Cell death induction by isothiocyanates and their underlying molecular mechanisms

Yoshimasa Nakamura, Noriyuki Miyoshi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

An important and promising group of compounds that have a chemopreventive property are organosulfur compounds, such as isothiocyanates (ITCs). In recent years, it has been shown that ITCs induce apoptosis in various cancer cell lines and experimental rodents. During the course of apoptosis induction by ITC, multiple signal-transduction pathways and apoptosis intermediates are modulated. We have also clarified the molecular mechanism underlying the relationship between cell cycle arrest and apoptosis induced by benzyl isothiocyanate (BITC), a major ITC compound isolated from papaya. The exposure of cells to BITC resulted in the inhibition of the G2/M progression that coincided with not only the up-regulated expression of the G2/M cell cycle arrest-regulating genes but also the apoptosis induction. The experiment using the phase-specific synchronized cells demonstrated that the G2/M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We identified the phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with the JNK activation by BITC. We also found that BITC induced the cytotoxic effect more preferentially in the proliferating normal human colon epithelial cells than in the quiescent cells. Conversely, treatment with an excessive concentration of BITC resulted in necrotic cell death without DNA ladder formation. This review addresses the biological impact of cell death induction by BITC as well as other ITCs and the involved signal transduction pathways.

Original languageEnglish
Pages (from-to)123-134
Number of pages12
JournalBioFactors
Volume26
Issue number2
DOIs
Publication statusPublished - 2006

Fingerprint

Isothiocyanates
Cell death
Cell Death
Apoptosis
Cells
Signal transduction
Cell Cycle Checkpoints
Signal Transduction
G2 Phase Cell Cycle Checkpoints
Carica
G2 Phase
Ladders
p38 Mitogen-Activated Protein Kinases
benzyl isothiocyanate
Cell Division
Rodentia
Colon
Genes
Epithelial Cells
Chemical activation

Keywords

  • Apoptosis
  • Benzyl isothiocyanate
  • Cell cycle arrest
  • MAP kinase
  • Necrosis

ASJC Scopus subject areas

  • Biochemistry

Cite this

Cell death induction by isothiocyanates and their underlying molecular mechanisms. / Nakamura, Yoshimasa; Miyoshi, Noriyuki.

In: BioFactors, Vol. 26, No. 2, 2006, p. 123-134.

Research output: Contribution to journalArticle

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