Cytostatic and pro-apoptotic effects of a novel phenylacetate-dextran derivative (NaPaC) on breast cancer cells in interactions with endothelial cells.

We have tested a novel hybrid molecule made of carboxymethylbenzylamide dextran (CMDB) and sodium phenylacetate (NaPa) groups, called the CMDB-NaPa ester (NaPaC), on the proliferation of breast cancer and endothelial cells as well as paracrine effects between these two cell types. Our results showed that NaPaC inhibited the proliferation of MDA-MB-231 cells and MCF-7 cells in a dose-dependent manner. NaPaC was 20-fold more active on highly invasive MDA-MB-231 cells than the NaPa parental molecule. On MCF-7 cells, which present a less aggressive phenotype, NaPaC was only 3-fold more active than the NaPa parental molecule. Furthermore, NaPaC had only a slight effect on the proliferation of primary cultured endothelial cells (HUVEC). A cytostatic effect of NaPaC on tumor cells was observed with cells accumulating in G0/G1 phase after 96 h of treatment. In addition, NaPaC induced a strong apoptotic effect on the two breast cancer cell lines. Conditioned media (CM) from tumor cells inhibited HUVEC proliferation, and this effect was enhanced in the presence of NaPaC (6 mM) and NaPa (10 mM). In addition to this cytostatic effect, CM from tumor cells induced a HUVEC early apoptosis which was increased, mainly, in the presence of NaPa (15 mM). Thus, this study shows that NaPaC is a more powerful anti-proliferative molecule than its parental NaPa molecule, with cytostatic and pro-apoptotic effects on MDA-MB-231 and MCF-7 tumor cells. Also, both molecules increased a pro-apoptotic effect of tumor cells on HUVEC.