Tiliroside Combined with Anti-MUC1 Monoclonal Antibody as Promising Anti-Cancer Strategy in AGS Cancer Cells

Int J Mol Sci. 2023 Aug 22;24(17):13036. doi: 10.3390/ijms241713036.

Abstract

Specific changes in mucin-type O-glycosylation are common for many cancers, including gastric ones. The most typical alterations include incomplete synthesis of glycan structures, enhanced expression of truncated O-glycans (Tn, T antigens and their sialylated forms), and overexpression of fucosylation. Such altered glycans influence many cellular activities promoting cancer development. Tiliroside is a glycosidic dietary flavonoid with pharmacological properties, including anti-cancer. In this study, we aim to assess the effect of the combined action of anti-MUC1 and tiliroside on some cancer-related factors in AGS gastric cancer cells. Cancer cells were treated with 40, 80, and 160 µM tiliroside, 5 µg/mL anti-MUC1, and flavonoid together with mAb. Real-Time PCR, ELISA, and Western blotting were applied to examine MUC1 expression, specific, tumor-associated antigens, enzymes taking part in their formation, Gal-3, Akt, and NF-κB. MUC1 expression was significantly reduced by mAb action. The combined action of anti-MUC1 and tiliroside was more effective in comparison with monotherapy in the case of C1GalT1, ST3GalT1, FUT4, Gal-3, NF-κB, Akt mRNAs, and Tn antigen, as well as sialyl T antigen expression. The results of our study indicate that applied combined therapy may be a promising anti-gastric cancer strategy.

Keywords: MUC1; TACAs; gastric cancer; glycoforms; tiliroside.

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Flavonoids
  • Fucosyltransferases
  • Humans
  • Mucin-1 / immunology
  • NF-kappa B*
  • Proto-Oncogene Proteins c-akt
  • Stomach Neoplasms* / immunology
  • Stomach Neoplasms* / therapy

Substances

  • Antibodies, Monoclonal
  • Flavonoids
  • Fucosyltransferases
  • FUT4 protein, human
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • tiliroside
  • Mucin-1