Carcinogenesis Advance Access published online on August 3, 2006
Carcinogenesis, doi:10.1093/carcin/bgl139
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Cell Biology & Anatomy, College of Medicine, University of Arizona; Arizona Cancer Center, University of Arizona
* To whom correspondence should be addressed. NF-
Received March 17, 2006
Revised July 11, 2006
Accepted July 19, 2006
CARCINOGENESIS
Deoxycholate induces mitochondrial oxidative stress and activates NF-
C. M. Payne 1 *, C. Weber 2, C. Crowley-Skillicorn 2, K. Dvorak 1, H. Bernstein 1, C. Bernstein 2, H. Holubec 2, B. Dvorakova 2, and H. Garewal 3
B through multiple mechanisms in HCT-116 colon epithelial cells
2 Department of Cell Biology & Anatomy, College of Medicine, University of Arizona
3 Arizona Cancer Center, University of Arizona; Department of Internal Medicine, College of Medicine, University of Arizona; Southern Arizona Veterans Affairs Health Care System
C. M. Payne, E-mail: cpayne{at}email.arizona.edu
Abstract 
B is a redox-associated transcription factor that is involved in the activation of survival pathways. We have previously shown that DOC activates NF-B in hepatocytes and colon epithelial cells and that persistent exposure of HCT-116 cells to increasing concentrations of DOC results in the constitutive activation of NF-B, which is associated with the development of apoptosis resistance. The mechanisms by which DOC activates NF-B in colon epithelial cells, and whether natural antioxidants can reduce DOC-induced NF-B activation, however, are not known. Also, it is not known if DOC can generate ROS within mitochondria as a possible pathway of stress-related NF-B activation. Since we have previously shown that DOC activates the NF-B stress-response pathway in HCT-116 cells, we used this cell line to further explore the mechanisms of NF-B activation. We found that DOC induces mitochondrial oxidative stress and activates NF-B in HCT-116 cells through multiple mechanisms involving NAD(P)H oxidase, Na+/K+-ATPase, cytochrome P450, Ca++ and the terminal mitochondrial respiratory complex IV. DOC-induced NF-B activation was significantly (p<0.05) inhibited by pre-treatment of cells with CAPE, EGCG, TMS, DPI, NaN3, EGTA, Ouabain and RuR. The NF-B-activating pathways, induced by the dietary-related endogenous detergent DOC, provide mechanisms for promotion of colon cancer and identify possible new targets for chemoprevention.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. W. Katona, S. Anant, D. F. Covey, and W. F. Stenson Characterization of Enantiomeric Bile Acid-induced Apoptosis in Colon Cancer Cell Lines J. Biol. Chem., January 30, 2009; 284(5): 3354 - 3364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. S. Jenkins, J. Cronin, A. Alhamdani, N. Rawat, F. D'Souza, T. Thomas, Z. Eltahir, A. P. Griffiths, and J. N. Baxter The bile acid deoxycholic acid has a non-linear dose response for DNA damage and possibly NF-{kappa}B activation in oesophageal cells, with a mechanism of action involving ROS Mutagenesis, September 1, 2008; 23(5): 399 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dvorak, M. Chavarria, C. M. Payne, L. Ramsey, C. Crowley-Weber, B. Dvorakova, B. Dvorak, H. Bernstein, H. Holubec, R. E. Sampliner, et al. Activation of the Interleukin-6/STAT3 Antiapoptotic Pathway in Esophageal Cells by Bile Acids and Low pH: Relevance to Barrett's Esophagus Clin. Cancer Res., September 15, 2007; 13(18): 5305 - 5313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Dvorak, C. M Payne, M. Chavarria, L. Ramsey, B. Dvorakova, H. Bernstein, H. Holubec, R. E Sampliner, N. Guy, A. Condon, et al. Bile acids in combination with low pH induce oxidative stress and oxidative DNA damage: relevance to the pathogenesis of Barrett's oesophagus Gut, June 1, 2007; 56(6): 763 - 771. [Abstract] [Full Text] [PDF]
|
|