A Prenylation Inhibitor (Sodium Phenylacetate) Differently Affects MCF-7 Cell Death when ras is Overexpressed, Partly Involving P42/44, JNK and P38 Kinase Activations

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.