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, David 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, David 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, David 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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title = "Butyrate-induced differentiation of Caco-2 cells is associated with apoptosis and early induction of p21(Waf1/Cip1) and p27(Kip1)",
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, David 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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DO - 10.1016/S0039-6060(98)70116-3

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JF - Surgery (United States)

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