Document Detail


Inhibition of autophagy potentiates sulforaphane-induced apoptosis in human colon cancer cells.
MedLine Citation:
PMID:  19830499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Sulforaphane (SUL), an isothiocyanate naturally present in widely consumed vegetables, particularly broccoli, has recently attracted attention due to its inhibitory effects on tumor cell growth by inducing apoptosis. We investigated the ability of SUL to induce autophagy in human colon cancer cells and whether inhibition of autophagy could potentiate the proapoptotic effect of SUL. METHODS: The proliferation of cells treated with SUL was assessed by MTS assay and colony-forming assay. Apoptosis and caspases activity were investigated by flow cytometry. The formation of acidic vesicular organelles (AVOs) was detected in acridine-orange-stained cells by flow cytometry. Western blotting was used for the detection of light chain 3 (LC3). Localizations of LC3 and cytochrome c were analyzed by immunocytochemistry. RESULTS: The proapoptotic effect was observed by treatment of cells with relatively high concentrations of SUL for long periods of time. After 16 h of treatment, evident formation of AVOs and recruitment of LC3 to autophagosomes, features of autophagy, were observed. Treatment of cells with a specific autophagy inhibitor (3-methyladenine) potentiated the proapoptotic effect of SUL, which was dependent on the activation of caspases and the release of cytochrome c to the cytosol. CONCLUSION: The present results demonstrate induction of autophagy in colon cancer cells as a protective reaction against the proapoptotic effect of SUL, and consequently, the potentiation of the proapoptotic effect by autophagy inhibition. These findings provide a premise for use of autophagy inhibitors in combination with chemotherapeutic agents for treatment of colorectal cancer.
Authors:
Takeshi Nishikawa; Nelson H Tsuno; Yurai Okaji; Yasutaka Shuno; Kazuhito Sasaki; Kumiko Hongo; Eiji Sunami; Joji Kitayama; Koki Takahashi; Hirokazu Nagawa
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Publication Detail:
Type:  Journal Article     Date:  2009-10-15
Journal Detail:
Title:  Annals of surgical oncology     Volume:  17     ISSN:  1534-4681     ISO Abbreviation:  Ann. Surg. Oncol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-05     Completed Date:  2010-05-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9420840     Medline TA:  Ann Surg Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  592-602     Citation Subset:  IM    
Affiliation:
Department of Surgical Oncology, Faculty of Medical Science, The University of Tokyo, Tokyo, Japan. takn-tky@umin.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Adenine / analogs & derivatives,  pharmacology
Anticarcinogenic Agents / pharmacology*
Apoptosis / drug effects*
Autophagy / drug effects*
Blotting, Western
Caspases / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Colonic Neoplasms / drug therapy*,  pathology*
Colony-Forming Units Assay
Cytochromes c / metabolism
Flow Cytometry
Humans
Thiocyanates / pharmacology*
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Thiocyanates; 4478-93-7/sulforafan; 5142-23-4/3-methyladenine; 73-24-5/Adenine; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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