title: 7-substituted coumarins inhibit proliferation and migration of laryngeal cancer cells in vitro.
abstract: BACKGROUND
  Coumarins are a large group of naturally-occurring compounds with a wide range of biological properties, including anticancer activity. 7-Substituted coumarins (umbelliferone, scoparone, and herniarin) were analyzed for their potential anticancer activity against laryngeal cancer cells (LCC).
  
  
  METHODS
  High-performance counter-current chromatography was applied for successful separation of umbelliferone from fruits of Heracleum leskowii. A two-phase solvent system composed of n-heptane-methanol-ethyl acetate-water (1:2:1:2, v/v/v) was successfully used. Cell proliferation was assessed after 48-72 h by means of MTT test, and tumor cell motility by a wound assay model. Measurement of cell death was estimated using enzyme-linked immunosorbent assay (ELISA), and cell-cycle analysis was performed by flow cytometry. Extracellular signal-regulated kinases-1/2 (ERK1/2) and AKT kinase activation status were analyzed by western blotting.
  
  
  RESULTS
  Umbelliferone, scoparone, and, to a lesser extent, herniarin reduced viability and migration of RK33 LCC in a dose-dependent manner. Scoparone and herniarin were found to induce apoptosis of LCC. None of the tested compounds influenced the ERK1/2 and AKT kinase activity, nor significantly affected cell-cycle progression in the LCC line studied.
  
  
  CONCLUSIONS
  Our findings suggest the therapeutic potential of 7-substituted coumarins in the treatment of laryngeal cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Chodźki 1, 20-093 Lublin, Poland. michal.kielbus@umlub.pl.
authors.forename: Michal
authors.initials: M
authors.lastname: Kielbus
authors.forename: Krystyna
authors.initials: K
authors.lastname: Skalicka-Wozniak
authors.forename: Aneta
authors.initials: A
authors.lastname: Grabarska
authors.forename: Witold
authors.initials: W
authors.lastname: Jeleniewicz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dmoszynska-Graniczka
authors.forename: Andrew
authors.initials: A
authors.lastname: Marston
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Polberg
authors.forename: Piotr
authors.initials: P
authors.lastname: Gawda
authors.forename: Janusz
authors.initials: J
authors.lastname: Klatka
authors.forename: Andrzej
authors.initials: A
authors.lastname: Stepulak
mesh_terms: D000085:Acetates / Q000737:chemistry; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000302:isolation & purification / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D006536:Heptanes / Q000737:chemistry; D030002:Heracleum / Q000737:chemistry; D006801:Humans; D007822:Laryngeal Neoplasms; D000432:Methanol / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D012997:Solvents / Q000737:chemistry; D014468:Umbelliferones / Q000302:isolation & purification / Q000494:pharmacology*; D014867:Water / Q000737:chemistry
chemical_list: D000085:Acetates; D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D006536:Heptanes; D010936:Plant Extracts; D012997:Solvents; D014468:Umbelliferones; D014867:Water; C028618:n-heptane; C007929:herniarin; C031477:7-hydroxycoumarin; C007650:ethyl acetate; C018145:scoparone; D000432:Methanol
keywords: High-performance counter current chromatography; apoptosis; cell cycle; herniarin; laryngeal cancer cells; migration; proliferation; scoparone; umbelliferone