Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells

Differential activation of PKC and MAP kinases

L. McMillan, S. K. Butcher, J. Pongrácz, J. M. Lord

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Butyrate, produced in the colon by fermentation of dietary fibre, induces apoptosis in colon adenoma and cancer cell lines, which may contribute to protection against colorectal cancer. However, butyrate is present in the colon along with other dietary factors, including unconjugated bile acids, which are tumour promoters. We have shown previously that the proapoptotic effects of butyrate on AA/Cl human adenoma cells were reduced in the presence of bile acids. To determine the cellular basis of this interaction, we examined the effects of butyrate and the secondary bile acid ursodeoxycholic acid (UDCA) on signalling pathways known to regulate apoptosis using AA/Cl cells. Butyrate activated PKC-δ and p38 MAP (mitogen-activated protein) kinase, whereas UDCA activated PKC-α and p42/44 MAP kinase. Butyrate treatment also resulted in the caspase-3-mediated proteolysis of PKC-δ. Butyrate-induced apoptosis was reduced by inhibitors of PKC-δ (Rottlerin), p38 MAP kinase (SB202190) and caspase 3 (DEVD-fmk), whereas the proliferative/survival effects of UDCA were blocked by inhibitors of PKC-α (Gö6976) and MEK I (PD98059). The effects of butyrate and bile acids are therefore mediated by the differential activation of signalling pathways that are known to regulate apoptosis.

Original languageEnglish
Pages (from-to)748-753
Number of pages6
JournalBritish Journal of Cancer
Volume88
Issue number5
DOIs
Publication statusPublished - Mar 10 2003

Fingerprint

Butyrates
Mitogen-Activated Protein Kinases
Bile Acids and Salts
Adenoma
Colon
Apoptosis
Ursodeoxycholic Acid
p38 Mitogen-Activated Protein Kinases
Caspase 3
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Dietary Fiber
Carcinogens
Colonic Neoplasms
Proteolysis
Fermentation
Colorectal Neoplasms
Cell Line
Survival

Keywords

  • Apoptosis
  • Bile acids
  • Butyrate
  • Colon adenoma cancer
  • MAP kinase
  • PKC

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells : Differential activation of PKC and MAP kinases. / McMillan, L.; Butcher, S. K.; Pongrácz, J.; Lord, J. M.

In: British Journal of Cancer, Vol. 88, No. 5, 10.03.2003, p. 748-753.

Research output: Contribution to journalArticle

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