Rosmarinic acid influences collagen, MMPs, TIMPs, glycosylation and MUC1 in CRL-1739 gastric cancer cell line

Biomed Pharmacother. 2018 Nov;107:397-407. doi: 10.1016/j.biopha.2018.07.123. Epub 2018 Aug 9.

Abstract

Rosmarinic acid (RA) is a natural phenylpropanoid with numerous pharmacological activities. Because of limited studies of the effects of RA action in gastric cancer cells we examined how 100 and 200 μM acid influences MMPs, TIMPs, collagen, MUC1 and specific sugar antigens in gastric adenocarcinoma CRL-1739 cells. We revealed inhibitory effect of RA on MMP-9 activity what was correlated with increased collagen type I expression, main ECM substrate degraded by MMPs. Tissue inhibitor of MMPs, TIMP-1 but not TIMP-2 was significantly decreased on the protein level and increased on mRNA level by RA action what can suggest TIMP-1 independent inhibitory action of an acid on MMP-9 activity. Glycosylation of gastric cancer proteins was also effected by RA. ELISA tests revealed inhibitory effect of an acid on Tn antigen in cell lysates and culture supernatant and on T antigen in cell lysates. RA inhibited also sialylated Tn antigen in protein of culture supernatant and sialyl T in cell lysates. Extracellular domain of MUC1 mucin, main carrier of Tn and T antigens was significantly inhibited by higher dose of RA. The data suggest potential usefulness of RA as a complementary agent supporting chemotherapy in cancer treatment.

Keywords: Collagen; Glycosylation; MMPs; MUC1; Rosmarinic acid; TIMPs.

MeSH terms

  • Antigens / metabolism
  • Cell Line, Tumor
  • Cinnamates / chemistry
  • Cinnamates / pharmacology*
  • Collagen / metabolism*
  • Depsides / chemistry
  • Depsides / pharmacology*
  • Glycosylation
  • Humans
  • Matrix Metalloproteinases / metabolism*
  • Mucin-1 / metabolism*
  • Stomach Neoplasms / enzymology
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tissue Inhibitor of Metalloproteinases / metabolism*

Substances

  • Antigens
  • Cinnamates
  • Depsides
  • Mucin-1
  • Tissue Inhibitor of Metalloproteinases
  • Collagen
  • Matrix Metalloproteinases
  • rosmarinic acid