Document Detail


Lysophosphatidic acid inhibits anti-Fas-mediated apoptosis enhanced by actin depolymerization in epithelial ovarian cancer.
MedLine Citation:
PMID:  15710431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Conflicting reports exist on the effect of actin depolymerization in anti-Fas-induced apoptosis. Lysophosphatidic acid (LPA) has been found to inhibit apoptosis in variable cell types. In this study, we evaluated LPA's protective effects on anti-Fas-induced apoptosis enhanced by actin depolymerization and possible mechanisms in epithelial ovarian cancer. OVCAR3 cells were pretreated with vehicle or LPA, then treated with Cytochalasin D (Cyto D), followed with anti-Fas mAb to induce apoptosis. Cells were stained with apoptotic markers and analyzed by flow cytometry. We report that LPA inhibited anti-Fas-induced apoptosis enhanced by actin depolymerization. Immunoprecipition of Fas death-inducing signaling complex (DISC) and Western blot suggested that the actin depolymerization accelerated caspase-8 activation, while LPA inhibited the association and activation of caspase-8 at the DISC. LPA inhibited caspase-3 and 7 activation induced by anti-Fas and/or Cyto D in cytosols. Phosphorylation of ERK and Bad112 by LPA may play a role in preventing caspase-3 activation through mitochondrial pathway induced by Cyto D. Our investigation found that LPA inhibited anti-Fas-induced apoptosis enhanced by actin depolymerization, and LPA may protect epithelial ovarian cancer from immune cell attack and cytoskeleton disrupting reagents induced apoptosis through multiple pathways.
Authors:
Yuru Meng; Shijun Kang; David A Fishman
Publication Detail:
Type:  Journal Article     Date:  2005-01-26
Journal Detail:
Title:  FEBS letters     Volume:  579     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  2005 Feb 
Date Detail:
Created Date:  2005-02-15     Completed Date:  2005-04-05     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1311-9     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, and R H Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL 60611, USA. ruthmwk@yahoo.com
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MeSH Terms
Descriptor/Qualifier:
Actins / metabolism*
Antibodies / immunology
Antigens, CD95 / immunology,  metabolism*
Apoptosis / drug effects*
Carrier Proteins / metabolism
Caspases / antagonists & inhibitors,  metabolism
Cell Line, Tumor
Cytochalasin D / pharmacology
Cytoskeleton / drug effects,  metabolism
Down-Regulation / drug effects
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Epithelial Cells / drug effects*,  metabolism,  pathology*
Extracellular Signal-Regulated MAP Kinases / metabolism
Female
Humans
Lysophospholipids / pharmacology*
Ovarian Neoplasms / metabolism*,  pathology*
Phosphorylation / drug effects
bcl-Associated Death Protein
Chemical
Reg. No./Substance:
0/Actins; 0/Antibodies; 0/Antigens, CD95; 0/BAD protein, human; 0/Carrier Proteins; 0/Enzyme Inhibitors; 0/Lysophospholipids; 0/bcl-Associated Death Protein; 22002-87-5/lysophosphatidic acid; 22144-77-0/Cytochalasin D; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 3.4.22.-/Caspases

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