Inhibition of B16 melanoma cell proliferation and alterations in p21 ras expression induced by interceptors of signal transduction pathways.

Abstract

Anti-tumor effects of agents known to intervene with signal transduction pathways (ras and protein kinase c cascades) were examined in the B16 melanoma cell model. The compounds examined included: lovastatin, an inhibitor of HMG-CoA reductase, which interferes with membrane localization of p21 ras protein; H-7, a classic inhibitor of protein kinase C; and tiazofurin, a GTP depleting agent, that might affect the GTP/GDP ratio on p21ras. The three agents were found to inhibit the proliferation of B16 melanoma cells. Only tiazofurin, as expected, induced a significant decrease in GTP levels. Lovastatin and H-7 altered p21 subcellular localization. They reduced membrane expression of p21 ras, while increasing its expression in the cytosol. Following tiazofurin treatment a trend towards increased membranal p21 was observed. These results suggest that p21 is a target for the action of signal transduction inhibitors. However, the relationship between growth inhibition and altered p21 expression is not yet clear.

Cite this paper

@article{Nordenberg1996InhibitionOB, title={Inhibition of B16 melanoma cell proliferation and alterations in p21 ras expression induced by interceptors of signal transduction pathways.}, author={Jardena Nordenberg and I. E. Goldwasser and Esther Zoref-Shani and Einat Beery and Yechezkel Sidi}, journal={Israel journal of medical sciences}, year={1996}, volume={32 12}, pages={1153-7} }