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.

Acknowledgments

The author wishes to thank Dr. T. Kiyoi (Advanced Research Support Center, Ehime University) for histological examination.

Data Availability Statement

Raw data supporting the conclusions of the present study will be made available by the author, without undue reservation, to any qualified researcher.

Ethics Statement

Research involving animals was performed according to Ethical Guidelines for Animal Experimentation by Ehime University and the Japanese Pharmacological Society based on the Act on Welfare and Management of Animals [Article 41 (1–4)] published by the Ministry of the Environment of Japan and The Guide for the Care and Use of Laboratory Animals published by the National Institute of Health (NIH), USA.

Disclosure statement

The author declares that this research was conducted in the absence of any commercial or financial relationships that may be construed as a potential conflict of interest.

Funding

This work was supported by the JSPS KAKENHI Grant Number JP20K07804, Japan (A respective: Yoshiyuki Kimura).