Regulation of acetylcholinesterase activity by retinoic acid in a human neuroblastoma cell line

Sidell, Neil; Lucas, C.A.; Kreutzberg, Georg W.

doi:10.1016/0014-4827(84)90795-x

Cited by 41 publications

(28 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As seen in Figure 4, there was a significant increase in specific AChE activity in cultures treated with a combination of 4-CPA and RAG compared with those treated with either agent alone. As previously reported, the induced increase in AChE activity generally paralleled the extent and complexity of neurite formation in the LA-N-5 cultures (Sidell et al, 1984(Sidell et al, , 1995Wuarin et al, 1991).…”

Section: Acetylcholinesterase Activitysupporting

confidence: 86%

“…Specific acetylcholinesterase (AChE) activity was measured as a biochemical index of the relative state of differentiation of treated and control LA-N-5 cells (Sidell et al, 1984). To measure the AChE activity, cells were grown in six-well tissue culture plates for 5 days in the absence or presence of the indicated concentrations of RAG and/or 4-CPA, washed twice with isotonic saline and harvested by vigorous shaking of the culture flask.…”

Section: Acetylcholinesterasementioning

confidence: 99%

“…To measure the AChE activity, cells were grown in six-well tissue culture plates for 5 days in the absence or presence of the indicated concentrations of RAG and/or 4-CPA, washed twice with isotonic saline and harvested by vigorous shaking of the culture flask. After removal of saline, cells were frozen at À701C, thawed by adding ice-cold 10 mM sodium phosphate buffer (pH 7.4) containing 0.5% Triton X-100 (1.5 ml 10 À6 cells) and sonicated for 10 s. Acetylcholinesterase activity in samples of the homogenate was determined photometrically by following the hydrolysis of acetylthiocholine as previously described (Sidell et al, 1984). Protein concentrations were determined with a Sigma Bicinchoninic acid protein assay kit using BSA as the standard.…”

Section: Acetylcholinesterasementioning

confidence: 99%

See 2 more Smart Citations

In vitro and in vivo effects of easily administered, low-toxic retinoid and phenylacetate compounds on human neuroblastoma cells

et al. 2003

View full text Add to dashboard Cite

We have investigated the effects of the low-toxic retinoid, all-trans retinoyl b-glucuronide (RAG) alone and in combination with the phenylacetate (PA) derivative 4-chloro-phenylacetate (4-CPA) on the human neuroblastoma cell line, LA-N-5. In vitro studies demonstrated that RAG and 4-CPA treatments alone showed differentiation-inducing activity on LA-N-5 cells, with 4-CPA found to be about three-fold more potent than the PA parent compound in inducing morphologic differentiation and growth inhibition. As previously reported for retinoic acid (RA) and PA, RAG and 4-CPA were significantly more effective in their antiproliferative effects on the cells than either agent alone. Pharmacologic studies of 4-CPA in mice demonstrated that blood plasma levels reached peak concentrations 4 h after bolus administration of the compound and showed slow clearance characteristics with an apparent half-life of 4 -8 h. As opposed to PA, 4-CPA was found to be essentially odourless and readily consumed in drinking water, giving rise to steadystate blood plasma levels of 4-CPA in the near mM range. Continuous consumption of 4-CPA in this manner for up to 5 months demonstrated no apparent adverse effects on the mice. Long-term RAG-and/or 4-CPA-treatment of nude mice injected with LA-N-5 cells demonstrated that both compounds alone exhibit potent antitumour activity. Together, RAG plus 4-CPA was the most effective treatment for inhibiting established tumour growth. In contrast, 4-CPA alone was equally as effective as the combination for preventing tumour development. The potent in vivo antitumour effects of 4-CPA could not be accounted for by the known ability of PA compounds to induce expression of the RA nuclear receptor beta (RARb) suppressor gene. Taken together, these findings demonstrate the possibility that RAG and/or 4-CPA may serve as effective, less-toxic alternatives to 13-cis RA, which is presently being utilised for nb therapy.

show abstract

Section: Acetylcholinesterase Activitysupporting

confidence: 86%

Section: Acetylcholinesterasementioning

confidence: 99%

Section: Acetylcholinesterasementioning

confidence: 99%

See 1 more Smart Citation

In vitro and in vivo effects of easily administered, low-toxic retinoid and phenylacetate compounds on human neuroblastoma cells

et al. 2003

View full text Add to dashboard Cite

show abstract

“…Neuroblastoma cells are arrested at immature stages of sympathetic differentiation, impairing the normal development into neuronal/ganglionic and neuroendocrine chromaffin cell lineages. The extensive neurite outgrowth, the expression of NEFL, NEF3, NEFH, HNT, and GAP43, the decrease in CHGA expression, and the neurotransmitter profile (NPY and CHAT) strongly suggest that the surviving fraction of nutlin-3-treated NGP cells matures along a sympathetic cholinergic neuronal lineage, a phenomenon also reported on retinoic acid treatment of cultured neuroblastoma cells (43,44). In CLB-GA cells, nutlin-3 promoted a noncholinergic sympathetic neuronal differentiation, with an initial transient coexpression of sympathetic neuronal and neuroendocrine markers reminiscent of the mixed neuronal/neuroendocrine phenotype in some maturing neuroblastoma tumors (27).…”

Section: Discussionsupporting

confidence: 60%

Small-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma

et al. 2006

View full text Add to dashboard Cite

Circumvention of the p53 tumor suppressor barrier in neuroblastoma is rarely caused by TP53 mutation but might arise from inappropriately increased activity of its principal negative regulator MDM2. We show here that targeted disruption of the p53-MDM2 interaction by the small-molecule MDM2 antagonist nutlin-3 stabilizes p53 and selectively activates the p53 pathway in neuroblastoma cells with wildtype p53, resulting in a pronounced antiproliferative and cytotoxic effect through induction of G 1 cell cycle arrest and apoptosis. A nutlin-3 response was observed regardless of MYCN amplification status. Remarkably, surviving SK-N-SH cells adopted a senescence-like phenotype, whereas CLB-GA and NGP cells underwent neuronal differentiation. p53 dependence of these alternative outcomes of nutlin-3 treatment was evidenced by abrogation of the effects when p53 was knocked down by lentiviral-mediated short hairpin RNA interference. The diversity of cellular responses reveals pleiotropic mechanisms of nutlins to disable neuroblastoma cells and exemplifies the feasibility of exploiting, by a single targeted intervention, the multiplicity of anticancer activities exerted by a key tumor suppressor as p53. The observed treatment effects without the need of imposing a genotoxic burden suggest that selective MDM2 antagonists might be beneficial for treatment of neuroblastoma patients with and without MYCN amplification.

show abstract

“…IMR-32 [20][21][22][23][24], SMS-KCN [22,25], and SMS-KAN [9,22,25,26] were established from an untreated primary tumor at the time of first diagnosis. In contrast, LAN-1 [22,24,27,28], LAN-5 [29][30][31], SK-N-SH [20,22-24, 32,33], SMS-KCNR [22,25], and SMS-KCNR [22,25] were derived from the bone marrow of patients whose disease had progressed despite prior treatment. Two sets of paired cell lines, SMS-KCN and SMS-KCNR, and SMS-KAN and SMS-KANR were each established from a single patient, from the primary tumor at diagnosis and the bone marrow at relapse, respectively [25].…”

Section: Resultsmentioning

confidence: 99%

Low complex ganglioside expression characterizes human neuroblastoma cell lines

2005

View full text Add to dashboard Cite

Low (≤35%) or absent expression of the complex 'b' pathway gangliosides GD1b, GT1b and GQ1b (CbG) correlates with an aggressive biological phenotype in human neuroblastoma tumors. To develop an in vitro model to probe mechanisms by which CbG may contribute to neuroblastoma behavior, we have comprehensively evaluated ganglioside expression in nine well-established human neuroblastoma cell lines, all derived from poor prognosis tumors. Total cellular ganglioside content ranged from 8 to 69 nmol/10 8 cells. High performance thin layer chromatography revealed that the simple disialoganglioside GD2 was prominent in eight of the cell lines (up to 60% of total gangliosides), whereas CbG were low (1-21%) in all nine cell lines. The structurally most complex 'b' pathway species, GQ1b, was not detected in any of the cell lines. The prominence of GD2 in neuroblastoma cell lines mirrors the high expression of GD2 that characterizes human neuroblastoma tumors, and the low CbG expression in the cell lines is analogous to that found in clinically and biologically unfavorable neuroblastoma tumors, thus establishing these neuroblastoma cell lines as valuable model systems for study of the role of CbG in the pathobiology of human neuroblastoma.

show abstract

Regulation of acetylcholinesterase activity by retinoic acid in a human neuroblastoma cell line

Cited by 41 publications

References 14 publications

In vitro and in vivo effects of easily administered, low-toxic retinoid and phenylacetate compounds on human neuroblastoma cells

In vitro and in vivo effects of easily administered, low-toxic retinoid and phenylacetate compounds on human neuroblastoma cells

Small-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma

Low complex ganglioside expression characterizes human neuroblastoma cell lines

Contact Info

Product

Resources

About