title: The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata             inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis.
abstract: The present study investigates extracts of Neuolaena lobata, an anti-protozoan             ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly,             extracts of increasing polarity were tested in HL-60 cells analyzing inhibition             of cell proliferation and apoptosis induction. Secondly, the most active extract             was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human             and mouse origin. The dichloromethane extract inhibited proliferation of HL-60,             human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively             and arrested cells in the G2/M phase. The extract induced the checkpoint kinases             Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of             cell cycle phosphatases which was paralleled by the activation of p53, p21 and             downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector             JunB were drastically decreased, which correlated with the activation of caspase             3. Subsequently also platelet derived growth factor receptor β was downregulated,             which was recently shown to be transcriptionally controlled by JunB synergizing             with ALK in ALCL development. We show that a traditional healing plant extract             downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation             and triggers apoptosis of malignant cells. The discovery of the 'Active Principle(s)'             is warranted.
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna,                     Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Unger
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Popescu
authors.forename: Benedikt
authors.initials: B
authors.lastname: Giessrigl
authors.forename: Daniela
authors.initials: D
authors.lastname: Laimer
authors.forename: Susanne
authors.initials: S
authors.lastname: Heider
authors.forename: Mareike
authors.initials: M
authors.lastname: Seelinger
authors.forename: Rene
authors.initials: R
authors.lastname: Diaz
authors.forename: Bruno
authors.initials: B
authors.lastname: Wallnöfer
authors.forename: Gerda
authors.initials: G
authors.lastname: Egger
authors.forename: Melanie
authors.initials: M
authors.lastname: Hassler
authors.forename: Martin
authors.initials: M
authors.lastname: Knöfler
authors.forename: Leila
authors.initials: L
authors.lastname: Saleh
authors.forename: Emine
authors.initials: E
authors.lastname: Sahin
authors.forename: Michael
authors.initials: M
authors.lastname: Grusch
authors.forename: Monika
authors.initials: M
authors.lastname: Fritzer-Szekeres
authors.forename: Helmut
authors.initials: H
authors.lastname: Dolznig
authors.forename: Richard
authors.initials: R
authors.lastname: Frisch
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kopp
authors.forename: Georg
authors.initials: G
authors.lastname: Krupitza
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019659:Asteraceae / Q000737:chemistry*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008752:Methylene Chloride / Q000737:chemistry*; D051379:Mice; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D010936:Plant Extracts; D008752:Methylene Chloride; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases