Document Detail


Ceramide promotes the death of human cervical tumor cells in the absence of biochemical and morphological markers of apoptosis.
MedLine Citation:
PMID:  12051763     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
C8-ceramide, a synthetic cell-permeable analog of endogenous ceramides, interfered with cell proliferation, and was cytotoxic to papilloma virus-containing human cervix carcinoma cells, CALO, INBL, and HeLa, that match two clinical stages of tumor progression. C8-ceramide (3 microM) markedly reduced the tumor cell number after 48 h of treatment, an effect that endured even after the removal of C8-ceramide. The carcinoma cells showed morphologic changes, characteristic of necrosis and released lactate dehydrogenase (LDH). A biologically inactive analog C8-dihydro-ceramide had no effect on cell viability in any of the cell lines tested. Seventy-two hours after C8-ceramide treatment none of the biochemical and morphological markers characteristic of apoptosis: (a) nuclear chromatin condensation, (b) DNA fragmentation, (c) proteolysis of the caspase-3 substrate poly-(ADP-ribose)-polymerase (PARP), and (d) appearance of phosphatidylserine on the external cell membrane, were observed. C8-ceramide had no effect on human cervix fibroblasts and induced a mild reduction (30%) in the proliferation of normal human cervix epithelia and HeLa cells (IV-B metastatic stage). The cytotoxicity of C8-ceramide was restricted to CALO (early II-B) and INBL (IV-A non-metastatic) carcinoma cells. The possible application of ceramide in the treatment of early stages of cervical cancer is discussed.
Authors:
Rebeca López-Marure; Gisela Gutiérrez; Criselda Mendoza; José Luis Ventura; Luis Sánchez; Elba Reyes Maldonado; Alejandro Zentella; Luis Felipe Montaño
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  293     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-06-07     Completed Date:  2002-06-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1028-36     Citation Subset:  IM    
Copyright Information:
(c) 2002 Elsevier Science (USA).
Affiliation:
Departamento de Biología Celular, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1, Colonia Sección 16, Tlalpan, C.P. 14080, Mexico DF, Mexico. rmarure@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis*
Biological Markers / analysis
Carcinoma / chemistry,  drug therapy*,  pathology
Cell Death
Cell Division / drug effects
Cells, Cultured
Ceramides / pharmacology*
Cervix Uteri / drug effects
Dose-Response Relationship, Drug
Female
Hela Cells
Humans
L-Lactate Dehydrogenase / analysis
Tumor Cells, Cultured
Uterine Cervical Neoplasms / chemistry,  drug therapy*,  pathology
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Biological Markers; 0/Ceramides; EC 1.1.1.27/L-Lactate Dehydrogenase

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