Inhibition of B16 melanoma cell proliferation and alterations in P21 ras expression induced by interceptors of signal transduction pathways

J. Nordenberg, I. Goldwasser, E. Zoref-Shanf, F. Beery, Y. Sidi

Research output: Contribution to journalArticlepeer-review

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 p21 ras. 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.

Original languageEnglish
Pages (from-to)1153-1157
Number of pages5
JournalIsrael Journal of Medical Sciences
Volume32
Issue number12
StatePublished - Dec 1996
Externally publishedYes

Keywords

  • B16 melanoma
  • Growth inhibition
  • Signal transduction
  • p21 ras expression

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