Resistance to induced apoptosis in the human neuroblastoma cell line SK‐N‐SH in relation to neuronal differentiation

Lombet, Alain; Zujovic, Violetta; Kandouz, Mustapha; Billardon, C; Carvajal‐Gonzalez, Santos; Gompel, Anne; Rostène, William

doi:10.1046/j.1432-1327.2001.02002.x

Cited by 60 publications

(59 citation statements)

References 48 publications

(50 reference statements)

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“…Antiapoptotic Bcl-2 is one of the most important members that inhibits the mitochondria-dependent apoptotic pathway triggered by diverse cytotoxic agents through blocking mitochondrial permeability transition. Indeed, the upregulation of Bcl-2 was associated with the drug-resistant phenotype of certain human tumors (Dole et al, 1994;Lombet et al, 2001). Most intriguingly, our expression studies revealed that antiapoptotic Bcl-2 was constitutively overexpressed in LA-N-5 and RTBM1 cells, whereas its expression levels were extremely low in CHP134 and NB-39-nu cells.…”

Section: Discussionmentioning

confidence: 60%

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma

et al. 2006

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Section: Discussionmentioning

confidence: 60%

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma

et al. 2006

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“…In line with these results, a substantial reduction of cell viability was found in an LDH release assay, suggesting that over-expression of CADM1 in human neuroblastoma cell lines does not only reduce proliferation, but might also function as a proapoptotic or pronecrotic regulator. CADM1 over-expression is known to induce apoptosis in A549 non-small cell lung cancer cells (Mao et al, 2004), but many human neuroblastoma cell lines show considerable resistance to apoptosis when exposed to common apoptosis inducing triggers (Teitz et al, 2000;Lombet et al, 2001). Therefore, further experiments are necessary to more precisely delineate the mechanisms by which CADM1 triggers changes in growth properties and loss of cell viability.…”

Section: Discussionmentioning

confidence: 99%

Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma

et al. 2007

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“…17,18 Bax expression is not significantly modified. 15 Therefore, although both MPA and retinoic acid induce similar morphologic differentiation in neuroblastoma cells, the molecular mechanisms involved appear to be different. In conclusion, MPA, at concentrations corresponding to those of the active free drug readily attainable therapeutically using mycophenolate mofetil, induces neuroblastoma cells to differentiate toward the neuronal phenotype, confirming a potential role of CellCept in the management of neuroblastoma patients.…”

Section: Dear Sirmentioning

confidence: 99%

Low levels of mycophenolic acid induce differentiation of human neuroblastoma cell lines

Messina

Gazzaniga

Micheli

et al. 2004

Intl Journal of Cancer

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Dear Sir,In a previous report, 1 we showed that mycophenolic acid (MPA), at concentrations readily attainable during immunosuppressive therapy (0.1-10 M), using its mycophenolate mofetil prodrug, causes a decrease of intracellular levels of guanine nucleotides, G 1 arrest and time-and dose-dependent death by apoptosis. The first effect appears to be the consequence of inosine monophosphate dehydrogenase (IMPDH) inhibition and to trigger the other effects through p53-mediated pathways.MPA fails to achieve high concentrations following in vivo administration because of rapid glucuronidation, which inactivates the drug. 2 The morpholinoethyl ester of MPA (mycophenolate mofetil; CellCept, Roche, Milan, Italy) has improved bioavailability and is used as an immunosuppressant following solid-organ transplants. 2 Mycophenolate mofetil is rapidly absorbed following oral administration and almost completely hydrolyzed to the active metabolite MPA, which is extensively and tightly bound to human albumin. [2][3][4] Free MPA in most patients accounts for about 2% of the mean plasma drug level, which is usually maintained around 3 g/ml. 4 We previously reported apoptotic effects on human neuroblastoma cell lines obtained at MPA concentrations corresponding to the total plasma drug levels during immunosuppressive CellCept therapy. 1 In the present study, we investigated the effects of this drug on human neuroblastoma cell lines at lower concentrations, corresponding to those of the active free drug readily attainable during therapy with mycophenolate mofetil.Three established human neuroblastoma cell lines (LAN5, IMR32 and SK-N-SH) were utilized in the current study. Exponentially growing cells were cultured at 37°C in a humidified atmosphere with 5% CO 2 in RPMI-1640 supplemented with 10% FBS, 100 units/ml penicillin, 100 g/ml streptomycin and 2 mM glutamine. Cells were treated with 50 nM MPA or not in the presence or absence of 0.1 mM guanosine for 3 and 6 days. Incubation media were changed every 3 days. Addition of 50 nM MPA led to a decrease of intracellular guanine nucleotide levels with respect to control cells cultured in the absence of drug after 3 or 6 days of incubation. In LAN5 cells, nucleotide extraction and chromatographic analysis performed as described 1 evidenced a guanine nucleotide depletion (87% of GTP, 77% of GDP control values) after 3 days of incubation in the presence of drug. This effect was reversed, at least in part, by 0.1 mM guanosine, added simultaneously with the IMPDH inhibitor: after 6 days of incubation in the presence of guanosine, the reduction of guanine nucleotide levels with respect to control cells was less evident (GTP 92%, GDP 83% of control values).After 6 days of incubation in the presence of 50 nM MPA, neuroblastoma cells differentiated toward the neuronal phenotype with outgrowth of neurite-like processes. In IMR32 cells, the morphologic changes were less evident. Immunofluorescence or immunoperoxidase analysis using anti-NF200 (intermediate filaments), anti-GAP43 (growth-associat...

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Resistance to induced apoptosis in the human neuroblastoma cell line SK‐N‐SH in relation to neuronal differentiation

Cited by 60 publications

References 48 publications

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma

Bcl-2 is a key regulator for the retinoic acid-induced apoptotic cell death in neuroblastoma

Expression of the tumour suppressor gene CADM1 is associated with favourable outcome and inhibits cell survival in neuroblastoma

Low levels of mycophenolic acid induce differentiation of human neuroblastoma cell lines

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