The farnesyltransferase inhibitor FTI-277 suppresses the 24-kDa FGF2-induced radioresistance in HeLa cells expressing wild-type RAS.
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 microM) 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 radiosensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in G(2)/M-phase arrest in both cell types. These results clearly 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 G(2)/M-phase arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radiosensitizers of certain human tumors with wild-type RAS.
Cohen-Jonathan
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E
Laboratoire d'Oncologie Cellulaire et Moléculaire, EA/UPRES 2048, Faculté des Sciences Pharmaceutiques, Université Paul Sabatier, Centre de Lutte Contre le Cancer Claudius Regaud, 20-24 rue du Pont St-Pierre, 31052 Toulouse Cedex, France.
Toulas
C
C
Ader
I
I
Monteil
S
S
Allal
C
C
Bonnet
J
J
Hamilton
A D
AD
Sebti
S M
SM
Daly-Schveitzer
N
N
Favre
G
G
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors*; D006367:HeLa Cells; D006801:Humans; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011836:Radiation Tolerance / Q000187:drug effects*
D004791:Enzyme Inhibitors; C096856:FTI 277; D016222:Fibroblast Growth Factor 2; D008715:Methionine; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase