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  • Title: Inhibition of B16 melanoma cell proliferation and alterations in p21 ras expression induced by interceptors of signal transduction pathways.
    Author: Nordenberg J, Goldwasser I, Zoref-Shani E, Beery E, Sidi Y.
    Journal: Isr J Med Sci; 1996 Dec; 32(12):1153-7. PubMed ID: 9007143.
    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.
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