Akamatsu Kanako, Shibata Masa-Aki, Ito Yuko, Sohma Yoshiro, Azuma Haruhito, Otsuki Yoshinori
Department of Anatomy and Cell Biology, Division of Life Sciences, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Anticancer Res. 2009 Jun;29(6):2195-204.
Ion channel modulators have been previously associated with cell proliferation and cell death in human cancer cell lines.
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.
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.
Riluzole induces inhibition of DNA synthesis and apoptotic cell death via ER stress in both the LNCaP and C4-2 prostate cancer cell lines.
离子通道调节剂先前已被证明与人类癌细胞系中的细胞增殖和细胞死亡有关。
研究了离子通道调节剂利鲁唑对LNCaP和C4-2前列腺癌细胞系中细胞增殖、凋亡及凋亡途径的影响。
利鲁唑抑制了两种细胞系中的DNA合成并增加了凋亡细胞。半胱天冬酶-3、-8和-9的活性显著增加，并且针对半胱天冬酶-3、-8和-9的半胱天冬酶抑制剂显著挽救了用利鲁唑处理的两种癌细胞系的细胞活力。然而，在用利鲁唑处理的细胞中未观察到线粒体膜电位的变化、细胞色素c的释放和Bid的裂解。利鲁唑显著诱导半胱天冬酶-4活性升高、荧光表明胞质钙升高以及通过透射电子显微镜观察到的内质网（ER）形态变化。
利鲁唑通过内质网应激诱导LNCaP和C4-2前列腺癌细胞系中的DNA合成抑制和凋亡细胞死亡。
