title: Liposomes modify the subcellular distribution of sclareol uptake by HCT-116 cancer cell lines.
abstract: The uptake of free and liposome-incorporated sclareol and its effect on the growth of human cancer cell line HCT-116 was investigated. Recovery of free and liposomal sclareol in cytosol, nuclei and crude membranes was monitored over time. HCT-116 cells were incubated with 100 microM of free or liposomal sclareol up to 96 h. Intact cells were subjected to subcellular fractionation in order to obtain highly purified fractions of nuclei, cytosol, and crude membranes. Sclareol was extracted from intact cells and from the subcellular fractions using the Bligh-Dyer method and was measured by HPTLC/FID. The effect of sclareol on cell growth was found time dependent. Free sclareol exhibited high toxicity, while the liposomal sclareol showed reduced cytotoxicity but retained the ability to reduce the cell growth rate. The uptake of sclareol by the cells was faster and higher compared to that of its liposomal form. The concentration of sclareol in the three subcellular fractions showed that liposomal sclareol is incorporated in crude membranes and from there it is released in cytosol and nuclei in a time dependent manner, while free sclareol passes directly in the cytosol. These results suggest that liposomal sclareol retains its growth inhibiting activity while its cytotoxic action is diminished. These findings could be due to the sustained delivery of sclareol to the different subcellular sites.
authors.affiliation: Ecole Pratique des Hautes Etudes, Section des Sciences de la Vie et de la Terre, En Sorbonne, Paris, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Paradissis
authors.forename: Sophia
authors.initials: S
authors.lastname: Hatziantoniou
authors.forename: Aristidis
authors.initials: A
authors.lastname: Georgopoulos
authors.forename: Anna-Maria G
authors.initials: AM
authors.lastname: Psarra
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Dimas
authors.forename: Costas
authors.initials: C
authors.lastname: Demetzos
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003600:Cytosol / Q000378:metabolism; D003692:Delayed-Action Preparations; D004224:Diterpenes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D008081:Liposomes; D013347:Subcellular Fractions; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004224:Diterpenes; D008081:Liposomes; C070760:sclareol