Akamatsu K, Shibata MA, Ito Y, Sohma Y, Azuma H, Otsuki Y
Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress. [Journal Article]
Anticancer Res 2009 Jun; 29(6):2195-204.
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.
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