title: Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress.
abstract: BACKGROUND
  Ion channel modulators have been previously associated with cell proliferation and cell death in human cancer cell lines.
  
  
  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.
  
  
  CONCLUSIONS
  Riluzole induces inhibition of DNA synthesis and apoptotic cell death via ER stress in both the LNCaP and C4-2 prostate cancer cell lines.
authors.affiliation: Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Akamatsu
authors.forename: Masa-Aki
authors.initials: MA
authors.lastname: Shibata
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ito
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Sohma
authors.forename: Haruhito
authors.initials: H
authors.lastname: Azuma
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Otsuki
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D019782:Riluzole / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D061945:Caspase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole; D045304:Cytochromes c; D020169:Caspases