Growth inhibition of human melanoma tumor cells by the combination of sodium phenylacetate (NaPA) and substituted dextrans and one NaPA-dextran conjugate.

We have studied the cytostatic effects of sodium phenylacetate (NaPA) in association with several substituted dextrans on human tumor melanoma 1205LU cells. We show that NaPA alone inhibits the growth of these cells (IC50 = 3.9 mM) while a weak inhibitory effect appears at a concentration of 37 microM (10 microg/ml) for a dextran methyl carboxylate benzylamide (LS17-DMCB). The precursors of LS17-DMCB [T40 Dextran and carboxymethyl dextran (LS17-DMC)] did not affect the growth of 1205LU cells. To potentiate the inhibitory activity of NaPA at low concentrations (below 5.6 mM), we have tested NaPA and LS17-DMCB in physical mixture (association) or linked together covalently (this conjugate is termed 'LS17-NaPaC'). We have observed an increase of the 1205LU cell growth inhibition effect with NaPA in association (IC50 1.8 mM). For a concentration of 5 mM of NaPA (free in the case of association or linked in the case of conjugate), the association with dextran derivative exhibits a 4.6-fold higher efficacy than with NaPA alone (9 versus 41% surviving fraction), while the conjugate is 1.3-fold smaller (52% growth inhibition). By performing isobologram analysis of the IC50 data, we have shown a synergistic effect for a particular molar ratio of NaPA and LS17-DMCB (NaPA:LS17-DMCB = 0.35).