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

D-Alpha-tocopheryl succinate (vitamin E succinate) at a concentration of 11.3 microM inhibited growth and reduced the expression of c-myc, N-myc and H-ras specific mRNAs in murine neuroblastoma cells (NBP2) in culture. R020-1724 [4-(3-butoxy-4-methoxybenzyl)-2- imidazolidinone], an inhibitor of cyclic AMP phosphodiesterase, also inhibited growth and reduced the expression of these oncogenes. Vitamin E succinate treatment caused the formation of two c-myc related transcript of 1.9 and 3.7 kb; however, R020-1724 treatment did not. These results suggest that the inhibition of growth is sufficient to reduce the expression of c-myc, N-myc and H-ras in NB cells in culture, but it is not sufficient to produce two c-myc related transcripts.
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PMID:Effect of vitamin E succinate and a cAMP-stimulating agent on the expression of c-myc and N-myc and H-ras in murine neuroblastoma cells. 164 46

Effects of local anesthetics and anticonvulsants on the pyrethroid-modified sodium current in cultured mouse neuroblastoma cells have been investigated using the suction pipette voltage clamp technique. In the presence of 10 microM of the pyrethroid deltamethrin the sodium current consists of an enhanced peak current during membrane depolarization and a slowly decaying, deltamethrin-induced tail current remaining after repolarization. At the onset of block the local anesthetics tetracaine, lidocaine and QX 314 reduced the deltamethrin-induced tail current more effectively than the peak current. Lidocaine, but not phenytoin, caused a time-dependent block of tail currents evoked by membrane depolarizations lasting 10-1000 ms. Both lidocaine- and phenytoin-induced blocks were independent of the membrane potential during the tail current. The anticonvulsants phenytoin, phenobarbital and valproate blocked the tail and the peak sodium current to the same extent, but diazepam, mephenesin and urethane blocked the peak current more effectively. Vitamin E, which suppresses pyrethroid-induced paresthesia of the skin, had no effect on the voltage-dependent sodium current. It is concluded that indirect effects of anticonvulsants on pyrethroid-induced toxic symptoms predominate, whereas local anesthetics preferentially block the pyrethroid-induced tail current. Therefore, local anesthetics are potentially useful pyrethroid antidotes.
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PMID:Block of deltamethrin-modified sodium current in cultured mouse neuroblastoma cells: local anesthetics as potential antidotes. 216 45

Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of two murine neuroblastomas (C1300, NS-20) was investigated in vivo. Five groups of mice were prepared; group 1 were fed the control diet, group 2 were fed a vitamin E-deficient diet, group 3 were fed a vitamin E-supplemented diet, group 4 were fed the control diet and plus vitamin E solution given intraperitoneally during the treatment (solvent i.p. group), and group 5 were given vitamin E in the same manner (20 mg/kg/day; vitamin E i.p. group). Cisplatin (6 mg/kg) was injected intraperitoneally into the mice of each group during the treatment. In case of the C1300 neuroblastoma, the antitumor activity of cisplatin was most enhanced in the mice receiving vitamin E i.p., and the intra-tumor vitamin E and platinum levels were significantly higher in this group than in the other groups (P less than 0.01, and P less than 0.05 respectively). In contrast, in animals transplanted with the NS-20 murine neuroblastoma, which proved to be a cisplatin-tolerant tumor in separate experiments, no combined effect of those drugs was observed, although the intra-tumor level of platinum was elevated. The possibility was that vitamin E increases the influx of cisplatin into the tumor cells and acts after incorporation of cisplatin through the plasma membrane. Vitamin E did not accentuate the cisplatin-induced renal impairment in vitamin E-loaded groups. Those results suggested that vitamin E should be considered as a co-agent of cisplatin for the treatment of neuroblastoma.
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PMID:Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of murine neuroblastoma in vivo. 320 17

Alpha tocopheryl succinate treatment (6-8 micrograms/ml), which inhibited the growth of murine neuroblastoma (NBP2) cells (46 +/- 3%), reduced basal and prostaglandin (PG)E1- and PGA2-stimulated adenylate cyclase (AC) activity in vitro. It also inhibited sodium fluoride (NaF)- and forskolin-stimulated AC activity, suggesting that the effect of vitamin E succinate on AC activity is mediated via stimulatory GTP-binding protein (Gs) and catalytic subunit. Vitamin E succinate-induced reduction of AC activity is not strictly related to inhibition of cell growth. This is substantiated by the finding that, although retinoic acid and butylated hydroxyanisole reduced the growth by over 50%, they did not inhibit AC activity. On the other hand, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone (R020-1724, 200 micrograms/ml), which inhibited growth (73 +/- 3%) and induced differentiation in NB cells, increased basal and PGE1-stimulated AC activity. Vitamin E succinate treatment also reduced PGE1- and PGA2-AC activity in murine fibroblasts (L-cells) without inhibiting growth.
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PMID:Effect of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture. 320 80

The effects of vitamin E (vit.E, d-alpha-tocopherol acid succinate) on the growth and the morphological differentiation of 4 representative murine neuroblastoma cell lines: C1300 (wild type), NS-20 (cholinergic type), N-18 (inactive type), N1E-115 (adrenergic type), and the combined effects of vit.E and cis-diamminedichloroplatinum(II)(cisplatin, CDDP) were studied in culture. Vitamin E inhibited the growth of all clonal cells in a dose-dependent manner, especially that of NS-20 cells, and it caused significant morphological differentiation only in NS-20 cells. In addition, vit.E enhanced the growth inhibition of C1300 cells by cisplatin in an additive manner, but not that of NS-20 cells. These suggested that both phenomena induced by vit.E may not always occur in parallel in each clonal neuroblastoma, and both mechanisms might be different.
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PMID:Different effects of vitamin E on the growth and morphological differentiation of 4 murine neuroblastoma cell lines in vitro. 323 50

The effect of dl-alpha-tocopheryl (vitamin E) succinate in combination with Prostaglandin A2 (PGA2) and sodium butyrate on mouse neuroblastoma cells (NBP2) in culture, according to the criteria of growth inhibition and morphological differentiation (neurite formation), was studied. Results showed that PGA2 and sodium butyrate inhibited the growth of NB cells in a dose-dependent manner. The combined effects of vitamin E succinate with PGA2 or sodium butyrate, according to the criterion of growth inhibition, were additive. Vitamin E succinate by itself did not induce morphological differentiation, but it enhanced PGA2-induced morphological differentiation. Sodium butyrate alone or in combination with vitamin E succinate did not significantly increase the level of morphological differentiation. Sodium succinate and an equal amount of solvent (ethanol) failed to modify the effect of PGA2 or sodium butyrate. This suggests that the effect of vitamin E succinate in modifying the response of PGA2 and sodium butyrate on NB cells is due to the effect of vitamin E rather than to that of succinate.
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PMID:Effects of dl-alpha-tocopheryl succinate in combination with sodium butyrate and cAMP stimulating agent on neuroblastoma cells in culture. 609 78

Neurotoxic effects of methylmercury, were investigated in vitro in primary cultures of human neurons and astrocytes isolatedfrom human fetal brain and in the human neuroblastoma cell line SH-SY5Y. The protection provided by agents with antioxidant properties was tested in these cultures to examine the oxidative stress mechanism of methylmercury poisoning. After 24 h of exposure to methylmercury, LC50 values were 6.5, 8.1 and 6.9 microM for human neurons, astrocytes and neuroblastoma cells, respectively, and the degree of cell damage increased at longer exposure times. Depletion of the cellular pool of reduced glutathione (GSH) by treatment with buthionine sulfoximine potentiated methylmercury cytotoxicity in all three cell types; neuroblastoma cells were the most sensitive. Addition of GSH extracellularly blocked methylmercury neurotoxicity in all cell types. The major beneficial effect of GSH could be attributed to its capacity to form conjugates with methylmercury, which reduces the availability of these organometallic molecules to the cells and facilitates their efflux. Cysteine protected astrocytes and neuroblastoma cells from methylmercury neurotoxicity, while selenite, Vitamin E and catalase produced some minor protective effects in three cell types, particularly in neurons. The present study showed that the human neural cells tested had differential responses to methylmercury: astrocytes were resistant to methylmercury neurotoxicity and neurons were more most responsive to protection afforded by antioxidants among the three cell types.
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PMID:Methylmercury neurotoxicity in cultures of human neurons, astrocytes, neuroblastoma cells. 1145 33

The neurotoxic effects and influence of beta-amyloid peptide (Abeta)(1-42) on membrane lipids and nicotinic acetylcholine receptors (nAChRs) in human SH-SY5Y neuroblastoma cells were investigated in parallel. Exposure of the cultured cells to varying concentrations of Abeta(1-42) evoked a significantly decrease in cellular reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyl tetrazolium bromide), together with enhanced lipid peroxidation and protein oxidation. Significant reductions in the total contents of phospholipid and ubiquinone-10, as well as in the levels of the alpha3 and alpha7 subunit proteins of nAChRs were detected in cells exposed to Abeta(1-42). In contrast, such treatment had no effect on the total cellular content of cholesterol. Among these alterations, increased lipid peroxidation and decreased levels of cellular phospholipids were most sensitive to Abeta(1-42), occurring at lower concentrations. In addition, when SH-SY5Y cells were pretreated with the antioxidant Vitamin E, prior to the addition of Abeta(1-42), these alterations in neurotoxicity, oxidative stress, composition of membrane lipids and expression of nAChRs were partially prevented. These findings suggest that stimulation of lipid peroxidation by Abeta may be involved in eliciting the alterations in membrane lipid composition and the reduced expression of nAChRs associated with the pathogenesis of AD.
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PMID:Oxidative stress induced by beta-amyloid peptide(1-42) is involved in the altered composition of cellular membrane lipids and the decreased expression of nicotinic receptors in human SH-SY5Y neuroblastoma cells. 1586 39

Vitamin E (VE) analogues, epitomized by alpha-tocopheryl succinate (alpha-TOS), are potent inducers of apoptosis and anti-cancer agents. Here, we tested their effect on the highly malignant N-type neuroblastoma (Nb) cells and their differentiated, neurone-like counterparts. Nb cells were highly susceptible to several VE analogues, while differentiated Nb cells were relatively resistant to alpha-TOS. The importance of caspase-9 rather than caspase-8, as judged by specific siRNAs studies, together with the loss of the inner mitochondrial potential, suggests that alpha-TOS triggers apoptosis in Nb cells via the mitochondrial pathway. Cultured Nb cells were sensitized to alpha-TOS by pre-treatment with Bcl-2, Bcl-xL or Mcl-1 siRNAs, while the malignant cell line was more resistant to the vitamin E analogue when Bax was knocked down. In contrast, overexpression of Bcl-2 in Nb cells rendered them more resistant to alpha-TOS-induced apoptosis. The resistance of differentiated Nb cells to alpha-TOS-mediated apoptosis occurred via two modes: first, by up-regulation of the anti-apoptotic Bcl-2 family proteins and second, by accumulation of decreased levels of reactive oxygen species when challenged with alpha-TOS. We conclude that alpha-TOS is highly selective in killing malignant brain cancer cells while relatively inert toward differentiated neuronal cells, and that vitamin E analogues may be novel therapeutics for the treatment of tumours such as neuroblastomas.
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PMID:Alpha-tocopheryl succinate selectively induces apoptosis in neuroblastoma cells: potential therapy of malignancies of the nervous system? 1600 65

Toxicity of the typical antipsychotic haloperidol (HAL) comprises an apoptotic component that we link to pro-apoptotic Bcl-XS in PC12 preneuronal and N2a neuroblastoma cells. The mitochondrial translocation of Bcl-XS and its interaction with the pore-forming voltage-dependent anion channel (VDAC) correlates with the redistribution of cytochrome c and the cleavage of Poly(ADP-ribose) polymerase. Haloperidol-induced apoptosis is mediated by the sigma2 (sigma2) receptor system and does not involve the expected antagonism of the dopamine D(2) receptor, nor is it influenced by Vitamin E- or p53/Bax-mediated events. Pathological relevance is demonstrated by the cytotoxic synergism between HAL and the Alzheimer disease-related peptide beta-amyloid(1-40), which correlates with Bcl-XS expression and its interaction with VDAC, and with cytosolic cytochrome c translocation. These data provide for a unique apoptotic mechanism that could underscore the clinical risks associated with HAL, particularly following chronic regimens or in the elderly.
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PMID:Haloperidol induces apoptosis via the sigma2 receptor system and Bcl-XS. 1646 15


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