Role of activin A in induction of growth arrest and apoptosis by butyrate in colon cancer cells

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1. Colorectal tumor-suppressing effect of dietary fiber has been reportedly associated with its fermentation product butyrate. The present study investigated whether activin A mediates butyrate-induced growth arrest and apoptosis in colon cancer cells.2. Butyrate induced G1 arrest and apoptosis in human colon cancer cell line HT-29. Butyrate also stimulated activin A gene in time-and dose-dependent manner. Because trichostain A also stimulated activin A gene, the effect of butyrate is possibly associated with the inhibition of histone acetylase. Stimulation of activin A gene by butyrate seems to be specific to cancer cells, as normal cell lines showed no response to butyrate.3. Exogenous activin A did not aggect the growth of HT-29 cells. Immuneprecipitation coupled with Western blotting revealed that activin A induced phosphorylation of smad2 but not complex formation of smad2/3/4 in HT-29 cells. The cell line expressed neither smad4 mRNA nor protein. It is thus suggested that unresponsiveness to activin A in HT-29 cells is due to mutation of smad4.4. Taken together, upregulated activin A by butyrate in colon cancer cells acts as paracrine factor rather than autocrine factor. Thus activin A does not mediate butyrate-induced growth arrest and apoptosis in colon cancer cells.