Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress

Kanako Akamatsu, Masa Aki Shibata, Yuko Ito, Yoshiro Sohma, Haruhito Azuma, Yoshinori Otsuki

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2195-2204
Number of pages10
JournalAnticancer research
Volume29
Issue number6
Publication statusPublished - 2009 Jun 1

Keywords

  • Apoptosis
  • Endoplasmic reticulum stress
  • Ion channel
  • Prostate cancer
  • Riluzole

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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