Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress.
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.
Akamatsu
Kanako
K
Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Shibata
Masa-Aki
MA
Ito
Yuko
Y
Sohma
Yoshiro
Y
Azuma
Haruhito
H
Otsuki
Yoshinori
Y
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
D061945:Caspase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole; D045304:Cytochromes c; D020169:Caspases