Geraniol, a component of plant essential oils, sensitizes human colonic cancer cells to 5-Fluorouracil treatment.
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.
Carnesecchi
S
S
Laboratory of Cancer Nutritional Prevention, Institut de Recherche contre les Cancers de l'Appareil Digestif, Strasbourg, France.
Langley
K
K
Exinger
F
F
Gosse
F
F
Raul
F
F
D000080462:Acyclic Monoterpenes; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D010938:Plant Oils / Q000737:chemistry*; D013729:Terpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000080462:Acyclic Monoterpenes; D000964:Antimetabolites, Antineoplastic; D010938:Plant Oils; D013729:Terpenes; C007836:geraniol; D005472:Fluorouracil