p21WAF1 is required for butyrate-mediated growth inhibition of human colon cancer cells

摘要: A diet high in fiber is associated with a decreased incidence and growth of colon cancers. Butyrate, four-carbon short-chain fatty acid product fermentation within the colon, appears to mediate these salutary effects. We sought determine molecular mechanism by which butyrate mediates inhibition colonic cancer cells thereby elucidate link between high-fiber arrest carcinogenesis. show that concomitant arrest, induces p21 mRNA expression an immediate-early fashion, through transactivation promoter cis-element(s) located 1.4 kb transcriptional start site, independent p53 binding. Studies using specific histone hyperacetylating agent, trichostatin A, deacetylase 1 indicate induction occur involving hyperacetylation. critical importance butyrate-mediated first confirming stable overexpression gene able cause human carcinoma cell line, HT-29. Furthermore, p21-deleted HCT116 cells, we provide convincing evidence required for response hyperacetylation, but not serum starvation nor postconfluent growth. Thus, be effector butyrate-induced may important prevention