The indole compound MA-35 attenuates tumorigenesis in an inflammation-induced colon cancer model

Sci Rep. 2019 Sep 4;9(1):12739. doi: 10.1038/s41598-019-48974-9.

Abstract

In inflammatory bowel disease, chronic inflammation results in the development of colon cancer known as colitis-associated cancer. This disease is associated with tumor necrosis factor-α (TNF-α) signaling. In addition, intestinal fibrosis is a common clinical complication that is promoted by transforming growth factor β1 (TGF-β1). In our previous study, MA-35 attenuated renal fibrosis by inhibiting both TNF-α and TGF-β1 signaling. This study aimed to identify the possible antitumor effects and antifibrotic effects of MA-35 using an AOM/DSS mouse model. MA-35 was orally administered every day for 70 days in the AOM/DSS mouse model. There was no difference in weight loss between the AOM/DSS group and the AOMDSS + MA-35 group, but the disease activity index score and the survival rate were improved by MA-35. MA-35 blocked the anemia and shortening of the colon induced by AOM/DSS. MA-35 reduced the macroscopic formation of tumors in the colon. In the microscopic evaluation, MA-35 reduced inflammation and fibrosis in areas with dysplasia. Furthermore, the TNF-α mRNA level in the colon tended to be reduced, and the interleukin 6, TGF-β1 and fibronectin 1 mRNA levels in the colon were significantly reduced by MA-35. These results suggested that MA-35 inhibited AOM/DSS-induced carcinogenesis by reducing inflammation and fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / chemically induced
  • Carcinogenesis / drug effects
  • Carcinogenesis / genetics
  • Carcinogenesis / immunology
  • Colonic Neoplasms / chemically induced
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / immunology*
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Fibronectins / genetics
  • Fibronectins / immunology
  • Humans
  • Indoles / administration & dosage*
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Male
  • Mice
  • Mice, Inbred ICR
  • Transforming Growth Factor beta1 / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Fibronectins
  • Indoles
  • Interleukin-6
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate