7-substituted coumarins inhibit proliferation and migration of laryngeal cancer cells in vitro

Anticancer Res. 2013 Oct;33(10):4347-56.

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).

Materials and 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.

Conclusion: Our findings suggest the therapeutic potential of 7-substituted coumarins in the treatment of laryngeal cancer.

Keywords: High-performance counter current chromatography; apoptosis; cell cycle; herniarin; laryngeal cancer cells; migration; proliferation; scoparone; umbelliferone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Chromatography, High Pressure Liquid
  • Coumarins / isolation & purification
  • Coumarins / pharmacology*
  • Fruit / chemistry
  • Heptanes / chemistry
  • Heracleum / chemistry
  • Humans
  • Laryngeal Neoplasms
  • Methanol / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Solvents / chemistry
  • Umbelliferones / isolation & purification
  • Umbelliferones / pharmacology*
  • Water / chemistry

Substances

  • Acetates
  • Antineoplastic Agents, Phytogenic
  • Coumarins
  • Heptanes
  • Plant Extracts
  • Solvents
  • Umbelliferones
  • Water
  • n-heptane
  • herniarin
  • 7-hydroxycoumarin
  • ethyl acetate
  • scoparone
  • Methanol