Sodium butyrate modulates cell cycle-related proteins in HT29 human colonic adenocarcinoma cells

Sodium butyrate (NaB), a product of colonic fermentation of dietary fibre, has been shown to inhibit cell proliferation by blocking cells in the G(0)/G(1) phase of the cell cycle through a mechanism of action still not completely understood. We investigated the effect of NaB on the level of some G(1) phase-related proteins in a colon carcinoma cell line (HT29). In particular, we addressed our attention to cyclin D1 (the key regulator of GIS progression), p21(waf1/cip1) (the main inactivator of the cyclin D/cdk complex), and p53 (the most important regulator of p21(waf1/cip1) gene transcription). At inhibitory concentrations (higher than 1 mM) NaB reduced cyclin D1 and p53 level in a dose-dependent manner and sustained the synthesis of p21(waf1/cip1), probably in a p53-independent way, accounting for the cole, block observed by how cytometry. Present results provide further evidence on the molecular mechanism at the basis of the physiological role of NaB and support the hypothesis that an unbalanced diet, poor in carbohydrates and therefore in NaB, could result in functional alterations with clinical and carcinogenic implications.