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Simultaneous but not sequential treatment with sodium butyrate improves the antiproliferative effect of alpha- or beta-interferon on a breast cancer cell line.

Clinical evidence indicates that alpha- and beta-interferon (alpha-IFN, beta-IFN) are only partially effective in human breast cancer. To improve their effectiveness, it has been proposed that differentiation inducers, such as sodium butyrate (NaB), be used to increase the IFN sensitivity of tumors. Therefore, we assessed concomitant or sequential combinations of low/intermediate concentrations of alpha-IFN or beta-IFN (10, 50 and 100 IU/ml) with a low concentration (0.1 mM) of NaB on a human breast cancer cell line (MDA-MB231), which exhibited a moderate sensitivity to IFN. Moreover, to verify the capability of NaB to potentiate IFN effectiveness by increasing IFN receptor (IFN-R) concentration, we investigated the effect of NaB on the synthesis of IFN-R. The concomitant presence of NaB and alpha-IFN or beta-IFN significantly improved the antiproliferative effect of the corresponding IFN alone. Conversely, the sequential treatment NaB-IFN did not enhance the inhibitory activity of the cytokine, although NaB was able to induce the expression of IFN-R. More likely, NaB induced the expression of some component of the IFN system, such as Stat1, Stat2 or p48, whose higher availability in the cytoplasmic compartment promotes formation of the multimeric transcription factor ISGF3, which induces the transcription of IFN-stimulated genes.