SODIUM PHENYLACETATE MODULATES THE SYNTHESIS OF AUTOCRINE AND PARACRINE GROWTH-FACTORS SECRETED BY BREAST-CANCER CELL-LINES

Sodium Phenylacetate (NaPa) has been shown to suppress tumor growth an d promote differentiation in experimental models Thus, we have previou sly shown an inhibition of MCF-7ras cell proliferation by NaPa both in vitro and in vivo on xenographted tumors. In order to study the actio n of NaPa on the synthesis of paracrine or autocrine growth factors, c onditioned media were prepared from breast pretumoral HBL100 cells, tu moral MCF-7 and MCF-7ras cells in the presence of NaPa. Growth factor activities of these media were tested on Balb c/3T3 fibroblasts and on the above breast tumor cells. Conditioned media from the 3 cell types contained different mitogenic activities when tested on the same cell lines NaPa treatment for 24 hours inhibited differentially and dose-d ependently the mitogenic activity of conditioned media. Inhibitions of HBL100 and MCF-7 cell proliferation by MCF-7ras medium conditioned wi th 20mM NaPa reached 75% and 48% respectively In contrast, NaPa treate d MCF-7 conditioned medium decreased HBL100 and MCF-7ras proliferation by 49% and 72%, respectively, at the same NaPa concentration. The eff iciency of NaPa inhibition reached an optimum as soon as one day after treatment Among growth factors secreted by MCF-7and MCF-7ras, TGF bet a synthesis is inhibited and stimulated in MCF-7 and MCF-7ras cells re spectively after NaPa treatment. We showed that NaPa modifies the synt hesis of growth factors secreted by MCF-7 and MCF-7ras tumor cells lea ding to cell proliferation inhibitions. The synthesis of these previou sly identified factors was more involved in MCF-7 cells than fibroblas t cell proliferation. In vitro and in vivo NaPa inhibition of MCF-7ras cells which secreted higher levels of these growth factors could be e xplained by this mechanism of action.