PT  - JOURNAL ARTICLE
AU  - S. Carnesecchi
AU  - K. Langley
AU  - F. Exinger
AU  - F. Gosse
AU  - F. Raul
TI  - Geraniol, a Component of Plant Essential Oils, Sensitizes Human Colonic Cancer Cells to 5-Fluorouracil Treatment
AID  - 10.1124/jpet.301.2.625
DP  - 2002 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 625--630
VI  - 301
IP  - 2
4099  - http://jpet.aspetjournals.org/content/301/2/625.short
4100  - http://jpet.aspetjournals.org/content/301/2/625.full
SO  - J Pharmacol Exp Ther2002 May 01; 301
AB  - 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 μM) prevented the formation of brush-border membranes and inhibited the expression of intestinal hydrolases (sucrase, lactase, alkaline phosphatase). The antiproliferative effect of geraniol (400 μM) together with 5-FU (5 μM) 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-[6-3H]FU (1.5 μCi/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. The American Society for Pharmacology and Experimental Therapeutics