ANTICANCER EFFECTS OF GLYCOSYLATED 4-METHYLUMBELLIFERONE ON HEPATOCELLULAR CARCINOMA THROUGH REGULATION OF APOPTOSIS AND MIGRATION

WEIZ G; GONZALEZ A; MANSILLA I; BRECCIA J; MOLEJON, MI

Congreso; Reunion Anual de Sociedades deBiociencias; 2022

Liver cancer, more specifically hepatocellular carcinoma (HCC), is the second leading cause ofcancer-related death and its incidence is increasing globally. We have recently reported that 4-methylumbelliferilrutinose (4MUR), an enzymatically synthetized compound, exhibit antitumoraleffect on HCC. 4MUR could be used as HCC targeted therapy, without damaging non-tumoral cellsor other organs. In this work we aim to understand the molecular processes involved in 4MUR-related antitumor efficacy. First, we evaluated its effect on cell death using HCC tumoral cell lines.The percentage of apoptotic Huh7 cells exposed to 4MUR significantly increased as comparedwith 4MU (p < 0.001). We next performed wound healing assays to examine the effect of theglycosylated drug on the migration of tumoral cells. 4MUR significantly inhibited the migration ofHuh7 cells in a dose-dependent manner compared to the untreated group. Based on the evidencethat hyaluronic acid (HA) and its receptors play an important role in tumor migration we quantifiedby RT-PCR the HA synthases (HAS2 and HAS3) and HA-receptor expression. In Huh7 cells, theexpression of HAS2 was significantly reduced upon 4MUR treatment (p