TY - JOUR TI - Dihydroxystilbenes prevent azoxymethane/dextran sulfate sodium-induced colon cancer by inhibiting colon cytokines, a chemokine, and programmed cell death-1 in C57BL/6J mice AU - Kimura, Yoshiyuki AU - Sumiyoshi, Maho AU - Kiyoi, Takeshi AU - Baba, Kimiye T2 - European Journal of Pharmacology AB - The incidence of colon cancer increased worldwide in 2019 and its treatment is urgent from a quality of life perspective. A relationship has been reported between elevated numbers of tumor-associated macrophages (TAMs) in the tumor microenvironment and a poor prognosis in cancer patients, and M2 TAMs have been shown to promote tumor growth by immunosuppression through the stimulation of programmed death-1 (PD-1, an immune check point receptor), interleukin (IL)-1β, and monocyte chemoattractant protein (MCP)-1. We herein examined the effects of three synthetic dihydroxystilbenes (2,3-, 3,4-, and 4,4′-dihydroxystilbenes) on colon carcinogenesis, colon tumor growth, and colon cytokines (IL-1β, IL-6, and tumor necrosis factor (TNF)-α), a chemokine (MCP-1), vascular endothelial growth factor (VEGF), and PD-1 levels in azoxymethane (AOM) plus dextran sulfate sodium (DSS)-treated C57BL/6J mice. The three dihydroxystilbenes inhibited colon carcinogenesis and tumor growth as well as increases in colon IL-1β, IL-6, MCP-1, and PD-1 levels in AOM/DDS-treated mice (in vivo). The three dihydroxystilbenes also suppressed COX-2 expression in colon tumors (in vivo). The results obtained also revealed that the three dihydroxystilbenes inhibited PD-1 elevations in M2-THP-1 macrophages (in vitro). Therefore, the inhibition of AOM/DSS-induced colon carcinogenesis and colon tumor growth by 2,3-, 3,4-, and 4,4′-dihydroxystilbenes appears to be due to the suppression of M2 TAM differentiation and activation and PD-1 expression (immunosuppression) via reductions in COX-2 expression levels in the colon tumor microenvironment. DA - 2020/08/03/ PY - 2020 DO - 10.1016/j.ejphar.2020.173445 DP - ScienceDirect SP - 173445 J2 - European Journal of Pharmacology LA - en SN - 0014-2999 UR - http://www.sciencedirect.com/science/article/pii/S0014299920305379 Y2 - 2020/08/07/20:00:25 KW - Colon cancer KW - Dihydroxystilbenes KW - IL-1β KW - M2 macrophages KW - PD-1 ER -