Ursodeoxycholic Acid (UDCA) Can Inhibit Deoxycholic Acid (DCA)-induced Apoptosis via Modulation of EGFR/Raf-1/ERK Signaling in Human Colon Cancer Cells

Eunok Im, Jesse D. Martinez

Research output: Contribution to journalArticlepeer-review

131 Scopus citations

Abstract

Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, is known as a cytoprotective agent. UDCA prevents apoptosis induced by a variety of stress stimuli including cytotoxic bile acids such as deoxycholic acid (DCA). Here we examined the molecular mechanism by which UDCA can antagonize DCA-induced apoptosis in human colon cancer cells. UDCA pretreatment decreases the number of apoptotic cells caused by exposure to DCA and UDCA. Further studies of the signaling pathway showed that UDCA pretreatment suppressed DNA binding activity of activator protein-1 and this was accompanied by downregulation of both extracellular signal-regulated kinase (ERK) and Raf-1 kinase activities stimulated by exposure to DCA. DCA was also found to activate epidermal growth factor receptor (EGFR) activity and UDCA inhibited this. Collectively, these findings suggest that the inhibitory effect of UDCA in DCA-induced apoptosis is partly mediated by modulation of EGFR/Raf-1/ERK signaling.

Original languageEnglish (US)
Pages (from-to)483-486
Number of pages4
JournalJournal of Nutrition
Volume134
Issue number2
DOIs
StatePublished - Feb 2004

Keywords

  • Apoptosis
  • Colon cancer
  • Deoxycholic acid
  • Ursodeoxycholic acid

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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