Deoxycholate, an Endogenous Cytotoxin/Genotoxin, Induces the Autophagic Stress-Survival Pathway: Implications for Colon Carcinogenesis

Figure 8

Diagram indicating the possible roles of autophagy in colon carcinogenesis. Hydrophobic bile acids are known to induce numerous stresses in colon epithelial cells that result in the activation of prosurvival stress-response pathways. NF-κB activation by hydrophobic bile acids induces prosurvival pathways. The present study reports that deoxycholate (DOC), a hydrophobic bile acid that is important in colon carcinogenesis, activates autophagy. This activation of autophagy by DOC was also shown to have a prosurvival function. The constitutive upregulation of prosurvival pathways (resulting from chronic exposure to DOC and selection for apoptosis resistance) can enhance mutation rates, which may lead to the development of colon cancer. NCM-460 and HCT- 116RC cells were used as model cell lines to evaluate the bile acid-induced activation of the autophagic pathway and its consequences in the early and late stages of colon carcinogenesis, respectively.