7-substituted coumarins inhibit proliferation and migration of laryngeal cancer cells in vitro.
Michal Kielbus, Krystyna Skalicka-Wozniak, Aneta Grabarska, Witold Jeleniewicz, Magdalena Dmoszynska-Graniczka, Andrew Marston, Krzysztof Polberg, Piotr Gawda, Janusz Klatka, Andrzej Stepulak
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).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.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.Our findings suggest the therapeutic potential of 7-substituted coumarins in the treatment of laryngeal cancer.
