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 G0/G1 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 G1 phase-related proteins in a colon carcinoma cell line (HT29). In particular, we addressed our attention to cyclin D1 (the key regulator of G1S progression), p21waf1/cip1 (the main inactivator of the cyclin D/cdk complex), and p53 (the most important regulator of p21waf1/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 p21waf1/cip1, probably in a p53-independent way, accounting for the G0/G1 block observed by flow 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.
Coradini
D
D
Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy. coradini@istitutotumori.mi.it
Pellizzaro
C
C
Marimpietri
D
D
Abolafio
G
G
Daidone
M G
MG
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D020148:Butyric Acid / Q000494:pharmacology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000187:drug effects* / Q000378:metabolism; D002455:Cell Division; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019073:HT29 Cells; D006801:Humans
D018797:Cell Cycle Proteins; D020148:Butyric Acid