Butyrate-induced G2/M block in Caco-2 colon cancer cells is associated with decreased p34cdc2 activity

Butyrate, a short-chain fatty acid, has been reported to inhibit proliferation and stimulate differentiation in multiple cancer cell lines. Whereas the effects of butyrate on cellular differentiation are well documented, the relationship between butyrate-induced differentiation and its effect on cell cycle traverse is less well understood. The purpose of this study was to investigate the effects of butyrate on the regulatory proteins of the G(2)/M traverse in the Caco-2 colon cancer cell model. We demonstrated that the inhibition of proliferation and increased cellular differentiation after treatment of Caco-2 cells with butyrate were associated with a significant G(2)/M cell cycle block. Although protein levels of the major G(2)/M regulatory protein, p34(cdc2) were unchanged, a decrease in p34(cdc2) activity was noted. Despite this decrease in activity, the inhibitory tyrosine phosphorylation of p34(cdc2) was decreased, suggesting that other factors are responsible for the decreased kinase activity. The reduced activity of p34(cdc2) provides a possible mechanism for the accumulation of Caco-2 cells in the G(2)/M cell cycle compartment following exposure to butyrate, This cell system provides a new model for studies of G(2)/M cell cycle perturbations.