Short-chain fatty acids induce cell cycle inhibitors in colonocytes

Gastroenterology. 1998 May;114(5):940-6. doi: 10.1016/s0016-5085(98)70313-0.


Background & aims: We tested the hypothesis that short-chain organic acids in the colon derived from dietary pectin, wheat bran, and oat bran are protective against the development of colon cancer because they induce transforming growth factor (TGF)-beta1, which in turn inhibits cell growth by inducing cyclin-directed kinase (cdk) inhibitors.

Methods: U4 human colon carcinoma cells differentiate into water- and salt-transporting columnar enterocytes and therefore model normal colonocytes. The composition and kinase activity of cdk/cyclin complexes were determined by immunoprecipitation and Western blotting studies in U4 cells treated in vitro with short-chain fatty acid (SCFA) mixtures that mimic the digestion products of wheat bran, oat bran, pectin, and cellulose (as control), which is largely unfermentable.

Results: Induction of the cdk inhibitors p21cip1 and p27kip1 by fiber-mimicking SCFA mixtures occurs much more rapidly and is many-fold greater than their induction by TGF-beta1. The SCFA mixtures most effective in causing growth inhibition and cdk inhibitor production mimicked those from wheat bran > oat bran > pectin.

Conclusions: cdk inhibitor induction by SCFA mixtures is not mediated by TGF-beta1. The SCFA mixture mimicking digested wheat bran fiber was the most effective of all mixtures tested in inhibiting cell growth through induction of cdk inhibitors.

MeSH terms

  • Cell Cycle / drug effects*
  • Cell Cycle Proteins*
  • Cell Division / drug effects
  • Colon / cytology
  • Colon / drug effects*
  • Colon / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclins / metabolism*
  • Dietary Fiber / metabolism
  • Digestion / physiology
  • Drug Combinations
  • Enzyme Inhibitors / metabolism
  • Fatty Acids / pharmacology*
  • Humans
  • Microtubule-Associated Proteins / metabolism*
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins*


  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Dietary Fiber
  • Drug Combinations
  • Enzyme Inhibitors
  • Fatty Acids
  • Microtubule-Associated Proteins
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases