Dietary Ziziphus jujuba Fruit Attenuates Colitis-Associated Tumorigenesis: A Pivotal Role of the NF-κB/IL-6/JAK1/STAT3 Pathway

Nutr Cancer. 2020;72(1):120-132. doi: 10.1080/01635581.2019.1615515. Epub 2019 May 28.

Abstract

Inflammatory bowel disease (IBD) including ulcerative colitis (UC) is one of the risk factors for the development of colitis-associated colon cancer (CAC). CAC is a type of colorectal cancer (CRC), the third leading cause of cancer death. Ziziphus jujuba (ZJ) fruit contains bioactive components such as polysaccharides, triterpenoid acid, and flavonoids, and it has shown anti-inflammatory property. The aim of the study was to investigate the protective effect of dietary ZJ on colitis-associated colorectal tumorigenesis in mice. Mice (n = 42, two sets) were injected with azoxymethane (AOM) followed by three cycles of 2% (w/v) dextran sulfate sodium (DSS) in drinking water to induce CAC. Simultaneously, those mice were fed with ZJ diet for 70 days (5% or 10% w/w). Data were analyzed by ANOVA followed by LSD Bonferroni test. Dietary ZJ decreased fecal blood, diarrhea, disease activity index (DAI), spleen weight (P < 0.001), and the number of tumors (P < 0.001). In addition, dietary ZJ increased colon length (P < 0.001) and suppressed the activation of NF-кB/IL-6/JAK1/STAT3 signaling pathway. In conclusion, we suggest that dietary ZJ attenuates inflammation by interfering NF-κB/IL-6/JAK1/STAT3 signaling pathway, thereby inhibits AOM/DSS-induced colon tumorigenesis in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azoxymethane / toxicity
  • Carcinogens / toxicity
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • Chemoprevention
  • Colitis / chemically induced
  • Colitis / complications*
  • Colitis / pathology
  • Colonic Neoplasms / diet therapy*
  • Colonic Neoplasms / etiology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Fruit / chemistry
  • Interleukin-6 / metabolism*
  • Janus Kinase 1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Plant Extracts / pharmacology*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Transcription Factor RelA / metabolism*
  • Ziziphus / chemistry*

Substances

  • Carcinogens
  • Interleukin-6
  • Plant Extracts
  • Rela protein, mouse
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Transcription Factor RelA
  • interleukin-6, mouse
  • Jak1 protein, mouse
  • Janus Kinase 1
  • Azoxymethane