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Deoxycholate, an Endogenous CytotoxinGenotoxin, Induces the Autophagic Stress-Survival Pathway : Implications for Colon Carcinogenesis
Joint Authors
Garewal, Harinder
Dvorak, Katerina
Payne, Claire M.
Bernstein, Carol
Crowley-Skillicorn, Cheray
Bernstein, Harris
Moyer, Mary Pat
Holubec, Hana
Source
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-05-10
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Pharmacy, Health & Medical Sciences
Medicine
Abstract EN
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 (P<.05) decreased, and 3-MA (inhibitor of autophagy) significantly (P<.05) 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 A1 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.
American Psychological Association (APA)
Payne, Claire M.& Crowley-Skillicorn, Cheray& Holubec, Hana& Dvorak, Katerina& Bernstein, Carol& Moyer, Mary Pat…[et al.]. 2009. Deoxycholate, an Endogenous CytotoxinGenotoxin, Induces the Autophagic Stress-Survival Pathway : Implications for Colon Carcinogenesis. Journal of Toxicology،Vol. 2009, no. 2009, pp.1-14.
https://search.emarefa.net/detail/BIM-497962
Modern Language Association (MLA)
Payne, Claire M.…[et al.]. Deoxycholate, an Endogenous CytotoxinGenotoxin, Induces the Autophagic Stress-Survival Pathway : Implications for Colon Carcinogenesis. Journal of Toxicology No. 2009 (2009), pp.1-14.
https://search.emarefa.net/detail/BIM-497962
American Medical Association (AMA)
Payne, Claire M.& Crowley-Skillicorn, Cheray& Holubec, Hana& Dvorak, Katerina& Bernstein, Carol& Moyer, Mary Pat…[et al.]. Deoxycholate, an Endogenous CytotoxinGenotoxin, Induces the Autophagic Stress-Survival Pathway : Implications for Colon Carcinogenesis. Journal of Toxicology. 2009. Vol. 2009, no. 2009, pp.1-14.
https://search.emarefa.net/detail/BIM-497962
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-497962