RT Journal Article SR Electronic T1 A Prenylation Inhibitor (Sodium Phenylacetate) Differently Affects MCF-7 Cell Death when ras is Overexpressed, Partly Involving P42/44, JNK and P38 Kinase Activations JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1029 OP 1037 VO 28 IS 2A A1 MÉLANIE DI BENEDETTO A1 MICHEL CRÉPIN A1 MICHEL KRAEMER A1 OLIVIER OUDAR YR 2008 UL http://ar.iiarjournals.org/content/28/2A/1029.abstract AB Background: Sodium phenylacetate (NaPa) inhibits breast cancer cell proliferation decreasing prenylation of small G proteins including Ras. Materials and Methods: Aponecrosis induced by NaPa in MCF-7 and MCF-7ras breast cancer cells was evaluated by measuring Annexin V/PI labelling by flow cytometry. Specific inhibitors of p42/44 (PD 98059), p38 (SB 600125) and JNK (SP 202190) in association with NaPa were also tested. Mitogen-activated kinase (MAPK) activation was measured by immunoprecipitation. Results: NaPa induced cell death more efficiently (80%) in the MCF-7ras cells compared to the MCF-7 cells (60%). NaPa activated ERK 1/2 and its combination with PD 98059 decreased cell death in the MCF-7ras cells in contrast to the MCF-7 cells. Combination of NaPa with specific inhibitors of both JNK and p38 kinases also partly decreased MCF-7ras cell death. Conclusion: NaPa induced cell death differently when ras was overexpressed in breast cancer cells, partly involving p42/44, JNK and p38 pathways.