Butyrate and propionate downregulate ERK phosphorylation in HT-29 colon carcinoma cells prior to differentiation

We have characterized the effects of different short-chain fatty acids (SCF As) on cell growth and differentiation as well as the phosphorylation state of ERK1 and 2 in the human colon adenocarcinoma cell line HT-29. Of the fi ve SCFAs tested, only butyrate and propionate impaired cellular proliferati on. Moreover, butyrate and propionate specifically resulted in a decrease i n ERK1 and 2 phosphorylation at 3 and 6 hours post-treatment, suggesting a correlation between the ability of these SCFAs to inhibit cellular prolifer ation and decrease ERK phosphorylation. Notably, the decrease in ERK phosph orylation was observed prior to the induction of the differentiation marker s alkaline phosphatase (AP) and carcinoembryonic antigen (CEA) by butyrate and propionate from days 6 to 18 post-treatment. In the case of butyrate- a nd propionate-induced differentiation, ERK phosphorylation is a marker and may play a role in the proliferation and/or differentiation states of this cell line. (C) 2001 Lippincott Williams & Wilkins.