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

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-? (TNF-?) signaling. In addition, intestinal fibrosis is a common clinical complication that is promoted by transforming growth factor ?1 (TGF-?₁). In our previous study, MA-35 attenuated renal fibrosis by inhibiting both TNF-? and TGF-?₁ 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-? mRNA level in the colon tended to be reduced, and the interleukin 6, TGF-?₁ 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.

SUBMITTER: Kanehara K 

PROVIDER: S-EPMC6726640 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature