Sodium phenylacetate (NaPa) induces modifications of the proliferation, the adhesion and the cell cycle of tumoral epithelial breast cells

Sodium phenylacetate (NaPa), a physiological product of phenylalanine metab olism, present in micromolar concentrations in human plasma, has been shown to induce in vivo and in vitro cytostatic antiproliferative effects at mil limolar concentrations. Cadherin molecules are powerful invasion suppressor molecules and the reduction of E-cadherin expression plays an important ro le in the invasion and metastasis of human breast cancer. In this study, we demonstrated, on one hand, that NaPa stimulated aggregation by increasing the expression of E-cadherin at the surface of breast cancer MCF-7ras cells transformed by Ha-ms oncogene and inhibited its expression in MCF-7 cells. We demonstrated that NaPa increased the formation of MCF-7ras cell aggrega ts and did not alter the formation of MCF-7 cell aggregates. By Northern bl ot, we demonstrated that the E-cadherin expression was not regulated at the transcriptional level. On the other. hand, we analyzed the cell cycle of t hese 2 cell lines after NaPa treatment and showed that NaPa induced arrest at the G1/S phase in both MCF-7 and MCF-7ras cells. bFGF increased the grow th of MCF-7 cells, but inhibited MCF-7ras cell proliferation. NaPa treatmen t suppressed the stimulation of MCF-7 cell proliferation and increased MCF- 7ras cell growth inhibition. We have demonstrated a new target of NaPa acti on in blocking the cell cycle of tumor cells in G0/G1. We suggest that the anti-proliferative effect of NaPa associated to the restoration of the cadh erin function in human mammary carcinoma cells indicates that NaPa could be a novel therapeutic agent in breast cancer.