The farnesyltransferase inhibitor FTI-277 radiosensitizes H-ras-transformed rat embryo fibroblasts

Eric J. Bernhard, Gary Kao, Adrienne D. Cox, Said M. Sebti, Andrew D. Hamilton, Ruth J. Muschel, W. Gillies McKenna

Research output: Contribution to journalArticlepeer-review

Abstract

Many tumor cells have a greater resistance to ionizing radiation than their normal counterparts, suggesting that the development of drugs that can reduce that radioresistance would potentiate the efficacy of radiation therapy. Because activated H-ras expression has been shown to markedly increase radiation resistance in some transformed cells, the inactivation of H-ras would then be predicted to radiosensitize these tumor cells, while leaving normal cells unaffected. H-ras depends for activity upon farnesylation, which can be blocked by farnesylation inhibitors, including the compound FTI-277. In keeping with this prediction, inhibition of H-ras processing using FTI-277 resulted in higher levels of apoptosis after irradiation and increased radiosensitivity in H-ras-transformed rat embryo cells but did not affect control cells. These experiments suggest that farnesylation inhibitors may prove clinically useful as radiosensitizers of tumors that depend on ras function.

Original languageEnglish (US)
Pages (from-to)1727-1730
Number of pages4
JournalCancer Research
Volume56
Issue number8
StatePublished - Apr 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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