title: In vitro antileukaemic activity of extracts from Daphne gnidium leaves against sensitive and multidrug resistant K562/R7 cells.
abstract: The antiproliferative potential of extracts of Daphne gnidium L. (Thymelaeaceae) on K562 cells was assessed, and the capacity of these extracts to disturb the cell cycle of K562 cells and to inhibit human P-glycoprotein was evaluated. The antiproliferative activity was evaluated using the MTT assay. The cell cycle analysis and the inhibition of P-glycoprotein were tested by flow cytometry. All the tested extracts exhibited significant anti-proliferative effects. Ethyl acetate extract has the strongest cytotoxic effect with an IC50 of 18.5 μg/ml. Furthermore, cell cycle analysis revealed that cells treated with chloroform, butanol and aqueous extracts were arrested predominantly in G2-M phase. Butanol extract was the most active extract. Percentage of cells arrested in G2-M was 34 %, 36.67 % and 42.63 % respectively, after treatment with 25, 75 and 100 μg/ml of the extract, versus 19 % in the cells treated with the vehicle solvent. In addition, chloroform extract had the ability to inhibit human P-glycoprotein-mediated daunorubicin in K562/R7 leukaemic cells in a dose-dependent manner compared to the positive control, cyclosporin A. These findings demonstrate that extracts from D. gnidium leaves have antileukaemic activity by perturbing the cell cycle of K562 and inhibiting human P-glycoprotein in K562/R7 cell line.
authors.affiliation: Unité de Substances Naturelles Bioactives et Biotechnologie UR12ES12, Faculté de Pharmacie de Monastir, Université de Monastir, Monastir, Tunisie.
authors.forename: Fadwa
authors.initials: F
authors.lastname: Chaabane
authors.forename: Mounira
authors.initials: M
authors.lastname: Krifa
authors.forename: Eva
authors.initials: E
authors.lastname: Matera
authors.forename: Amira
authors.initials: A
authors.lastname: Loussaeif
authors.forename: Marie-Geneviève
authors.initials: MG
authors.lastname: Dijoux-Franca
authors.forename: Kamel
authors.initials: K
authors.lastname: Ghedira
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Leila
authors.initials: L
authors.lastname: Chekir-Ghedira
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000378:metabolism; D000085:Acetates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000440:Butanols / Q000737:chemistry; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D032364:Daphne / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects; D005419:Flavonoids / Q000032:analysis; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*; D059808:Polyphenols / Q000032:analysis; D012997:Solvents / Q000737:chemistry
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000085:Acetates; D000970:Antineoplastic Agents; D000440:Butanols; D005419:Flavonoids; D010936:Plant Extracts; D059808:Polyphenols; D012997:Solvents; C007650:ethyl acetate