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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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

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 gamma 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.[1]


  1. Antiproliferative and differentiating effects of benzodiazepine receptor ligands on B16 melanoma cells. Landau, M., Weizman, A., Zoref-Shani, E., Beery, E., Wasseman, L., Landau, O., Gavish, M., Brenner, S., Nordenberg, J. Biochem. Pharmacol. (1998) [Pubmed]
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