The antiproliferative effect of dietary fiber phenolic compounds ferulic acid and p-coumaric acid on the cell cycle of Caco-2 cells

Nutr Cancer. 2011;63(4):611-22. doi: 10.1080/01635581.2011.538486.

Abstract

Epidemiological and animal studies have shown that dietary fiber is protective against the development of colon cancer. Dietary fiber is a rich source of the hydroxycinnamic acids ferulic acid (FA) and p-coumaric acid (p-CA), which both may contribute to the protective effect. We have investigated the effects of FA and p-CA treatment on global gene expression in Caco-2 colon cancer cells. The Caco-2 cells were treated with 150 μM FA or p-CA for 24 h, and gene expression was analyzed with cDNA microarray technique. A total of 517 genes were significantly affected by FA and 901 by p-CA. As we previously have found that FA or p-CA treatment delayed cell cycle progression, we focused on genes involved in proliferation and cell cycle regulation. The expressions of a number of genes involved in centrosome assembly, such as RABGAP1 and CEP2, were upregulated by FA treatment as well as the gene for the S phase checkpoint protein SMC1L1. p-CA treatment upregulated CDKN1A expression and downregulated CCNA2, CCNB1, MYC, and ODC1. Some proteins corresponding to the affected genes were also studied. Taken together, the changes found can partly explain the effects of FA or p-CA treatment on cell cycle progression, specifically in the S phase by FA and G(2)/M phase by p-CA treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Caco-2 Cells
  • Cell Cycle / drug effects*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Division / drug effects
  • Cell Proliferation / drug effects*
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Coumaric Acids / pharmacology*
  • Cyclin A2 / genetics
  • Cyclin A2 / metabolism
  • Cyclin B1 / analysis
  • Cyclin B1 / genetics
  • Cyclin B1 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Down-Regulation
  • GTPase-Activating Proteins / genetics
  • GTPase-Activating Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Mitosis / drug effects
  • Oligonucleotide Array Sequence Analysis
  • Propionates
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • S Phase / drug effects
  • Up-Regulation / drug effects

Substances

  • Autoantigens
  • CCNA2 protein, human
  • CCNB1 protein, human
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • CEP250 protein, human
  • Chromosomal Proteins, Non-Histone
  • Coumaric Acids
  • Cyclin A2
  • Cyclin B1
  • Cyclin-Dependent Kinase Inhibitor p21
  • GTPase-Activating Proteins
  • MYC protein, human
  • Microtubule-Associated Proteins
  • Propionates
  • Proto-Oncogene Proteins c-myc
  • RABGAP1 protein, human
  • structural maintenance of chromosome protein 1
  • ferulic acid
  • p-coumaric acid