparent that flow cytometry, rather than the MTT assay, did distinguish between the effects of the alpha-diketones 2,3-hexanedione and 3,4-hexanedione on the cell cycle. At a concentration of 5.8mM 3,4-hexanedione, the percentage of apoptotic nucleoids was 10.9+/-0.8% whilst apoptosis induced by 3,4-hexanedione had already reached a maximal level of 60.4+/-0.5%. In summary, flow cytometry indicated that the 3,4-hexanedione derivative was more toxic than its 2,3 isomer and that both food additives caused interruption in the neuroblastoma cell cycle and further investigation may be required to assess if these alpha-diketones present in diets pose any possible risks to human health.
 ...
PMID:Apoptotic and necrotic effects of hexanedione derivatives on the human neuroblastoma line SK-N-SH. 1722 11

The origin of malignant embryonal tumors is incompletely understood and certain risk groups remain difficult to treat. The epigenetic structure of DNA and its lesions play a role in the origin of these neoplasms. Manipulation of the epigenome may offer novel treatment options. The authors evaluated the cytotoxicity of histone deacetylase inhibitors (HDI) [MS-275, SAHA, TSA, M344, M360, D85, SW55, SW187 and valproic acid (VPA)] on 13 embryonal tumor cell lines [4 medulloblastomas, 5 neuroblastomas, 2 atypical teratoid/rhabdoid tumors (AT/RT), and 2 malignant rhabdoid tumors of the kidney (RTK)] in MTT assay. In addition, HDI effects on hyperacetylation, reexpression of growth regulatory genes and apoptosis were characterized by Western analysis, RT-PCR and annexin-V staining. All HDI inhibited cell proliferation in a time- and dose-dependent manner. VPA was least cytotoxic with GI50 values after 72 hr ranging from 53.6 to 332.9 microM, while TSA was most efficient with GI50 values after 72 hr ranging from 0.01 to 8.8 microM. M344 and M360 were also highly effective. Western blot revealed hyperacetylation of histone H4 after HDI treatment. Reactivation of several genes including the proapoptotic CASP8 was identified by RT-PCR. Annexin-V staining demonstrated a dose and time dependent induction of apoptosis. HDI inhibited the growth of medulloblastoma, neuroblastoma and rhabdoid tumors in vitro. Treatment with HDI induced the reactivation of growth regulatory genes and consequently apoptosis. Our results warrant further studies and may help in the design of new protocols geared at the treatment of high risk embryonal tumors.
 ...
PMID:Inhibitors of histone deacetylases as potential therapeutic tools for high-risk embryonal tumors of the nervous system of childhood. 1723 May 17

We have previously defined a homozygously deleted region at chromosome 1p36.2-p36.3 in human neuroblastoma cell lines, NB-1 and NB-C201, and identified six genes including DFF45/ICAD within this region. In this study, we found that NB-C201 cells are much more resistant to various genotoxic stresses such as cisplatin (CDDP) than CHP134 and SH-SY5Y cells that do not have the homozygous deletion. To examine a role(s) of DFF45 in the regulation of apoptosis in response to CDDP, we have established stably DFF45-expressing NB-C201 cell clones (DFF45-1 and DFF45-3) and a control cell clone (NB-C201-C) using a retrovirus-mediated gene transfer. In contrast to NB-C201-C cells, DFF45-3 cells displayed apoptotic nuclear fragmentation in response to CDDP. Although CDDP-induced proteolytic cleavage of procaspase-3 and DFF45 in DFF45-3 cells, we could not detect a typical apoptotic DNA fragmentation. Additionally, deletion analysis revealed that C-terminal region of DFF45 is required for inducing nuclear fragmentation. Unexpectedly, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays demonstrated that DFF45 has undetectable effect on CDDP sensitivity of NB-C201 cells. Taken together, our present results suggest that DFF45/DFF40 system may be sufficient for CDDP-induced nuclear fragmentation but not DNA cleavage.
 ...
PMID:DFF45/ICAD restores cisplatin-induced nuclear fragmentation but not DNA cleavage in DFF45-deficient neuroblastoma cells. 1735 5

Novel trinuclear complexes C23H31N6O6CuSn2Cl5 [1], C23H31N6O6CuZr2Cl5 [2], C23H31N6O6ZnSn2Cl5 [3], and C23H31N6O6ZnZr2Cl5 [4] were synthesized and characterized by spectroscopic (IR, 1H, 13C, 2D COSY, and 119Sn NMR, EPR, UV-vis, ESI-MS) and analytical methods. In complexes 1-4, the geometry of copper and zinc metal ions were described as square-based pyramidal with l-tryptophan coordinated to copper/zinc via carboxylate group while Sn/Zr was present in the hexacoordinate environment. The interaction of 1 and 2 with calf thymus DNA in Tris buffer was studied by electronic absorption titration, luminescence titration, cyclic voltammetry, circular dichroism, and viscometric measurements. The emission quenching of these complexes by [Fe(CN)6]4- depressed greatly when bound to DNA. Observed changes in the circular dichoric spectra of DNA in presence of 1 and 2 support the strong binding of complexes with DNA. The relative specific viscosity of DNA bound to 1 and 2 decreased, indicating that the complexes bind to DNA via covalent binding. The results reveal that the extent of DNA binding of 1 was greater than that of 2. To evaluate the mechanistic pathway of DNA inhibition, counting experiments and MTT assay were employed to assess the induction of apoptosis by 1. Western blot analysis of whole cell lysates and mitochondrial fractions with Bcl-2 and p-53 family proteins and caspase-3 colorimetry assay were also carried out on a human neuroblastoma cell line SY5Y.
 ...
PMID:DNA binding studies of novel Copper(II) complexes containing L-tryptophan as chiral auxiliary: in vitro antitumor activity of Cu-Sn2 complex in human neuroblastoma cells. 1737 49

Cytoglobin (Cygb) is a recently discovered intracellular respiratory globin, which exists in all types of cells. It has been suggested that Cygb has a role in protecting cells against oxidative stress. In the present study we have tested this hypothesis. The N2a neuroblastoma cells were exposed to various kinds of insults, including hydrogen peroxide (H(2)O(2)), hypoxia, kainic acid, high extracellular CaCl(2), high osmolarity, UV irradiation and heat shock. Among them, only H(2)O(2)-treatment induced a significant up-regulation of cytoglobin mRNA level. We stably transfected N2a cells with Cygb-siRNA vectors and successfully knocked down Cygb. The Cygb-siRNA could exacerbate cell death upon H(2)O(2)-treatment, as demonstrated by MTT cell viability assay. Thus, Cygb in neuronal cells might be specifically induced under oxidative stress to protect them from death.
 ...
PMID:Cytoglobin up-regulated by hydrogen peroxide plays a protective role in oxidative stress. 1747 93

In order to examine the neuroprotective effects of the alpha7 nicotinic receptor (nAChR) in relationship to the pathogenesis of Alzheimer's disease (AD), neuroblastoma (SH-SY5Y) cells were transfected with small interference RNAs (siRNAs) that targets specifically towards alpha7 nAChR or exposed to 20microM 3-[2,4-dimethoxybenzylidene] anabaseine (DMXB), a selective agonist of this same receptor. The levels of alpha7 nAChR mRNA and protein were measured by RT-PCR and Western blotting, respectively. The levels of the alpha-form of secreted amyloid precursor protein (alphaAPPs), total APP and the extracellular signal-regulated kinase 1/2 (ERK1/2) were also determined by Western blotting. SH-SY5Y cells transfected with siRNA or exposed to DMXB were then treated with 1microM Abeta(25-35), following which the levels of lipid peroxidation and rate of reduction of MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] were characterized by utilizing spectrophotometric procedures. Compared to controls, SH-SY5Y cells transfected with siRNA expressed the decreases in the levels of alpha7 nAChR mRNA and protein by 81% and 69% lower levels, respectively; exhibited reduced levels of the alphaAPPs and ERK1/2 proteins; and demonstrated enhanced lipid peroxidation and a decreased rate of MTT reduction. In cells exposed to DMXB, the level of alpha7 nAChR protein was elevated by 23%, with no alteration in the content of the corresponding mRNA; the levels of the alphaAPPs and ERK1/2 proteins were increased. Inhibition of the expression of the alpha7 nAChR gene enhanced the toxicity exerted by Abeta, whereas stimulation of this receptor attenuated this toxicity exerted. These findings indicate that alpha7 nAChR may play a significant neuroprotective role by enhancing cleavage of APP by alpha-secretase, regulating signal transduction, improving antioxidant defenses and inhibiting the toxicity of Abeta, which is connected with the pathogenesis of AD.
 ...
PMID:The consequences of reducing expression of the alpha7 nicotinic receptor by RNA interference and of stimulating its activity with an alpha7 agonist in SH-SY5Y cells indicate that this receptor plays a neuroprotective role in connection with the pathogenesis of Alzheimer's disease. 1749 9

The aim of the present study is to investigate the effect of genistein on human neuroblastoma SK-N-MC cells. MTT proliferation assay, LDH cytotoxicity assay, flow cytometric analysis, real-time quantitative RT-PCR and western blotting were used to investigate the effect of genistein on cell survival, cellular toxicity, cell cycle progression, and mRNA and protein alterations of selected DNA damage-, cell cycle- and apoptosis-related genes in SK-N-MC cells. Genistein suppressed cell proliferation, increased LDH release and modulated cell cycle distribution through accumulation of cells at G2/M- and S-phase and sub-G0 (cell death) with a concurrent decrease of cells at G0/G1 phase. Genistein increased the MDC1 (Mediator of DNA damage Checkpoint protein 1), p53, p21(waf1/cip1), Cdc2 and Bax mRNA levels in a dose-dependent manner. However, PLK1 (Polo-Like Kinase 1) and Cyclin B1 mRNAs were down-regulated after genistein treatment. Furthermore, Genistein did not alter Chk2 (Checkpoint Kinase 2), Bcl-2 and Cdc25C mRNA levels. On western blotting analyses; genistein increased the protein level of MDC1, p53, p21(waf1/cip1), and Bax in a dose-dependent manner. Genistein also increased the phosphorylation of Chk2 and Cdc25C at Thr-68 and Ser-216, respectively. In addition, consistently with PLK1 down-regulation, the phosphorylation of Cdc25C at Ser-198 was markedly decreased after genistein treatment. Additionally, Chk2, Cdc25C, Cyclin B1, p-Cyclin B1 (Ser-147), and Cdc2 as well as Bcl-2 proteins were down-regulated after genistein treatment. Altogether, these results suggest for the first time the involvement of MDC1 up-regulation after genistein treatment in DNA damage-induced Chk2 activation- and PLK1 down-regulation-mediated apoptosis and cell cycle checkpoint pathways.
 ...
PMID:Genistein-induced neuronal apoptosis and G2/M cell cycle arrest is associated with MDC1 up-regulation and PLK1 down-regulation. 1770 63

Cell viability studies are useful when screening novel drugs for the diseases that are related to either increased cell death or enhanced cell survival. There are numerous assays but the results that they produce are rarely unanimous. Here we compared the performance of (1) morphological microscopic assay with double DNA staining, (2) propidium iodide-digitonin assay, (3) MTT-assay, and (4) ATP-assay in human neuroblastoma (SH-SY5Y), rat glioma (C6), rabbit smooth muscle (SMC), Chinese hamster ovary (CHO) and monkey fibroblast cells (CV1-P) exposed to cytosine arabinoside (Ara-C) and 6-hydroxydopamine (6-OHDA). We found that neuronal SH-SY5Y cells were most sensitive to both toxins and the results in all viability tests correlated well. All the other cell lines were much more resistant, particularly to Ara-C but also to 6-OHDA. Toxicity of the compounds was best revealed by MTT and ATP assays, measuring the metabolic activity of the cells, and only occasionally by morphological observations or with the propidium iodide-digitonin assay which is based on the cell membrane integrity. In this research, Ara-C induced pure apoptosis whereas the toxicity type of 6-OHDA was dose-dependent. The use of several viability tests and cell lines is recommended when studying cell death, particularly apoptosis, and performance of antiapoptotic compounds.
 ...
PMID:Different viabilities and toxicity types after 6-OHDA and Ara-C exposure evaluated by four assays in five cell lines. 1776 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>