GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2- M enrichment in A549 cells

Karine Miquel, Anne Pradines, Jiazhi Sun, Yimin Qian, Andrew D. Hamilton, Saïd M. Sebti, Gilles Favre

Research output: Contribution to journalArticlepeer-review

Abstract

The mechanism by which the geranylgeranyltransferase I inhibitor GGTI- 298 and the farnesyltransferase inhibitor FTI-277 inhibit human tumor growth is not known. Herein, we demonstrate that in the human lung adenocarcinoma A849 cells, GGTI-298 induced a G1-G0 block whereas FTI-277 induced an enrichment in the G2-M phase of the cell cycle. Although FTI-277, GGTI-298, and compactin inhibited A549 cell growth, only GGTI-298 and compactin induced apoptosis as demonstrated by four criteria: 4',6-diamidine-2- phenylindoledihydrochloride staining, terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling, DNA fragmentation assay, and flow cytometry. Furthermore, the involvement of geranylgeranylated proteins in apoptotic pathways was confirmed by demonstrating that geranylgeraniol was able to block the ability of compactin tn induce apoptosis. These results suggest that protein geranylgeranylation is critical for the control of programmed cell death and that, in A549 cells, farnesylated and geranylgeranylated proteins are involved in G2-M and G0-G1, respectively.

Original languageEnglish (US)
Pages (from-to)1846-1850
Number of pages5
JournalCancer Research
Volume57
Issue number10
StatePublished - May 15 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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