TY - JOUR
T1 - The indole compound MA-35 attenuates tumorigenesis in an inflammation-induced colon cancer model
AU - Kanehara, Keigo
AU - Ohnuma, Shinobu
AU - Kanazawa, Yoshitake
AU - Sato, Keisuke
AU - Kokubo, Shoji
AU - Suzuki, Hideyuki
AU - Karasawa, Hideaki
AU - Suzuki, Takehiro
AU - Suzuki, Chitose
AU - Naitoh, Takeshi
AU - Unno, Michiaki
AU - Abe, Takaaki
N1 - Funding Information:
We thank the following people. Emiko Shibuya and Keiko Inabe (Department of Surgery, Tohoku University Graduate School of Medicine) for technical supports. This work was supported in part by the Japan Society for the Promotion of Science KAKENHI Grant Numbers 18H02822 (T.A.), 30547401 (H.K.), 18K16339 (H.S.), 18K08669 (T.N.) and 16H05410 (M.U.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071760133&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85071760133&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-48974-9
DO - 10.1038/s41598-019-48974-9
M3 - Article
C2 - 31484999
AN - SCOPUS:85071760133
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12739
ER -
