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Journal of Toxicology
Volume 2009 (2009), Article ID 785907, 14 pages
Research Article

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

1Department of Cell Biology & Anatomy, College of Medicine, University of Arizona, Tucson, AZ 85724-5044, USA
2Arizona Cancer Center, University of Arizona, Tucson, AZ 85724-5044, USA
3INCELL Corporation, San Antonio, TX 78249, USA
4Department of Internal Medicine, College of Medicine, University of Arizona, Tucson, AZ 85724-5044, USA
5Southern Arizona Veterans Affairs Health Care System, Tucson, AZ 85723, USA

Received 18 September 2008; Revised 25 January 2009; Accepted 24 February 2009

Academic Editor: Brad Upham

Copyright © 2009 Claire M. Payne et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We report that deoxycholate (DOC), a hydrophobic bile acid associated with a high-fat diet, activates the autophagic pathway in non-cancer colon epithelial cells (NCM-460), and that this activation contributes to cell survival. The DOC-induced increase in autophagy was documented by an increase in autophagic vacuoles (detected using transmission electron microscopy, increased levels of LC3-I and LC3-II (western blotting), an increase in acidic vesicles (fluorescence spectroscopy of monodansycadaverine and lysotracker red probes), and increased expression of the autophagic protein, beclin-1 (immunohistochemistry/western blotting). The DOC-induced increase in beclin-1 expression was ROS-dependent. Rapamycin (activator of autophagy) pre-treatment of NCM-460 cells significantly ( ) decreased, and 3-MA (inhibitor of autophagy) significantly ( ) increased the cell loss caused by DOC treatment, alone. Rapamycin pre-treatment of the apoptosis-resistant colon cancer cell line, HCT-116RC (developed in our laboratory), resulted in a significant decrease in DOC-induced cell death. Bafilomycin and hydroxychloroquine (inhibitors of the autophagic process) increased the DOC-induced percentage of apoptotic cells in HCT-116RC cells. It was concluded that the activation of autophagy by DOC has important implications for colon carcinogenesis and for the treatment of colon cancer in conjunction with commonly used chemotherapeutic agents.