Antiproliferative and differentiating effects of benzodiazepine receptor ligands on B16 melanoma cells

Marina Landau, Abraham Weizman, Esther Zoref-Shani, Einat Beery, Lina Wasseman, Ofer Landau, Moshe Gavish, Sarah Brenner, Jardena Nordenberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

In this study, we evaluated the effect of several ligands active at the central-type and peripheral-type benzodiazepine receptor (BzR) (clonazepam, diazepam, PK11195 and Ro5-4864) on the growth and differentiation of B16 melanoma cells. All tested BzR ligands were able to suppress proliferation of the cells at the micromolar range and in a concentration-dependent manner. However, agents selectively active at the peripheral-type BzR (PK11195 and Ro5-4864) exhibited more potent antiproliferative activity. In addition, the BzR ligands were demonstrated to affect the cell cycle by reducing the percent of cells in the S phase and increasing the percent in the G2/M phase. BzR ligands induced cellular phenotypic alterations, which have been previously shown to be associated with melanoma cell differentiation. These alterations included: marked morphological changes, enhancement of melanogenesis, lipid accumulation and increase in the activity of γ glutamyl transpeptidase. All BzR ligands induced a marked reduction in the concentration of UTP and most of them did the same in GTP and CTP, while ATP levels were not significantly altered. In summary, BzR ligands (clonazepam, diazepam, PK11195 and Ro5-4864) were found to exert antitumor effects in B16 melanoma cells. These findings encourage further studies of a possible therapeutic potential of BzR ligands in treatment of melanoma. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1029-1034
Number of pages6
JournalBiochemical Pharmacology
Volume56
Issue number8
DOIs
StatePublished - 15 Oct 1998

Keywords

  • Benzodiazepine receptor
  • Cell cycle
  • Cell proliferation
  • Melanoma
  • γ glutamyl transpeptidase

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