Role of caspase activation in butyrate-induced terminal differentiation of HT29 colon carcinoma cells

Jiyang Cai, Yan Chen, T. J. Murphy, Dean P. Jones, Alan C. Sartorelli

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Colon epithelial cells have a defined life span and undergo terminal differentiation as they mature and migrate to the luminal surface. The differentiation process can be induced in cultured colon cancer cells by sodium butyrate, which induces expression of various differentiation markers followed subsequently by cell death. In the present study, HT29 colorectal carcinoma cells were shown to undergo butyrate-induced caspase activation that was mainly produced through a mitochondrial pathway. Inhibition of caspase activation, either by peptide pan caspase inhibitor Z-VAD-FMK, by caspase 9 inhibitor Z-LEHD-FMK, or by overexpression of Bcl-XL, also inhibited the expression of differentiation markers. These findings suggest (a) that terminal differentiation of HT29 colon carcinoma cells is tightly linked to caspase activation and (b) that increased expression of anti-apoptotic members of the Bcl-2 family of proteins, as well as other inhibitors of caspase activation, has the potential to inhibit terminal differentiation and thereby may contribute to the progression of colon cancer.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume424
Issue number2
DOIs
StatePublished - Apr 15 2004
Externally publishedYes

Fingerprint

Caspase Inhibitors
Butyrates
Caspases
Colon
Chemical activation
Differentiation Antigens
Cells
Carcinoma
Colonic Neoplasms
Butyric Acid
Caspase 9
Cell death
Colorectal Neoplasms
Cell Death
Epithelial Cells
Peptides
Proteins

Keywords

  • Bcl-2
  • Butyrate
  • Caspase
  • Colorectal carcinoma
  • Differentiation
  • Mitochondria

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Role of caspase activation in butyrate-induced terminal differentiation of HT29 colon carcinoma cells. / Cai, Jiyang; Chen, Yan; Murphy, T. J.; Jones, Dean P.; Sartorelli, Alan C.

In: Archives of Biochemistry and Biophysics, Vol. 424, No. 2, 15.04.2004, p. 119-127.

Research output: Contribution to journalArticle

Cai, Jiyang ; Chen, Yan ; Murphy, T. J. ; Jones, Dean P. ; Sartorelli, Alan C. / Role of caspase activation in butyrate-induced terminal differentiation of HT29 colon carcinoma cells. In: Archives of Biochemistry and Biophysics. 2004 ; Vol. 424, No. 2. pp. 119-127.
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