+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Activation and role of mitogen-activated protein kinases in deoxycholic acid-induced apoptosis



Activation and role of mitogen-activated protein kinases in deoxycholic acid-induced apoptosis



Carcinogenesis 22(1): 35-41



The bile acid deoxycholic acid (DCA) is a known tumor promoter and it has been suggested that DCA-induced apoptosis plays an important role in colon tumor development. In this study we have characterized the capacity of DCA to stimulate mitogen-activated protein kinase (MAPK) activity and examined the effect that MAPK activity had on DCA-induced apoptosis. Analysis of MAPK activity in DCA-treated HCT116 cells using phosphorylation-specific antibodies and in vitro kinase assays indicated that both the extracellular signal-regulated kinase (ERK) and p38 MAPK (p38), but not the c-Jun N-terminal kinase (JNK), were activated. Using pharmacological inhibitors we determined that only ERK could influence DCA cytotoxicity and that elevated ERK activity could suppress DCA-induced apoptosis. This observation was confirmed genetically. Suppressing ERK activity by overexpressing a dominant negative form of the ERK MAP kinase resulted in increased sensitivity to DCA-induced apoptosis whereas elevated ERK activity artificially produced by overexpression of the wild-type ERK kinase blunted DCA-induced apoptosis. Taken together, our results suggest that DCA can stimulate pro-apoptotic and anti-apoptotic signaling pathways and that sensitivity to DCA-induced apoptosis can be modulated by the ERK MAP kinase.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010119582

Download citation: RISBibTeXText

PMID: 11159738

DOI: 10.1093/carcin/22.1.35


Related references

Role of mitogen-activated protein kinases in activation-induced apoptosis of T cells. Immunology 97(1): 26-35, 1999

Docosahexaenoic acid-induced apoptosis is mediated by activation of mitogen-activated protein kinases in human cancer cells. Bmc Cancer 14: 481, 2014

Differential activation of MAPK and ICE/Ced-3 protease in chemical-induced apoptosis. The role of oxidative stress in the regulation of mitogen-activated protein kinases (MAPKs) leading to gene expression and survival or activation of caspases leading to apoptosis. Restorative Neurology and Neuroscience 12(2-3): 63-70, 1998

Butylated hydroxyanisole and its metabolite tert-butylhydroquinone differentially regulate mitogen-activated protein kinases. The role of oxidative stress in the activation of mitogen-activated protein kinases by phenolic antioxidants. Journal of Biological Chemistry 272(46): 28962-28970, 1997

Role of the mitogen-activated protein kinases in neutrophil activation and apoptosis. Surgical Forum 48: 33-35, 1997

Deoxycholic acid causes ligand-independent activation of epidermal growth factor receptor and FAS receptor in primary hepatocytes Inhibition of EGFR/mitogen-activated protein kinase-signaling module enhances DCA-induced apoptosis. Molecular Biology of the Cell 12(9): 2609-2645, 2001

Role of the mitogen-activated protein kinases and tyrosine kinases during leukotriene B4-induced eosinophil activation. Journal of Leukocyte Biology 64(4): 555-562, 1998

Prolonged activation of mitogen-activated protein kinases in NSAIDs-induced apoptosis. Gastroenterology 118(4 Suppl 2 Part 1): AGA A535, 2000

Role of mitogen-activated protein kinases and tyrosine kinases on IL-1-Induced NF-kappaB activation and iNOS expression in bovine articular chondrocytes. Nitric Oxide 6(1): 35-44, 2002

Deoxycholic acid (DCA) causes ligand-independent activation of epidermal growth factor receptor (EGFR) and FAS receptor in primary hepatocytes: inhibition of EGFR/mitogen-activated protein kinase-signaling module enhances DCA-induced apoptosis. Molecular Biology of the Cell 12(9): 2629-2645, 2001

Role of mitogen-activated protein kinases in S-nitrosoglutathione-induced macrophage apoptosis. Biochemistry 38(8): 2279-2286, 1999

Role of mitogen-activated protein kinases in salicylate-induced apoptosis of eosinophils. Clinical Chemistry & Laboratory Medicine 37(SPEC Suppl. ): S489, 1999

Prolonged activation of mitogen-activated protein kinases during NSAID-induced apoptosis in HT-29 colon cancer cells. International Journal of Colorectal Disease 16(3): 167-173, 2001