Chemopreventive effects of synthetic C-substituted diindolylmethanes originating from cruciferous vegetables in human oral cancer cells

Ji Ae Shin, Jung Hyun Shim, Eun Sun Choi, Dae Ho Leem, Ki Han Kwon, Syng Ook Lee, Stephen Safe, Nam Pyo Cho, Sung Dae Cho

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Diindolylmethane (DIM), an isothiocyanate found in cruciferous vegetables, has been shown to have cancer chemopreventive effects. A series of synthetic C-substituted DIMs (C-DIMs) analogs was developed, including DIM-C-pPhtBu and DIM-C-pPhC 6H 5, which exhibited better inhibitory activity in cancer cells than DIM. This study examined the effects of C-DIMs on the growth of human oral cancer cells. DIM-C-pPhtBu and DIM-C-pPhC 6H 5 decreased the number of viable KB cells and induced caspase-dependent apoptosis. The apoptotic cell death was accompanied by a change in Bax/Bcl-2 ratio and damage to mitochondrial membrane potential through the induction of death receptor 5 and the cleavage of Bid and caspase 8. Studies on the mechanism of action showed that the apoptotic cell death induced by DIM-C-pPhtBu and DIM-C-pPhC 6H 5 was mediated by endoplasmic reticulum stress. In addition, C-DIMs inhibited cell proliferation and induced PARP cleavage through death receptor 5 and CHOP in HEp-2 and HN22 cells. This provides the first evidence that synthetic C-DIMs originating from cruciferous vegetables induce apoptosis in human oral cancer cells through the endoplasmic reticulum stress pathway.

Original languageEnglish (US)
Pages (from-to)417-425
Number of pages9
JournalEuropean Journal of Cancer Prevention
Volume20
Issue number5
DOIs
StatePublished - Sep 2011

Keywords

  • apoptosis
  • C-substituted diindolylmethane
  • death receptor 5
  • endoplasmic reticulum stress
  • human oral cancer cell
  • mitochondrial membrane potential

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

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