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

Keigo Kanehara, Shinobu Ohnuma, Yoshitake Kanazawa, Keisuke Sato, Shoji Kokubo, Hideyuki Suzuki, Hideaki Karasawa, Takehiro Suzuki, Chitose Suzuki, Takeshi Naitoh, Michiaki Unno, Takaaki Abe

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number12739
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • General

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