Effects of sulforaphane on the oxidative response, apoptosis, and the transcriptional profile of human stomach mucosa cells in vitro

Mutat Res Genet Toxicol Environ Mutagen. 2020 Jun-Jul:854-855:503201. doi: 10.1016/j.mrgentox.2020.503201. Epub 2020 May 31.

Abstract

Oxidative stress is a critical factor in the pathogenesis of several gastrointestinal diseases. Sulforaphane (SFN), a bioactive compound found in cruciferous vegetables, activates the redox-sensitive nuclear erythroid 2-related factor 2 (NRF2). In addition to its protective role, SFN exerts cytotoxic effects on cancer cells. However, there is a lack of information concerning the toxicity of SFN in normal cells. We investigated the effects of SFN on cell viability, antioxidant defenses, and gene expression in human stomach mucosa cells (MNP01). SFN reduced ROS formation and protected the cells against induced oxidative stress but high concentrations increased apoptosis. An intermediate SFN concentration (8 μM) was chosen for RNA sequencing studies. We observed upregulation of genes of the NRF2 (antioxidant) pathway, the DNA damage response, and apoptosis signaling; whereas SFN downregulated cell cycle and DNA repair pathway genes. SFN may be cytoprotective at low concentrations and cytotoxic at high concentrations.

Keywords: Antioxidant; Cytoprotective; Isothiocyanate; Nutrigenomics; Sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / pharmacology
  • Antioxidants / pharmacology
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Survival / drug effects
  • Humans
  • Isothiocyanates / pharmacology*
  • Mucous Membrane / drug effects*
  • Mucous Membrane / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Stomach / drug effects*
  • Sulfoxides
  • Transcription, Genetic / drug effects*
  • Up-Regulation / drug effects

Substances

  • Anticarcinogenic Agents
  • Antioxidants
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Sulfoxides
  • sulforaphane