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, D. I. 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

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Caco-2 Cells
Butyrates
Apoptosis
Enterocytes
Sucrase
Butyric Acid
Alkaline Phosphatase
Cell Cycle
Cyclin-Dependent Kinase Inhibitor p27
Messenger RNA
Annexin A5
Coloring Agents
Down-Regulation
RNA
DNA

ASJC Scopus subject areas

  • Surgery

Cite this

Litvak, D. A., Evers, B. M., Hwang, K. O., Hellmich, M. R., Ko, T. C., Townsend, J., ... Soybel, D. I. (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

Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21(Waf1/Cip1) and p27(Kip1). / Litvak, D. A.; Evers, B. M.; Hwang, K. O.; Hellmich, M. R.; Ko, T. C.; Townsend, Jr; Mercer, D. W.; Hodin, R. A.; Postier, R. G.; Soybel, D. I.

In: Surgery, Vol. 124, No. 2, 01.01.1998, p. 161-170.

Research output: Contribution to journalArticle

Litvak, DA, Evers, BM, Hwang, KO, Hellmich, MR, Ko, TC, Townsend, J, Mercer, DW, Hodin, RA, Postier, RG & Soybel, DI 1998, 'Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21(Waf1/Cip1) and p27(Kip1)', Surgery, vol. 124, no. 2, pp. 161-170. https://doi.org/10.1016/S0039-6060(98)70116-3
Litvak, D. A. ; Evers, B. M. ; Hwang, K. O. ; Hellmich, M. R. ; Ko, T. C. ; Townsend, Jr ; Mercer, D. W. ; Hodin, R. A. ; Postier, R. G. ; Soybel, D. I. / Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21(Waf1/Cip1) and p27(Kip1). In: Surgery. 1998 ; Vol. 124, No. 2. pp. 161-170.
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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.",
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T1 - Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21(Waf1/Cip1) and p27(Kip1)

AU - Litvak, D. A.

AU - Evers, B. M.

AU - Hwang, K. O.

AU - Hellmich, M. R.

AU - Ko, T. C.

AU - Townsend, Jr

AU - Mercer, D. W.

AU - Hodin, R. A.

AU - Postier, R. G.

AU - Soybel, D. I.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - 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.

AB - 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.

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