Long-Term Oral Administration of Piceatannol (3,5,3′,4′-Tetrahydroxystilbene) Attenuates Colon Tumor Growth Induced by Azoxymethane Plus Dextran Sulfate Sodium in C57BL/6J Mice

Abstract

Aim: The effects of 3,5,3′,4′-tetrahydroxystilbene (piceatannol) on azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colon cancer growth and changes in IL-1β, IL-6, tumor necrosis factor-α (cytokines), MCP-1, vascular endothelial growth factor, and PD-1 colon levels were investigated herein. Methods: AOM (10 mg/kg, i.p.) on day 0 induced colorectal carcinogenesis. On day 3, mice were provided with water containing 1.5% (w/v) DSS ad libitum for 3 day, and this 3-day drinking protocol was repeated twice. Piceatannol (5 and 12.5 mg/kg, twice daily) was orally administered to mice for 7-, 7-, 7-, and 6-day and then discontinued for 14-, 15-, and 16-day. Cytokines, chemokine, and PD-1 colon levels were measured by the respective ELISA kits. Results: In mice administered piceatannol (12.5 mg/kg), the tumor number, tumor area, and Ki-67-positive cell numbers decreased by 30.1%, 57.2%, and 89.1%, respectively, colon MCP-1 and PD-1 levels showed reductions of 43.8% and 70.9%, respectively, and COX-2-positive cell numbers declined by 60.2%. Conclusions: The inhibitory effects of piceatannol on AOM/DSS-induced colon tumor growth appear to be associated with reductions in colon MCP-1 and PD-1 levels through the downregulated expression of COX-2 in the tumor microenvironment.