Propolis Enhances 5-Fluorouracil Mediated Antitumor Efficacy and Reduces Side Effects in Colorectal Cancer: An in Vitro and in Vivo Study

Chem Biodivers. 2023 Sep;20(9):e202300591. doi: 10.1002/cbdv.202300591. Epub 2023 Aug 8.


In this study, we investigated the combined treatment of 5-fluorouracil (5-FU) and Anatolian propolis extract (PE) on colorectal cancer (CRC)using in vitro and in vivo studies. We exposed luciferase-transfected (Lovo-Luc CRC) cells and healthy colon cells (CCD-18Co) to varying concentrations of 5-FU and PE to assess their genotoxic, apoptotic, and cytotoxic effects, as well as their intracellular reactive oxygen species (iROS) levels. We also developed a xenograft model in nude mice and evaluated the anti-tumor effects of PE and 5-FU using various methods. Our findings showed that the combination of PE and 5-FU had selectivity against cancer cells, particularly at higher doses, and enhanced the anti-tumor effectiveness of 5-FU against colon CRC. The results suggest that PE can reduce side effects and increase the effectiveness of 5-FU through iROS generation in a dose-dependent manner.

Keywords: 5-fluorouracil; colorectal cancer; in vivo animal imaging system; propolis; xenograft models.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Colonic Neoplasms* / pathology
  • Colorectal Neoplasms* / drug therapy
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Mice
  • Mice, Nude
  • Propolis* / pharmacology
  • Propolis* / therapeutic use
  • Xenograft Model Antitumor Assays


  • Fluorouracil
  • Propolis