The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2- induced radioresistance in HeLa cells expressing wild-type RAS

Elizabeth Cohen-Jonathan; Christine Toulas; Isabelle Ader; Sylvia Monteil; Cuider Allal; Jacques Bonnet; Andrew D. Hamilton; Said M. Sebti; Nicolas Daly-Schveitzer; Gilles Favre

doi:10.2307/3580225

The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2- induced radioresistance in HeLa cells expressing wild-type RAS

Elizabeth Cohen-Jonathan, Christine Toulas, Isabelle Ader, Sylvia Monteil, Cuider Allal, Jacques Bonnet, Andrew D. Hamilton, Said M. Sebti, Nicolas Daly-Schveitzer, Gilles Favre

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

In this paper, we describe the effect of the inhibitor of farnesyltransferase (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in human cells expressing wild-type RAS. Treatment with FTI- 277 (20 μM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radio- sensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G₂/M-phase arrest in both cell types. These results dearly demonstrate that at least one farnesylated protein is involved in the regulation of the radioresistance induced by the 24-kDa isoform of FGF2. Furthermore, the radiation-induced G₂/M-phase arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radio-sensitizers of certain human tumors with wild-type RAS.

Original language	English (US)
Pages (from-to)	404-411
Number of pages	8
Journal	Radiation Research
Volume	152
Issue number	4
DOIs	https://doi.org/10.2307/3580225
State	Published - Oct 1999

ASJC Scopus subject areas

Biophysics
Radiation
Radiology Nuclear Medicine and imaging

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title = "The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2- induced radioresistance in HeLa cells expressing wild-type RAS",

abstract = "In this paper, we describe the effect of the inhibitor of farnesyltransferase (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in human cells expressing wild-type RAS. Treatment with FTI- 277 (20 μM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radio- sensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G2/M-phase arrest in both cell types. These results dearly demonstrate that at least one farnesylated protein is involved in the regulation of the radioresistance induced by the 24-kDa isoform of FGF2. Furthermore, the radiation-induced G2/M-phase arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radio-sensitizers of certain human tumors with wild-type RAS.",

author = "Elizabeth Cohen-Jonathan and Christine Toulas and Isabelle Ader and Sylvia Monteil and Cuider Allal and Jacques Bonnet and Hamilton, {Andrew D.} and Sebti, {Said M.} and Nicolas Daly-Schveitzer and Gilles Favre",

year = "1999",

month = oct,

doi = "10.2307/3580225",

language = "English (US)",

volume = "152",

pages = "404--411",

journal = "Radiation Research",

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AU - Cohen-Jonathan, Elizabeth

AU - Toulas, Christine

AU - Ader, Isabelle

AU - Monteil, Sylvia

AU - Allal, Cuider

AU - Bonnet, Jacques

AU - Hamilton, Andrew D.

AU - Sebti, Said M.

AU - Daly-Schveitzer, Nicolas

AU - Favre, Gilles

PY - 1999/10

Y1 - 1999/10

N2 - In this paper, we describe the effect of the inhibitor of farnesyltransferase (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in human cells expressing wild-type RAS. Treatment with FTI- 277 (20 μM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radio- sensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G2/M-phase arrest in both cell types. These results dearly demonstrate that at least one farnesylated protein is involved in the regulation of the radioresistance induced by the 24-kDa isoform of FGF2. Furthermore, the radiation-induced G2/M-phase arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radio-sensitizers of certain human tumors with wild-type RAS.

AB - In this paper, we describe the effect of the inhibitor of farnesyltransferase (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in human cells expressing wild-type RAS. Treatment with FTI- 277 (20 μM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radio- sensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G2/M-phase arrest in both cell types. These results dearly demonstrate that at least one farnesylated protein is involved in the regulation of the radioresistance induced by the 24-kDa isoform of FGF2. Furthermore, the radiation-induced G2/M-phase arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radio-sensitizers of certain human tumors with wild-type RAS.

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The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2- induced radioresistance in HeLa cells expressing wild-type RAS

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