Implication of glucocorticoid receptors in the stimulation of human glioma cell proliferation by dexamethasone

Langeveld, Cornelis H.; Waas, M. P. Van; Stoof, Johannes C.; Sutanto, W.; Kloet, E. Ronald de; Wolbers, J.G.; Heimans, Jan J.

doi:10.1002/jnr.490310316

Cited by 38 publications

(34 citation statements)

References 30 publications

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“…On the contrary, lower DEX concentrations (1.6 to 1000 nM), resembling more plasma levels of patients receiving antiemetic GC therapy, 27 increased the proliferation of GR-positive but not of -negative cells. 28 Langeveld et al 29 investigated the effect of DEX on the proliferation of seven human glioma cell lines. In two of them DEX consistently stimulated the proliferation which may be associated with a relatively high expression level of GR.…”

Section: The Effect Of Gcs Is Dependent On Gr Levelsmentioning

confidence: 99%

“…Although cytotoxicity of GCs has been demonstrated in some cell culture systems, 36,37 this effect may be negligible and be due to the use of steroid concentrations exceeding the pharmacological levels found in patients. Where more physiological concentrations have been used, both stimulation of cell proliferation 26,29,38 and inhibition have been observed in cultures of human tumor cells. 30,[39][40][41] In most cases, DEX significantly inhibited growth at high concentrations but stimulated growth at low concentrations.…”

Section: Effect Of Gcs On Cell Proliferation and Cell Cycle Progressionmentioning

confidence: 99%

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Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Mattern¹,

Büchler²,

Herr³

2007

Cancer Biology & Therapy

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ABBrevIAtIons DEX ABstrActGlucocorticoids have been widely used as cotreatment for patients with cancer due to potent pro-apoptotic properties in lymphoid cells, reduction of nausea and diminishing acute toxicity on normal tissue. There are now data from preclinical and, to some extent, clinical studies, demonstrating that these medicaments are highly suspicious to induce therapy resistance in the majority of malignant solid tumors-irrespective of tumor origin and the nature of specific anticancer drugs or irradiation used for treatment. Despite these huge amounts of data, the underlying mechanisms of cell type-specific signaling by these steroid hormones are just beginning to be described. This review summarizes our present understanding of a relationship between glucocorticoid-induced reversible cell cycle arrest and therapy resistance in solid tumors. We give a summary of our current knowledge of decreased proliferation rates in response to glucocorticoid pre and combination treatment which are suspicious to be involved not only in protection of normal tissues, but also in protection of solid tumors from cytotoxic effects of anticancer agents. The inhibition of cell cycle progression by pretreatment with GCs may be crucially involved in switching the balance of several interacting pathways to survival upon treatment with GCs.

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Section: The Effect Of Gcs Is Dependent On Gr Levelsmentioning

confidence: 99%

Section: Effect Of Gcs On Cell Proliferation and Cell Cycle Progressionmentioning

confidence: 99%

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Mattern¹,

Büchler²,

Herr³

2007

Cancer Biology & Therapy

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“…To determine cell survival, we used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as described previously (Langeveld et al, 1992) with some adaptations. An MTT stock solution was prepared and stored at Ϫ20ЊC.…”

Section: Methodsmentioning

confidence: 99%

“…To control for possible "nonspecific," non-DA-related drug effects on cellular GSH metabolism, human D384 glioma cells (Langeveld et al, 1992), not containing any detectable DA, were cultured in DMEM/F-10 containing 10% FCS and exposed to either reserpine or ␣MPT in the concentrations used for the experiments with PC12 cells. Incubation of the cells for up to 24 hr with either of the drugs did not induce any significant changes in cellular GSH content (data not shown).…”

Section: Effect Of ␣Mpt On Gsh Contentmentioning

confidence: 99%

Glutathione Is Involved in the Granular Storage of Dopamine in Rat PC12 Pheochromocytoma Cells: Implications for the Pathogenesis of Parkinson’s Disease

Drukarch¹,

Jongenelen²,

Schepens³

et al. 1996

J. Neurosci.

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Parkinson's disease (PD) is characterized by degeneration of dopamine (DA)-containing nigro-striatal neurons. Loss of the antioxidant glutathione (GSH) has been implicated in the pathogenesis of PD. Previously, we showed that the oxidant hydrogen peroxide inhibits vesicular uptake of DA in nigro-striatal neurons. Hydrogen peroxide is scavenged by GSH and, therefore, we investigated a possible link between the process of vesicular storage of DA and GSH metabolism. For this purpose, we used rat pheochromocytoma-derived PC12 cells, a model system applied extensively for studying monoamine storage mechanisms. We show that depletion of endogenous DA stores with reserpine was accompanied in PC12 cells by a longlasting, significant increase in GSH content the extent of which appeared to be inversely related to the rate of GSH synthesis. A similar increase in GSH content was observed after depletion of DA stores with the tyrosine hydroxylase inhibitor ␣-methylp-tyrosine. In the presence of ␣-methyl-p-tyrosine, refilling of the DA stores by exogenous DA reduced GSH content back to control level. Lowering of PC12 GSH content, via blockade of its synthesis with buthionine sulfoximine, however, led to a significantly decreased accumulation of exogenous [ 3 H]DA without affecting uptake of the acetylcholine precursor [ 14 C]choline. These data suggest that GSH is involved in the granular storage of DA in PC12 cells and that, considering the molecular characteristics of the granular transport system, it is likely that GSH is used to protect susceptible parts of this system against (possibly DA-induced) oxidative damage. Key words: Parkinson's disease; oxidative stress; glutathione; dopamine; PC12 cells; neurotransmitter uptake; vesicular storageParkinson's disease (PD) is characterized primarily by a loss of dopamine (DA) in the striatum caused by degeneration of DAergic neurons in the zona compacta of the substantia nigra (SN) (Gibb and Lees, 1991). Although the cause of PD is still unknown, oxidative stress has been implicated as a pathogenetic factor. According to this so called "free radical hypothesis," the degeneration of the nigro-striatal system in PD is related to the relatively high exposure of these neurons to reactive oxygen species (ROS), in particular hydrogen peroxide (H 2 O 2 ), produced during both the enzymatic (monoamine oxidase-catalyzed) and nonenzymatic (auto-oxidative) breakdown of DA (Adams and Odunze, 1991;Olanow, 1992). Thus, DAergic cell death in PD may be caused by an overproduction of ROS and/or a diminished protection against them. Evidence to support the "free radical hypothesis" has come from postmortem investigations of PD brains, which consistently show an increase in the indices of oxidative stress in the SN at the time of death (Hirsch et al., 1991;Jenner, 1993). One of these indices, possibly even preceding the loss of DA (Dexter et al., 1994), is a decrease in the level of glutathione (GSH) in the Parkinsonian SN (Riederer et al., 1989;Sofic et al., 1992;Jenner, 1993). GSH, the most abund...

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“…The proliferative activity of glucocorticoids on glioma cell lines has been studied for more than 30 years and both stimulatory [46,57,66,68,106] and inhibitory [30,44,57,59, 66] effects have been observed. A careful survey of these reports suggests that at least some of the discrepancies between studies result from the use of non-comparable experimental conditions, most notably regarding cell line type, cell culture density, glucocorticoid dose and culture medium (presence or absence of serum) ( Table 1).…”

Section: Glioma Cell Proliferation: In Vitro Studiesmentioning

confidence: 99%

Treating gliomas with glucocorticoids: from bedside to bench

et al. 2006

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Glucocorticoids are used in the treatment of gliomas to decrease tumour-associated oedema and to reduce the risk of acute encephalopathy associated with radiotherapy. However, the mechanisms by which glucocorticoids work are still largely unknown. In this paper, we survey the experimental and clinical evidence for the effects of glucocorticoids on tumour cell proliferation, apoptosis and sensitivity to chemotherapy, angiogenesis and vascular permeability. We then review current guidelines on the choice of molecule, dose and duration of glucocorticoid treatment for gliomas.

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Implication of glucocorticoid receptors in the stimulation of human glioma cell proliferation by dexamethasone

Cited by 38 publications

References 30 publications

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Cell Cycle Arrest by Glucocorticoids May Protect Normal Tissue and Solid Tumors from Cancer Therapy

Glutathione Is Involved in the Granular Storage of Dopamine in Rat PC12 Pheochromocytoma Cells: Implications for the Pathogenesis of Parkinson’s Disease

Treating gliomas with glucocorticoids: from bedside to bench

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