Effect of structural analogues of propionate and butyrate on colon cancer cell growth

The aim of this study was to evaluate the effects of natural short-chain fa tty acids (butyrate, propionate, valerate, acetate) and structural analogue s of butyrate and propionate on cell growth and apoptosis in three human co lonic adenocarcinoma cell lines (HT-29, Colo-320, and SW-948). We have prev iously shown that mercapto- and bromo-analogues of butyrate and propionate compete with natural short-chain fatty acids for uptake in the colonocyte. Among naturally occurring short-chain fatty acids, butyrate was the most po tent inhibitor of proliferation in all three cell lines. Propionate exhibit ed a weaker antiproliferative effect, while other short-chain fatty acids ( valerate, acetate) were ineffective. Bromo-analogues of butyrate and propio nate were more potent proapoptotic agents than butyrate. In contrast to but yrate, the analogues induced strand breaks on isolated supersoiled DNA, the effect being completely reversed by a DNA-protecting agent, spermine. We c onclude that bromo-analogues of butyrate and propionate are more potent pro apoptotic agents. than butyrate in colon cancer cells in culture. Their eff ect may be a result of diner DNA damage.