4-Methylumbelliferone exerts anti-tumor effects in an independent manner to hyaluronan synthesis inhibition in human glioblastoma cells.

POODTS DANIELA; ÁLVAREZ ÉLIDA; DÍAZ MARIÁNGELES; LOMPARDÍA SILVINA; PIBUEL MATÍAS; HAJOS SILVIA E.

Cardiff

Congreso; Hyaluronan Meeting 2019; 2019

ISHAS

4-methylumbelliferone (4MU) is a coumarin derivative without reported adverse effects, that shows anti-tumoral effects on several neoplasms. Despite being widely used as hyaluronan (HA) synthesis inhibitor, HA-independent effects have been recently reported. HA is the main glycosaminoglycan of extracellular matrix and it is strongly involved in tumor progression, favoring cell proliferation and migration, processes that are directly related with glioblastoma, the most common primary tumor of the central nervous system. Given that current therapy for this type of cancer is ineffective and highly toxic, new drugs are required for glioblastoma treatment. Our hypothesis is that 4MU exerts anti-tumoral effects on glioblastoma as a consequence of independent mechanisms of hyaluronan synthesis. Therefore, the aim of this work was to evaluate the effect of HA, 4MU and their combination on cell migration and metabolic as well as metalloprotease (MMP) activity in LN229 and U251 human glioblastoma cell lines. Metabolic activity was evaluated by XTT assay, migration by wound healing assay, MMPs activity by zymography and cell death by FDA/PI using flow cytometry. 4MU reduced metabolic activity in a dose-dependent manner in both cell lines (p