Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds

Masato Takahashi, Tomonori Sato, Fumiaki Shinohara, Seishi Echigo, Hidemi Rikiishi

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

Abstract

Selenium (Sc) is a very effective anti-cancer agent. We studied the effects of inorganic Sc compounds on induction of apoptosis by which Se compounds exert cancer chemopreventive activity. With the use of HSC-3 human oral squamous cell carcinoma cells, the present study showed that treatment with Sc for 72 h, in the form of SeO2 and Na2SeO3, but not Na 2SeO4, markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 μM SeO2 resulted in the caspasc-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (ΔΨm), but did not induce the generation of reactive oxygen species. Treatment with SeO2 for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Sc. Treatment with N-acctyl-L-cysteinc, or exogenous GSH, prevented the SeO2-induced apoptosis. Treatment with GSH led to the partial reverse in reduction of ΔΨm caused by SeO2 while buthionine sulfoximine augmented the SeO2- or Na2SeO 3- induced apoptosis. These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspasc-9-mediated apoptosis without a concurrent increase in ROS.

Original languageEnglish
Pages (from-to)489-495
Number of pages7
JournalInternational journal of oncology
Volume27
Issue number2
Publication statusPublished - 2005 Aug 1

Keywords

  • Apoptosis
  • Glutathione
  • Mitochondria
  • Oral squamous cell carcinoma
  • Selenium

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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