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 journalArticle

21 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

Fingerprint

Riluzole
Endoplasmic Reticulum Stress
Prostatic Neoplasms
Cell Death
Cell Line
Caspase 8
Ion Channels
Caspase 3
Cell Proliferation
Caspase Inhibitors
Mitochondrial Membrane Potential
DNA
Caspases
Cytochromes c
Transmission Electron Microscopy
Endoplasmic Reticulum
Cell Survival
Fluorescence
Apoptosis
Calcium

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Akamatsu, K., Shibata, M. A., Ito, Y., Sohma, Y., Azuma, H., & Otsuki, Y. (2009). Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress. Anticancer Research, 29(6), 2195-2204.

Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress. / Akamatsu, Kanako; Shibata, Masa Aki; Ito, Yuko; Sohma, Yoshiro; Azuma, Haruhito; Otsuki, Yoshinori.

In: Anticancer Research, Vol. 29, No. 6, 06.2009, p. 2195-2204.

Research output: Contribution to journalArticle

Akamatsu, K, Shibata, MA, Ito, Y, Sohma, Y, Azuma, H & Otsuki, Y 2009, 'Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress', Anticancer Research, vol. 29, no. 6, pp. 2195-2204.
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. Anticancer Research. 2009 Jun;29(6):2195-2204.
Akamatsu, Kanako ; Shibata, Masa Aki ; Ito, Yuko ; Sohma, Yoshiro ; Azuma, Haruhito ; Otsuki, Yoshinori. / Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress. In: Anticancer Research. 2009 ; Vol. 29, No. 6. pp. 2195-2204.
@article{c172b7579b7848b78685baadfa5383b1,
title = "Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress",
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.",
keywords = "Apoptosis, Endoplasmic reticulum stress, Ion channel, Prostate cancer, Riluzole",
author = "Kanako Akamatsu and Shibata, {Masa Aki} and Yuko Ito and Yoshiro Sohma and Haruhito Azuma and Yoshinori Otsuki",
year = "2009",
month = "6",
language = "English",
volume = "29",
pages = "2195--2204",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "6",

}

TY - JOUR

T1 - Riluzole induces apoptotic cell death in human prostate cancer cells via endoplasmic reticulum stress

AU - Akamatsu, Kanako

AU - Shibata, Masa Aki

AU - Ito, Yuko

AU - Sohma, Yoshiro

AU - Azuma, Haruhito

AU - Otsuki, Yoshinori

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Endoplasmic reticulum stress

KW - Ion channel

KW - Prostate cancer

KW - Riluzole

UR - http://www.scopus.com/inward/record.url?scp=67650901985&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650901985&partnerID=8YFLogxK

M3 - Article

C2 - 19528481

AN - SCOPUS:67650901985

VL - 29

SP - 2195

EP - 2204

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 6

ER -