| Title | Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress. | | Author(s) | Akamatsu K, Shibata MA, Ito Y, Sohma Y, Azuma H, Otsuki Y | | Institution | Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. | | Source | Anticancer Res 2009 Jun; 29(6):2195-204. | | Abstract | 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. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19528481 |
|