Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice.

Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB[SUBLS4]) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB[SUBLS4] may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose- and time-dependent manner. The addition of CMDB[SUBLS4] potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB[SUBLS4] and NaPa concentrations. In nude mice, CMDB[SUBLS4] (150 mg kg[SUP-1]) or NaPa (40 mg kg[SUP-1]) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB[SUBLS4] and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB[SUBLS4] action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB[SUBLS4] added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB[SUBLS4] involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth. [ABSTRACT FROM AUTHOR]