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

  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},
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… 
Cyclohexylpiperazine derivative PB28, a σ2 agonist and σ1 antagonist receptor, inhibits cell growth, modulates P-glycoprotein, and synergizes with anthracyclines in breast cancer
It is suggested that the σ2 agonist PB28 could be an interesting antitumor agent either in monotherapy or in combination with conventional drugs.
Cytotoxicity of σ-Receptor Ligands Is Associated with Major Changes of Cellular Metabolism and Complete Occupancy of the σ-2 Subpopulation
Because cytotoxicity occurred at concentrations 2 orders of magnitude higher than IC50 values for inhibition of cellular 11C-SA4503 binding, high (99%) occupancy of σ-2 receptors is associated with loss of cell viability.
Synthesis, pharmacological evaluation, and σ1 receptor interaction analysis of hydroxyethyl substituted piperazines.
The potent σ1 receptor ligand 7c was able to inhibit selectively the growth of three human tumor cell lines with IC50 values in the low micromolar range.
Structure–Activity Relationships within a Series of σ1 and σ2 Receptor Ligands: Identification of a σ2 Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma
Preliminary investigations indicated that the mechanism of metastatic malignant melanoma cell death induced by BS148 is due, at least in part, to apoptosis.
2‐Aminopyridine Derivatives as Potential σ2 Receptor Antagonists
The data support the new 2‐aminopyridines as high‐affinity σ ligands with σ2 antagonist and σ1 agonist activity, and, despite the lack of significant ρ2 versus ρ1 selectivity, these novel compounds may be better tools for σ receptor research than the known low-affinityρ2 antagonists.
σ1 and σ2 receptor binding affinity and selectivity of SA4503 and fluoroethyl SA4503
This protocol, displacement of [3H]DTG binding to ρ2 sites using (+)‐pentazocine (200 nM) to mask σ1 sites, was validated by the proper rank order of σ2 inhibitory potencies shown by a panel of additional ligands.
Distribution of sigma receptors in EMT‐6 cells: preliminary biological evaluation of PB167 and potential for in‐vivo PET
The results showed that both σ1 and ρ2 receptors were overexpressed in EMT‐6 cells and that the ligand PB167 can be positively considered for radiosynthesis preparation in order to suitably visualize σ2 receptors by the in‐vivo PET technique and correlate their presence to tumour proliferation.
σ2 Receptors: Regulation of Cell Growth and Implications for Cancer Diagnosis and Therapeutics
Current evidence suggests that σ2 receptors may be useful targets for development of antineoplastic agents that will be effective against drug-resistant tumors and targeted by noninvasive imaging agents thatwill be able to detect many types of tumors, monitor their growth, and perhaps detect and treat tumors at metastatic sites.
New adamantane phenylalkylamines with σ-receptor binding affinity and anticancer activity, associated with putative antagonism of neuropathic pain.
Encouraging results were observed with 4a in vivo on mice, suggesting putative antimetastatic and analgesic activities of this compound.


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
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.
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.
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.
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.
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.
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.