Document Detail


Inhibition of tetraphenylphosphonium-induced NMR-visible lipid accumulation in human breast cells by chlorpromazine.
MedLine Citation:
PMID:  14499734     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of chlorpromazine (CPZ) on the lipid accumulation induced by the cationic lipophilic compound tetraphenylphosphonium chloride (TPP) were examined using proton nuclear magnetic resonance spectroscopy (NMR), lipid extraction and thin layer chromatography (TLC), and electron microscopy (EM). Chlorpromazine at concentrations of 12 or 25 microM significantly reduced the NMR-visible lipid accumulation induced by a 48-h treatment with 6.25 microM TPP in the human breast cell line, HBL-100, without affecting cell viability. TPP caused threefold increases in whole-cell triglyceride levels that were attenuated by the addition of CPZ. Electron micrographs of TPP-treated HBL-100 cells showed that the destruction of mitochondria was accompanied by the accumulation of lipid droplets and myelinoid bodies. The addition of CPZ to TPP-treated cells reduced the occurrence of lipid droplets but not of mitochondrial destruction. Treatment with CPZ, in the presence or absence of TPP, resulted in large cytoplasmic inclusions indicating the inhibition of lysosomal metabolism. The induction and attenuation of NMR-visible lipids in conjunction with concomitant changes in both intracellular lipid droplets and whole-cell triglyceride levels provides evidence that NMR-visible lipids arise from cytoplasmic neutral lipid droplets. The observation that CPZ, a known inhibitor of lysosomal and cytosolic lipid metabolism, attenuates the formation of neutral triglycerides indicates that lysosomal processing may be a major step in the accumulation of NMR-visible lipid in breast cell lines.
Authors:
Nalayini Sathasivam; Susan Brammah; Lesley C Wright; Edward J Delikatny
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1633     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-22     Completed Date:  2003-11-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  149-60     Citation Subset:  IM    
Affiliation:
Department of Cancer Medicine, Blackburn Building, D06, University of Sydney, NSW 2006, Australia.
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MeSH Terms
Descriptor/Qualifier:
Breast / cytology,  drug effects*,  metabolism*
Cell Line
Chlorpromazine / administration & dosage,  pharmacology*
Dose-Response Relationship, Drug
Drug Interactions
Female
Humans
Lipid Metabolism*
Lysosomes / drug effects,  metabolism,  ultrastructure
Magnetic Resonance Spectroscopy
Microscopy, Electron
Onium Compounds / administration & dosage,  pharmacology*
Organophosphorus Compounds / administration & dosage,  pharmacology*
Triglycerides / metabolism
Grant Support
ID/Acronym/Agency:
R21 CA79718/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Onium Compounds; 0/Organophosphorus Compounds; 0/Triglycerides; 18198-39-5/tetraphenylphosphonium; 50-53-3/Chlorpromazine

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


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