Co-administration of 5FU and propolis on AOM/DSS induced colorectal cancer in BALB-c mice

Life Sci. 2021 Jul 1:276:119390. doi: 10.1016/j.lfs.2021.119390. Epub 2021 Mar 29.

Abstract

Aims: Currently, the main problems with chemotherapy are its side effects, toxicity, and drug resistance. Propolis has biological activities, such as anti-inflammatory and anti-cancer properties. This study aims to examine the combined effects of 5-fluorouracil (5FU) and propolis on colorectal cancer (CRC) in mouse models.

Materials and methods: The chemical composition of ethanolic extract of propolis was determined by gas chromatography-mass spectrometry (GC-MS). In this study, 49 male Balb/c mice (16-20 g) were divided in seven groups as a control group and experimental groups (treated and untreated CRC model [azoxymethane + dextran sodium sulfate]). This study was conducted in 8 weeks. To examine the anti-cancer effects of propolis, the number of aberrant crypt foci (ACF) was counted and the pathological lesions in the distal colonic epithelial tissue were diagnosed. In this study, the expression of beta-catenin (β-catenin), induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) proteins, which play a major role in the incidence and progression of cancer, were determined.

Key findings: GC-MS analysis of propolis showed the presence of hydrocarbons, alcohols, ketones, terpenes, phenols, and flavonoids. Administering propolis in combination with 5FU reduced the number of ACFs and pathological lesions in comparison with cancer control groups (p < 0.0001) and 5FU-alone treatment (p < 0.05). The propolis combined with 5FU reduced the expression of Cox-2, iNOS, and β-catenin proteins.

Significance: The results showed that propolis increased the efficiency of 5FU and could be taken into account as the adjunct therapy for colorectal cancer.

Keywords: Azoxymethane; Catenins; Colorectal neoplasms; Fluorouracil; Mice; Nitric oxide synthase type II; Propolis.

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology*
  • Antimetabolites, Antineoplastic / pharmacology*
  • Azoxymethane / toxicity*
  • Carcinogens / toxicity
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Dextran Sulfate / toxicity*
  • Drug Therapy, Combination
  • Fluorouracil / pharmacology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Propolis / pharmacology*

Substances

  • Anti-Infective Agents
  • Antimetabolites, Antineoplastic
  • Carcinogens
  • Propolis
  • Dextran Sulfate
  • Azoxymethane
  • Fluorouracil