A novel sodium phenylacetate-dextran derivative ester inhibits the growth and angiogenesis of MCF-7ras breast cancer xenografts

We previously showed that sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran (CMDB) are both able to block the tumor growth of the breast cancer cell line MCF-7ras in athymic mice. In this study, we studied the effect of a new molecule: a CMDB esterified by phenylacetic acid (NaPaC). In vitro, NaPaC can inhibit threefold to fourfold more MCF-7ras proliferation than NaPa alone. Furthermore, we showed that the antiproliferative activity of NaPaC was dependent on phenylacetate substitution. In vivo studies showed that a very low dose of NaPaC (15 mg/kg) inhibited the MCF-7ras tumor growth of 60% without animal toxicity. The inhibition of tumor growth was concomitant with a reduction in angiogenesis and an increase in necrosis. Moreover, we demonstrated that NaPaC inhibited the paracrine mitogenic effect of MCF-7ras conditioned medium (CM) on fibroblasts and endothelial cells proliferation.