Digested Fiber from Wheat Bran Induces cdk Inhibitors which Block Colon Epithelial Cells in G1
We have tested the hypothesis that short chain organic acids in the colon derived from dietary pectin, wheat bran, oat bran, and cellulose are protective against the development of colon cancer because they cause growth arrest by inducing cyclin-directed kinase (cdk) inhibitors. A more quiescent colonic epithelium is less susceptible to mutagens which can lead to mutations or deletions in the major genes implicated in the progression to colon cancer: ras, p53, and APC1 or in the genes involved in TGFβ response such as TβRII2 or the Smad genes which are intermediates in TGFβ signaling.3,4 TGFβ1 is a small protein found in vivo which is the most potent epithelial cell growth inhibitor known. High levels of TGFβ1 mRNA and peptide are found at the top of the colonic crypt in the region of terminally differentiated cells.5,6 Injected TGFβl shortens colonic crypts.7 These observations suggest that TGFβ1 induces differentiation and growth arrest in vivo. TGFβ1 inhibits colonocyte proliferation by inhibiting phosphorylation of the retinoblastoma protein through blocking the activity of cdk/cyclin complexes. TGFβ1 inhibits cdk kinases by inducing the cdk inhibitors p15 and p21 and causing accumulation of p27.8–10 Thus short chain organic acids in the colon derived from dietary fiber could act directly to induce cdk inhibitors, or they could work indirectly by first inducing TGFβl, which in turn induced cdk inhibitors.
KeywordsWheat Bran Sodium Butyrate Colonic Crypt Induce Growth Arrest Sodium Propionate
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