Document Detail

Normalization of sphingomyelin levels by 2-hydroxyoleic acid induces autophagic cell death of SF767 cancer cells.
MedLine Citation:
PMID:  22892762     Owner:  NLM     Status:  MEDLINE    
The very high mortality rate of gliomas reflects the unmet therapeutic need associated with this type of brain tumor. We have discovered that the plasma membrane fulfills a critical role in the propagation of tumorigenic signals, whereby changes in membrane lipid content can either activate or silence relevant pathways. We have designed a synthetic fatty acid, 2-hydroxyoleic acid (2OHOA), that specifically activates sphingomyelin synthase (SGMS), thereby modifying the lipid content of cancer cell membranes and restoring lipid levels to those found in normal cells. In reverting, the structure of the membrane by activating SGMS, 2OHOA inhibits the RAS-MAPK pathway, which in turn fails to activate the CCND (Cyclin D)-CDK4/CDK6 and PI3K-AKT1 pathways. The overall result in SF767 cancer cells, a line that is resistant to apoptosis, is the sequential induction of cell cycle arrest, cell differentiation and autophagy. Such effects are not observed in normal cells (MRC-5) and thus, this specific activation of programmed cell death infers greater efficacy and lower toxicity to 2OHOA than that associated with temozolomide (TMZ), the reference drug for the treatment of glioma.
Silvia Terés; Victoria Lladó; Mónica Higuera; Gwendolyn Barceló-Coblijn; M Laura Martin; Maria Antònia Noguera-Salvà; Amaia Marcilla-Etxenike; José Manuel García-Verdugo; Mario Soriano-Navarro; Carlos Saus; Ulises Gómez-Pinedo; Xavier Busquets; Pablo V Escribá
Publication Detail:
Type:  Journal Article     Date:  2012-08-15
Journal Detail:
Title:  Autophagy     Volume:  8     ISSN:  1554-8635     ISO Abbreviation:  Autophagy     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-26     Revised Date:  2013-10-01    
Medline Journal Info:
Nlm Unique ID:  101265188     Medline TA:  Autophagy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1542-4     Citation Subset:  IM    
Molecular Cell Biomedicine, Department of Biology-IUNICS, University of the Balearic Islands, Palma de Mallorca, Spain.
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MeSH Terms
Autophagy / drug effects*
Cell Cycle / drug effects
Cell Line, Tumor
Endoplasmic Reticulum Stress / drug effects
Glioma / pathology*
Models, Biological
Oleic Acids / pharmacology*
Signal Transduction / drug effects
Sphingomyelins / metabolism*
Reg. No./Substance:
0/2-hydroxyoleic acid; 0/Oleic Acids; 0/Sphingomyelins

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

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