Geraniol, a component of plant essential oils, sensitizes human colonic cancer cells to 5-Fluorouracil treatment

J Pharmacol Exp Ther. 2002 May;301(2):625-30. doi: 10.1124/jpet.301.2.625.


Differentiation of human colonic cancer cells at confluency has been correlated to their increased resistance to chemotherapeutic agents. The aim of this study was to determine whether blocking Caco-2 cell differentiation could sensitize the cells to 5-fluorouracil (5-FU) treatment. We show that in cells at confluency, geraniol (400 microM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase). The antiproliferative effect of geraniol (400 microM) together with 5-FU (5 microM) was twice that of 5-FU alone. The cytotoxicity induced by 5-FU was enhanced in the presence of geraniol, as shown by a 50% increase of lactate dehydrogenase release in the culture medium. These effects are related to enhanced intracellular accumulation of 5-FU in the presence of geraniol as shown by a 2-fold increase in intracellular 5-[6-(3)H]FU (1.5 microCi/ml). It is concluded that geraniol sensitizes colonic cancer cells to 5-FU treatment, by increasing the cytotoxicity of the drug, and that this results from the facilitated transport of 5-FU and the blockade of the morphological and functional differentiation of the cancer cells.

MeSH terms

  • Acyclic Monoterpenes
  • Antimetabolites, Antineoplastic / pharmacology*
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Cell Death / drug effects
  • Cell Differentiation / drug effects*
  • Cell Division / drug effects
  • Colonic Neoplasms
  • Drug Resistance, Neoplasm
  • Drug Synergism
  • Fluorouracil / pharmacology*
  • Humans
  • Plant Oils / chemistry*
  • Terpenes / pharmacology*
  • Tumor Cells, Cultured


  • Acyclic Monoterpenes
  • Antimetabolites, Antineoplastic
  • Plant Oils
  • Terpenes
  • geraniol
  • Fluorouracil