σ Binding site ligands inhibit cell proliferation in mammary and colon carcinoma cell lines and melanoma cells in culture

doi:10.1016/0014-2999(95)00115-2

European Journal of Pharmacology

Volume 278, Issue 2, 15 May 1995, Pages 151-160

https://doi.org/10.1016/0014-2999(95)00115-2 Get rights and content

Abstract

Recent evidence suggests a role for sigma (σ) binding sites in maintenance of cell growth and/or proliferation. The present study examines, for the first time, the effect of σ binding site ligands on in vitro growth of tumour cells derived from human mammary adenocarcinoma (MCF-7, MDA) and colon carcinoma (LIM 1215, WIDr), and melanoma (Chinnery). Addition of the σ ligands haloperidol, reduced haloperidol, 1,3-di(2-tolyl)guanidine (DTG), (+)- and (-)-N-allylnormetazocine (SKF 10,047), (+)- and (-)-pentazocine and rimcazole at 6.25, 12.5, 25, 50, 100 μM at the beginning of culture or 24 h later, inhibited cell proliferation in a dose-dependent manner. Light microscopy revealed cell detachment, rounding and cell death. The potency of σ ligands on melanoma cells was rimcazole > reduced haloperidol > haloperidol = (+)-pentazocine, whereas DTG and (+)- and (-)-SKF 10,047 and (-)-pentazocine had no effect even at 100 μM. In contrast, in MCF-7 cells, rimcazole > reduced haloperidol > haloperidol > (-)-pentazocine > DTG > (+)-pentazocine > (+)-SKF 10,047 > (-)-SKF 10,047. For colon cancer cells, reduced haloperidol > DTG > haloperidol = (-)-pentazocine = (+)-pentazocine = (+)-SKF 10,047. Of all the ligands tested, rimcazole and reduced haloperidol were the most potent inhibitors of cell proliferation. With the exception of one slow-growing colon cancer cell line (LIM 1215), the order of sensitivity of various cell lines to reduced haloperidol. SKF 10,047, DTG, haloperidol and (+)- and (-)-pentazocine was colon carcinoma > mammary adenocarcinoma > melanoma, whereas to rimcazole, the sensitivities of mammary adenocarcinoma and melanoma cells were comparable. The effect of σ ligands in MCF-7 and melanoma cells was not due to blockade of dopamine D₁ and D₂ receptors, serotonin (5-HT₂) receptors, N-methyl-d-aspartate (NMDA)/phencyclidine receptors, β-adrenoceptors or opioid receptors, since 100 μM SCH 23390, raclopride, mianserin, (+)-MK-801, propranolol and 1 μM naloxone respectively, were ineffective. However, mianserin and raclopride were inhibitory to melanoma cells and one colon carcinoma cell line, respectively. Taken together, the results are consistent with the recent observation that σ binding sites may play a role in cell growth and/or cell proliferation.

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Regular paperσ Binding site ligands inhibit cell proliferation in mammary and colon carcinoma cell lines and melanoma cells in culture

Abstract

Int. Rev. Exp. Pathol.

Life Sci.

Nucl. Med. Biol.

Biochem. Pharmacol.

Eur. J. Pharmacol.

Brain Res

Trends Pharmacol. Sci.

Eur. J. Pharmacol.

Life Sci.

Eur. J. Pharmacol.

Life Sci.

Eur. J. Pharmacol.

In vitro and in vivo expression of opioid and σ receptors in rat C6 glioma and mouse N18TG2 neuroblastoma cells

J. Neurochem.

Modulation of (+)-[3H]pentazocine binding to guinea-pig cerebellum by divalent cations

Mol. Pharmacol.

Overexpression of sigma receptors in non-neural human tumors

Cancer Res.

Biochemical pharmacology of sigma receptors

The selective sigma (σ) ligands DTG and (+)pentazocine dose-dependently modulate phosphorylation of synapsin I in rat cortical synaptosomes

Neuropsychopharmacology

Sigma ligands inhibit the muscarinic-induced increase in phosphatidylinositol accumulation in bovine adrenal medullary chromaffin cells

Neurochem. Res.

Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing

Cancer Res.

MHC-restricted response of CD8+ and CD4+ T cell clones from regional lymph nodes of melanoma cells

Int. J. Cancer

Regular paper
σ Binding site ligands inhibit cell proliferation in mammary and colon carcinoma cell lines and melanoma cells in culture

Modulation of (+)-[³H]pentazocine binding to guinea-pig cerebellum by divalent cations

MHC-restricted response of CD8⁺ and CD4⁺ T cell clones from regional lymph nodes of melanoma cells