Document Detail


Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents.
MedLine Citation:
PMID:  16565487     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-beta cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs.
Authors:
Ying Chun Li; Mi Jung Park; Sang-Kyu Ye; Chul-Woo Kim; Yong-Nyun Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The American journal of pathology     Volume:  168     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-03-27     Completed Date:  2006-05-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1107-18; quiz 1404-5     Citation Subset:  AIM; IM    
Affiliation:
Division of Specific Organs Cancer, Pediatric Oncology Division, National Cancer Center, 809 Madu 1-dong, Ilsan-gu, Goyang-si, Gyeonggi-do 411-769, Korea.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / drug effects,  physiology*
Breast Neoplasms
Carcinoma, Squamous Cell
Caspase 3
Caspases / metabolism
Cell Line, Tumor
Cell Survival
Cholesterol / metabolism*
Down-Regulation
Enzyme Activation
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
Male
Membrane Microdomains / drug effects,  metabolism*
Neoplasms / metabolism,  pathology*,  ultrastructure
Prostatic Neoplasms
Proto-Oncogene Proteins c-akt / metabolism
Receptor, Epidermal Growth Factor / metabolism
Signal Transduction
Simvastatin / pharmacology
bcl-X Protein / metabolism
beta-Cyclodextrins / pharmacology*
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/bcl-X Protein; 0/beta-Cyclodextrins; 0/methyl-beta-cyclodextrin; 57-88-5/Cholesterol; 79902-63-9/Simvastatin; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases
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