Differential regulation of EGFR-MAPK signaling by deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) in colon cancer.

Sara M Centuori, Jesse D Martinez

Journal: Digestive diseases and sciences 2014;59(10):2367-80

PMID: 25027205

Abstract

A high-fat diet coincides with increased levels of bile acids. This increase in bile acids, particularly deoxycholic acid (DCA), has been strongly associated with the development of colon cancer. Conversely, ursodeoxycholic acid (UDCA) may have chemopreventive properties. Although structurally similar, DCA and UDCA present different biological and pathological effects in colon cancer progression. The differential regulation of cancer by these two bile acids is not yet fully understood. However, one possible explanation for their diverging effects is their ability to differentially regulate signaling pathways involved in the multistep progression of colon cancer, such as the epidermal growth factor receptor (EGFR)-mitogen-activated protein kinase (MAPK) pathway. This review will examine the biological effects of DCA and UDCA on colon cancer development, as well as the diverging effects of these bile acids on the oncogenic signaling pathways that play a role in colon cancer development, with a particular emphasis on bile acid regulation of the EGFR-MAPK pathway.

Address: Department of Cellular and Molecular Medicine, The University of Arizona Cancer Center, 1515 N. Campbell Ave., PO Box 245024, Tucson, AZ, 85724-5024, USA, [email protected].
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