Document Detail

Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress.
MedLine Citation:
PMID:  19528481     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Ion channel modulators have been previously associated with cell proliferation and cell death in human cancer cell lines. MATERIALS AND METHODS: The effects of riluzole, an ion channel modulator, on cell proliferation, apoptosis and the apoptotic pathway in the LNCaP and C4-2 prostate cancer cell lines were investigated. RESULTS: Riluzole inhibited DNA synthesis and increased apoptotic cells in both cell lines. The activities of caspase-3, -8 and -9 were significantly increased, and caspase inhibitors for caspase-3, -8 and -9 significantly rescued the cell viability of both carcinoma cell lines treated with riluzole. However, a change in mitochondrial membrane potential, release of cytochrome c and cleavage of Bid were not observed in the riluzole-treated cells. Riluzole significantly induced elevation of caspase-4 activity, fluorescence indicating cytosolic calcium, and morphological changes in endoplasmic reticulum (ER) as observed by transmission electron microscopy. CONCLUSION: Riluzole induces inhibition of DNA synthesis and apoptotic cell death via ER stress in both the LNCaP and C4-2 prostate cancer cell lines.
Kanako Akamatsu; Masa-Aki Shibata; Yuko Ito; Yoshiro Sohma; Haruhito Azuma; Yoshinori Otsuki
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  29     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-16     Completed Date:  2009-09-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  2195-204     Citation Subset:  IM    
Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
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MeSH Terms
Apoptosis / drug effects*
Caspases / antagonists & inhibitors,  metabolism
Cell Proliferation / drug effects
Cytochromes c / metabolism
Endoplasmic Reticulum / metabolism*,  pathology
Excitatory Amino Acid Antagonists / pharmacology*
Membrane Potential, Mitochondrial / drug effects
Prostatic Neoplasms / drug therapy*,  metabolism,  pathology*
Riluzole / pharmacology*
Signal Transduction / drug effects
Tumor Cells, Cultured
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 1744-22-5/Riluzole; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspases

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