Increased Sulfiredoxin Expression in Gastric Cancer Cells May Be a Molecular Target of the Anticancer Component Diallyl Trisulfide

Biomed Res Int. 2019 Feb 4:2019:4636804. doi: 10.1155/2019/4636804. eCollection 2019.

Abstract

Sulfiredoxin (Srx) is a newly discovered antioxidant enzyme playing a role in the catalytic reduction of oxidative modifications. Srx is overexpressed in a variety of cancers. It may promote carcinogenesis as well as tumor progression. In this study, we report for the first time that Srx expression might be positively associated with the development of gastric cancer and tumor malignancy. Immunohistochemistry showed that, compared to normal tissues (42%, 20/47), Srx expression in gastric tumors (85%, 40/47) was much more common (chi-square test, p<0.01). In addition, the staining of Srx was stronger in poorly differentiated gastric cancer than in well-differentiated gastric cancer. Western blotting showed that, in the gastric tumor cell line BGC823, the Srx protein was upregulated in response to H2O2 treatment, although it was inadequate to counteract the increased oxidative stress, as indicated by the gradually increasing level of malondialdehyde (MDA). In addition, Srx expression, MDA levels, and ROS levels in BGC823 cells were markedly inhibited upon treatment with diallyl trisulfide (DATS), a major constituent of garlic oil with proven anticancer effects. These results suggest that Srx may be an oxidative stress marker. Antioxidation may account for the anticancer potential of garlic.

MeSH terms

  • Allyl Compounds / chemistry
  • Allyl Compounds / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Garlic / chemistry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hydrogen Peroxide / toxicity
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects*
  • Oxidoreductases Acting on Sulfur Group Donors / genetics*
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Sulfides / chemistry
  • Sulfides / pharmacology*

Substances

  • Allyl Compounds
  • Antioxidants
  • Sulfides
  • diallyl trisulfide
  • Malondialdehyde
  • Hydrogen Peroxide
  • Oxidoreductases Acting on Sulfur Group Donors
  • SRXN1 protein, human