Document Detail


Head and neck cancer cell lines are resistant to mitochondrial-depolarization-induced apoptosis.
MedLine Citation:
PMID:  18483464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Mitochondrial dysfunction has been linked to defects in the apoptotic pathway, and solid tumors, including head and neck squamous cell carcinoma (HNSCC), exhibit defects in apoptosis. Loss of mitochondrial membrane potential (DeltaPsim) is an early initiating event in the mitochondrial apoptotic pathway. We investigated the apoptotic response of 3 head and neck cancer cell lines treated with a mitochondrial-membrane-depolarizing agent, valinomycin, and studied the ability of depolarization to induce release of cytochrome c in these cell lines. EXPERIMENTAL DESIGN: HNSCC cell lines JHU-011, -012 and -019, and a leukemia control cell line HL-60 were assayed for DeltaPsim after valinomycin treatment by staining with mitochondrial-membrane-potential-specific probe JC-1 and stained with apoptosis-specific probe annexin-V to measure their rate of apoptosis by FACS. Western blotting was also applied to detect cytoplasmic cytochrome c release. RESULTS: DeltaPsim in head and neck cell lines started to show slight loss of DeltaPsim, while HL-60 showed significant loss of DeltaPsim after 30 min of treatment. All cell lines demonstrated complete mitochondrial depolarization within 24 h, however, only the control cell line HL-60 underwent apoptosis. In addition, HNSCC cell lines did not demonstrate cytoplasmic cytochrome c release despite significant mitochondrial membrane depolarization, while HL-60 cell initiated apoptosis and cytochcrome c release after 24 h of treatment. CONCLUSIONS: Head and neck cancer cell lines exhibit defects in mitochondrial-membrane-depolarization-induced apoptosis as well as impaired release of cytochrome c despite significant mitochondrial membrane depolarization. Proximal defects in the mitochondrial apoptosis pathway are a feature of HNSCC.
Authors:
Ming Zhao; Wojciech K Mydlarz; Shaoyu Zhou; Joseph Califano
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2008-05-16
Journal Detail:
Title:  ORL; journal for oto-rhino-laryngology and its related specialties     Volume:  70     ISSN:  1423-0275     ISO Abbreviation:  ORL J. Otorhinolaryngol. Relat. Spec.     Publication Date:  2008  
Date Detail:
Created Date:  2008-06-20     Completed Date:  2008-08-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0334721     Medline TA:  ORL J Otorhinolaryngol Relat Spec     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  257-63     Citation Subset:  IM    
Copyright Information:
Copyright 2008 S. Karger AG, Basel.
Affiliation:
Department of Otolaryngology, Head and Neck Surgery, Johns Hopkins Medical Institution, Baltimore, MD 21287-0910, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology*
Blotting, Western
Carcinoma, Squamous Cell / metabolism,  pathology*
Cell Line, Tumor
Cytochromes c / biosynthesis
Flow Cytometry
Head and Neck Neoplasms / metabolism,  pathology*
Humans
Membrane Potential, Mitochondrial / physiology*
Mitochondria / metabolism*,  pathology
Chemical
Reg. No./Substance:
9007-43-6/Cytochromes c

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


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