Protective effect of sulforaphane on indomethacin-induced cytotoxicity via heme oxygenase-1expression in human intestinal Int 407 cells

Chi Tai Yeh, Hsiang Fan Chiu, Gow Chin Yen

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Sulforaphane is known to be an indirect antioxidant that acts by inducing NF-E2-related factor 2 (Nrf2)-dependent phase II enzymes. In the present study, we investigated the effect of sulforaphane on the expression of heme oxygenase-1 (HO-1) in human intestinal Int 407 cells. RT-PCR and West- ern blot data revealed that sulforaphane induced an increase in HO-1 expression at the mRNA and protein levels, respectively. This induction was also marked by an increase in HO-1 activity. Actino- mycin D (an RNA synthesis inhibitor) and cycloheximide (a protein synthesis inhibitor) inhibited sul- foraphane-responsive HO-1 mRNA expression, indicating that sulforaphane is a requirement for tran- scription and de novo protein synthesis. Moreover, sulforaphane increased the nuclear levels of Nrf2 and increased the binding activity of nuclear proteins to the antioxidant responsive element consensus sequence. We also found that U0126, an ERK kinase inhibitor, suppressed the sulforaphane-induced HO-1 expression and nuclear translocation of Nrf2. Moreover, the cytoprotective effect of sulfora- phane on indomethancin-induced cytotoxicity was partially blocked by ERK and HO-1 inhibitors, fur- ther demonstrating that sulforaphane attenuated oxidative stress through a pathway that involved ERK and HO-1. Taken together, this study gives additional support to the possible use of sulforaphane as a dietary preventive agent against oxidative stress-induced intestinal injury.

Original languageEnglish
Pages (from-to)1166-1176
Number of pages11
JournalMolecular Nutrition and Food Research
Volume53
Issue number9
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Heme oxygenase
  • Indomethacin
  • Intestinal Int 407 cells
  • Nonsteroidal anti-inflammatory drugs
  • Sulforaphane

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

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