3'-Hydroxypterostilbene Suppresses Colitis-Associated Tumorigenesis by Inhibition of IL-6/STAT3 Signaling in Mice

J Agric Food Chem. 2017 Nov 8;65(44):9655-9664. doi: 10.1021/acs.jafc.7b03712. Epub 2017 Oct 31.

Abstract

3'-Hydroxypterostilbene (trans-3,5-dimethoxy-3',4'-hydroxystilbene) presents in Sphaerophysa salsula, Pterocarpus marsupium, and honey bee propolis and has been reported to exhibit several biological activities. Herein, we aimed to explore the chemopreventive effects of dietary 3'-hydroxypterostilbene and underlying molecular mechanisms on colitis-associated cancer using the azoxymethane (AOM)/dextran sodium sulfate (DSS) model. 3'-Hydroxypterostilbene administration effectively ameliorated the colon shortening and number of tumors in AOM/DSS-treated mice (3.2 ± 1.2 of the high-dose treatment versus 13.8 ± 5.3 of the AOM/DSS group, p < 0.05). Molecular analysis exhibited the anti-inflammatory activity of 3'-hydroxypterostilbene by a significant decrease in the levels of inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-6 (IL-6) (p < 0.05). Moreover, dietary 3'-hydroxypterostilbene also significantly diminished IL-6/signal transducer and activator of transcription signaling and restored colonic suppressor of cytokine signaling 3 levels in the colonic tissue of mice (p < 0.05). Collectively, these results demonstrated for the first time the in vivo chemopreventive efficacy and molecular mechanisms of dietary 3'-hydroxypterostilbene against colitis-associated colonic tumorigenesis.

Keywords: 3′-hydroxypterostilbene; azoxymethane; colitis; dextran sodium sulfate; inflammation.

MeSH terms

  • Animals
  • Anticarcinogenic Agents / administration & dosage*
  • Carcinogenesis / drug effects*
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Colitis / complications*
  • Colitis / genetics
  • Colitis / metabolism
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / prevention & control*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Stilbenes / administration & dosage*

Substances

  • 3'-hydroxypterostilbene
  • Anticarcinogenic Agents
  • Interleukin-6
  • STAT3 Transcription Factor
  • Stilbenes
  • Cyclooxygenase 2