Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21(Waf1/Cip1) and p27(Kip1)

D. A. Litvak, B. M. Evers, K. O. Hwang, M. R. Hellmich, T. C. Ko, Jr Townsend, D. W. Mercer, R. A. Hodin, R. G. Postier, David Soybel

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Abstract

Background. Intestinal mucosal turnover is a process of proliferation, differentiation, and apoptosis; the mechanisms remain largely undefined. The purpose of our study was to (I) assess the relationship between apoptosis and enterocyte differentiation and (2) determine whether the cell-cycle inhibitors, p21(Wafl/cip1) and p27(Kip1), or the apoptosis inhibitors, Bcl-2 and Bcl-X(L), may be involved. Methods. Gut-derived Caco-2 cells were treated with sodium butyrate. Apoptosis was assessed by Hoechst stain, DNA laddering, and annexin V assay; differentiation was determined by alkaline phosphatase and sucrase activity. RNA and protein were analyzed for expression of p21(Waf1/Cip1), p27(Kip1), and members of the Bcl-2 family. Results. Treatment of Caco-2 cells with sodium butyrate resulted in the concomitant induction of both differentiation (increased alkaline phosphatase and sucrase activity) and apoptosis. Increased levels of p21(Waf1/Cip1) and p27(Kip1) mRNA and protein were detected at 24 hours, occurring before apoptosis or differentiation; decreased mRNA levels of Bcl-2 and Bcl-X(L) were noted at 24 hours. Conclusions. Differentiation and apoptosis occurred simultaneously in Caco-2 cells, suggesting that apoptosis may be linked to enterocyte differentiation. The induction of p21(Waf1/cip1) and p27(KiP1) and the down- regulation of Bcl-2 and Bcl-X(L) further suggest a link between the cell- cycle mechanisms regulating enterocyte differentiation and apoptosis.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalSurgery
Volume124
Issue number2
DOIs
StatePublished - Jan 1 1998

All Science Journal Classification (ASJC) codes

  • Surgery

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    Litvak, D. A., Evers, B. M., Hwang, K. O., Hellmich, M. R., Ko, T. C., Townsend, J., Mercer, D. W., Hodin, R. A., Postier, R. G., & Soybel, D. (1998). Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21(Waf1/Cip1) and p27(Kip1). Surgery, 124(2), 161-170. https://doi.org/10.1016/S0039-6060(98)70116-3