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

WEIZ G; GONZALEZ ALINA L; MANSILLA, IARA S; BRECCIA JAVIER D; MOLEJON, MARIA I

Congreso; Reunión Anual de Sociedades de Biociencias 2022; 2022

Liver cancer, more specifically hepatocellular carcinoma (HCC), is the second leading cause of cancer-related death and its incidence is increasing globally. We have recently reported that 4-methylumbelliferilrutinose (4MUR), an enzymatically synthetized compound, exhibit antitumoral effect on HCC. 4MUR could be used as HCC targeted therapy, without damaging non-tumoral cells or 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 compared with 4MU (p < 0.001). We next performed wound healing assays to examine the effect of the glycosylated drug on the migration of tumoral cells. 4MUR significantly inhibited the migration of Huh7 cells in a dose-dependent manner compared to the untreated group. Based on the evidence that hyaluronic acid (HA) and its receptors play an important role in tumor migration we quantified by RT-PCR the HA synthases (HAS2 and HAS3) and HA-receptor expression. In Huh7 cells, the expression of HAS2 was significantly reduced upon 4MUR treatment (p