Antiproliferative and cytotoxic effects of some σ2 agonists and σ1 antagonists in tumour cell lines

@article{Colabufo2004AntiproliferativeAC,
  title={Antiproliferative and cytotoxic effects of some $\sigma$2 agonists and $\sigma$1 antagonists in tumour cell lines},
  author={Nicola Antonio Colabufo and Francesco Berardi and Marialessandra Contino and Mauro Niso and Carmen Abate and Roberto Perrone and Vincenzo Tortorella},
  journal={Naunyn-Schmiedeberg's Archives of Pharmacology},
  year={2004},
  volume={370},
  pages={106-113}
}
To establish the activity of σ ligands at σ1 and σ2 receptor, we chose two tumour cell lines, the human SK-N-SH neuroblastoma and the rat C6 glioma lines, which express σ2 receptors at a high density and σ1 receptors in their high-affinity or low-affinity state. We tested the σ2 receptor agonist PB28 and the σ2 antagonist AC927, and (+)-pentazocine and NE100 as agonist and antagonist, respectively, at σ1 receptors, with regard to antiproliferative and cytotoxic effects. In addition, 1,3-di(2… 
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References

SHOWING 1-10 OF 37 REFERENCES
σ2 Receptors regulate changes in sphingolipid levels in breast tumor cells
Cytotoxic effects of sigma ligands: sigma receptor-mediated alterations in cellular morphology and viability
TLDR
The morphological effects of several neuroleptics as well as other novel and prototypic sigma ligands were examined by addition to cultures of C6 glioma cells, showing a remarkable specificity for compounds exhibiting sigma receptor binding affinity.
Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent tumor cell lines.
TLDR
The high density of sigma-1 and sigma 2-binding sites in these cell lines suggests important cellular functions in cancer, as well as potential diagnostic utility for tumor-imaging agents which target sigma sites.
Characterization of two novel sigma receptor ligands: antidystonic effects in rats suggest sigma receptor antagonism.
TLDR
BD1047 and BD1063 appear to act as antagonists at sigma sites and may represent promising new tools for probing other functional effects associated with sigma binding sites.
Sigma-2 receptor agonists activate a novel apoptotic pathway and potentiate antineoplastic drugs in breast tumor cell lines.
TLDR
The ability of sigma-2 receptor agonists to induce cell death by a mechanism consistent with apoptosis is demonstrated, suggesting the involvement of a novel p53- and caspase-independent apoptotic pathway used by s Sigma-2 receptors, which is distinct from mechanisms used by some DNA-damaging, antineoplastic agents and other apoptotic stimuli.
New sigma and 5-HT1A receptor ligands: omega-(tetralin-1-yl)-n-alkylamine derivatives.
Two series of compounds that are structurally related to benzomorphans, derived by structural modification of arylpiperazines with high 5-HT1A affinity and moderate sigma affinity, were prepared in
Modulation of cellular calcium by sigma-2 receptors: release from intracellular stores in human SK-N-SH neuroblastoma cells.
TLDR
Prolonged exposure of cells to sigma-receptor ligands resulted in a latent and sustained rise in [Ca(2+)](i), with a pharmacological profile identical to that of the transient rise.
Novel ceramide analogues display selective cytotoxicity in drug-resistant breast tumor cell lines compared to normal breast epithelial cells.
TLDR
Evaluating the cytotoxic potency of several novel ceramide analogues in the drug-resistant breast tumor cell lines and compared their cytotoxicity in normal breast epithelial cells could identify novel targets that may lead to development of anti-neoplastic agents with a higher therapeutic index.
...
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