Enhanced antitumoral effect of the glycosylated 4-methylumbelliferone in hepatocellular carcinoma

GISELA WEIZ; ALINA GONZALEZ; FLAVIA PICCIONI; MARIEL FUSCO; MARCO AURELIO DIAZ GUTIERREZ; GUILLERMO MAZZOLINI; JAVIER BRECCIA; MARIANA MALVICINI; MARIA INES MOLEJON

Congreso; AACR Annual Meeting 2022; 2022

AACR

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide, and is particularly refractory to the available therapeutic drugs. Unfortunately, curative treatments such as surgery, liver transplantation, or ablation are reserved for early stages and can only be applied in less than 30% of the patients with HCC. Glycosylation can be a potent and interesting strategy for drug delivery to a specific target. We enzymatically synthesized a glycosylated derivative of the coumarin 4-methylumbelliferone (4MU), namely 4MUR.The antitumoral effect of 4MUR in comparison with the aglycone 4MU was evaluated onto liver cancer cells. Cellular toxicity was determined on murine liver tumor cell lines as well as non-hepatic tumoral cells. Tumor cell lines were significantly more sensitive than non-tumoral cells to the glycosylated molecule in a dose-dependent manner (p