title: Geraniol, a component of plant essential oils, sensitizes human colonic cancer cells to 5-Fluorouracil treatment.
abstract: 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.
authors.affiliation: Laboratory of Cancer Nutritional Prevention, Institut de Recherche contre les Cancers de l'Appareil Digestif, Strasbourg, France.
authors.forename: S
authors.initials: S
authors.lastname: Carnesecchi
authors.forename: K
authors.initials: K
authors.lastname: Langley
authors.forename: F
authors.initials: F
authors.lastname: Exinger
authors.forename: F
authors.initials: F
authors.lastname: Gosse
authors.forename: F
authors.initials: F
authors.lastname: Raul
mesh_terms: 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
chemical_list: D000080462:Acyclic Monoterpenes; D000964:Antimetabolites, Antineoplastic; D010938:Plant Oils; D013729:Terpenes; C007836:geraniol; D005472:Fluorouracil