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Genes modulated by histone acetylation as new effectors of butyrate activity
F Della Ragione1, V Criniti, V Della Pietra
1Department of Biochemistry and Biophysics F. Cedrangolo, Medical School, Second University of Naples, Italy. dellarag@cds.unina.it
Abstract:
A wealth of evidence correlates the chemopreventive activity of a fiber-rich diet with the production of butyrate. In order to identify the genes transcriptionally modulated by the molecule, we analyzed the expression profile of butyrate-treated colon cancer cells by means of cDNA expression arrays. Moreover, the effect of trichostatin A, a specific histone deacetylase inhibitor, was studied. A superimposable group of 23 genes out of 588 investigated is modulated by both butyrate and trichostatin A. Among them, a major target was tob-1, a gene involved in the control of cell cycle. tob-1 is also up-regulated by butyrate in a neuroblastoma-derived cell line, and its overexpression in the colon cells caused growth arrest. Our findings represent an extensive analysis of genes modulated by butyrate and identify completely new effectors of its biological activities.
Insights
Dietary fiber promotes chemoprevention via butyrate production. This study identified 23 genes, including tob-1, modulated by butyrate and trichostatin A in colon cancer cells, revealing new biological effectors.
Area of Science:
- Molecular biology
- Cancer research
- Genomics
Background:
- Fiber-rich diets are linked to cancer chemoprevention through butyrate production.
- Butyrate's specific gene targets and mechanisms remain incompletely understood.
Purpose of the Study:
- To identify genes transcriptionally modulated by butyrate in colon cancer cells.
- To investigate the role of histone deacetylase inhibition in butyrate's effects.
- To uncover novel molecular targets of butyrate's biological activities.
Main Methods:
- Gene expression profiling using cDNA expression arrays on butyrate-treated colon cancer cells.
- Comparative analysis with cells treated with trichostatin A, a histone deacetylase inhibitor.
- Validation of target gene tob-1 expression and functional analysis in cell lines.
Main Results:
- A common set of 23 genes out of 588 analyzed were modulated by both butyrate and trichostatin A.
- The gene tob-1, involved in cell cycle control, was identified as a major target.
- Tob-1 upregulation by butyrate was observed in colon and neuroblastoma cells, leading to growth arrest.
Conclusions:
- This study provides an extensive analysis of butyrate-modulated genes in colon cancer.
- Tob-1 is identified as a key effector of butyrate's antiproliferative effects.
- Novel molecular pathways influenced by butyrate in cancer prevention are revealed.