Antioxidant effects of sulforaphane in human HepG2 cells and immortalised hepatocytes

Peng Liu, Wei Wang, Jonathan Tang, Richard P Bowater, Yongping Bao (Corresponding Author)

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Sulforaphane (SFN) has shown anti-cancer effects in cellular and animal studies but its effectiveness has been limited in human studies. Here, the effects of SFN were measured in both human hepatocytes (HHL5) and hepatoma (HepG2) cells. Results showed that SFN inhibited cell viability and induced DNA strand breaks at high doses (≥20 μM). It also activated the nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and increased intracellular glutathione (GSH) levels at 24 h. Pre-treatment with a low dose SFN (≤5 μM) protected against hydrogen peroxide (H2O2)-induced cell damage. High doses of SFN were more toxic towards HHL5 compared to HepG2 cells; the difference is likely due to the disparity in the responses of Nrf2-driven enzymes and -GSH levels between the two cell lines. In addition, HepG2 cells hijacked the cytoprotective effect of SFN over a wider dose range (1.25-20 μM) compared to HHL5. Manipulation of levels of GSH and Nrf2 in HepG2 cells confirmed that both molecules mediate the protective effects of SFN against H2O2. The non-specific nature of SFN in the regulation of cell death and survival could present undesirable risks, i.e. be more toxic to normal cells, and cause chemo-resistance in tumor cells. These issues should be addressed in the context for cancer prevention and treatment before large scale clinical trials are undertaken.

Original languageEnglish
Pages (from-to)129-136
Number of pages8
JournalFood and Chemical Toxicology
Volume128
Early online date30 Mar 2019
DOIs
Publication statusPublished - Jun 2019

    Fingerprint

Keywords

  • Antioxidants/administration & dosage
  • Cell Line, Transformed
  • Cell Survival/drug effects
  • DNA/drug effects
  • Dose-Response Relationship, Drug
  • Glutathione/metabolism
  • Hep G2 Cells
  • Humans
  • Hydrogen Peroxide/toxicity
  • Isothiocyanates/administration & dosage
  • NF-E2-Related Factor 2/genetics
  • Oxidative Stress/drug effects
  • RNA, Small Interfering/genetics
  • Oxidative stress
  • Hepatocyte
  • Nrf2
  • Chemopreventive
  • Sulforaphane
  • GSH
  • TARGET
  • APOPTOSIS
  • ISOTHIOCYANATE
  • PANCREATIC-CANCER
  • CYCLE ARREST
  • KEAP1-NRF2 PATHWAY
  • NRF2
  • OXIDATIVE STRESS
  • BROCCOLI
  • GLUTATHIONE

Cite this